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Conserved domains on  [gi|307167498|gb|EFN61071|]
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1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1 [Camponotus floridanus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 93-256 8.61e-102

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


:

Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 317.83  E-value: 8.61e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08592    2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKKLpdGVDESSFLVRN 252
Cdd:cd08592   82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKRKIIIKHKKL--FYEMSSFPETK 159


                 ....
gi 307167498 253 DESR 256
Cdd:cd08592  160 AEKY 163
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 439-542 4.81e-64

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198186  Cd Length: 104  Bit Score: 210.97  E-value: 4.81e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 439 HEEKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTTGTVQFESLVELINYY 518
Cdd:cd09932    1 HESKEWFHANLTREQAEEMLMRVPRDGAFLVRPSETDPNSFAISFRAEGKIKHCRIKQEGRLFVIGTSQFESLVELVSYY 80

                         90       100
                 ....*....|....*....|....
gi 307167498 519 ERRPLYKKIKLSHPVNQDIIRRMG 542
Cdd:cd09932   81 EKHPLYRKIKLRYPVNEELLEKYG 104
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 710-825 1.35e-59

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to form a single structural unit.


:

Pssm-ID: 459794  Cd Length: 114  Bit Score: 198.84  E-value: 1.35e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  710 MSNLIVYCRSVAF-NIERIRTKgfTFNEMSSFPETKAEKLmCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNA 788
Cdd:pfam00387   1 LSDLVVYTQSVKFkSFSTPESK--TPNHIFSFSESKALKL-IKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNC 77

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 307167498  789 GCQMVALNYQTGDKSMQLNQAKFKENGNCGYLLKPEF 825
Cdd:pfam00387  78 GVQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 845-968 1.39e-52

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


:

Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 179.66  E-value: 1.39e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 845 LKICLKVIGARHLMKSG---RGTASPSIEVEIIGADFDSGTKLTTKTIPDNGFNPMWNETCEFEIFNPYFALIRFLVQDE 921
Cdd:cd00275    2 LTLTIKIISGQQLPKPKgdkGSIVDPYVEVEIHGLPADDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDE 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 307167498 922 DMFGDsNFIGQATYPVRCLRTGYRSVPLKNVYSEDLELASLLVHIKI 968
Cdd:cd00275   82 DSGDD-DFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDI 127
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 327-425 3.83e-50

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 199829  Cd Length: 99  Bit Score: 171.77  E-value: 3.83e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 327 HFGEKWFHGKLARGREEAEELLRHYSYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGQTQYYLIDTNCFD 406
Cdd:cd10341    1 HFTEPWFHGKLGDGRDEAEKLLLEYCEGGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQENGEKKYYLTDNLVFD 80

                         90
                 ....*....|....*....
gi 307167498 407 SLYSLITHYRNHPLRSQEF 425
Cdd:cd10341   81 SLYELIDYYRQNPLRCAEF 99
EFh_PI-PLC super family cl28895
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 1-80 3.80e-30

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


The actual alignment was detected with superfamily member cd16201:

Pssm-ID: 333715 [Multi-domain]  Cd Length: 145  Bit Score: 116.52  E-value: 3.80e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   1 MFDQNNLADWHKLLNYSQIEPTVTLQEFQNFLLTEQQDSLGNNELEISRFIREYLQDPQRDIQEPYFTFSEFVDFLFSKQ 80
Cdd:cd16201   66 MFDQKIIEDFFKKYSYSSDGQTVTLEDFQRFLLEEQKEPWANDPNAVREFMRDFLQDPLRDVQEPYFTLDEFLDYLFSKE 145
SH3 super family cl17036
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
 562-610 7.12e-24

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


The actual alignment was detected with superfamily member cd11825:

Pssm-ID: 473055 [Multi-domain]  Cd Length: 54  Bit Score: 95.09  E-value: 7.12e-24
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYVEE 610
Cdd:cd11825    6 YDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKKQKWFPANYVEE 54
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 266-296 3.57e-09

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13234:

Pssm-ID: 473070  Cd Length: 105  Bit Score: 55.17  E-value: 3.57e-09
                         10        20        30
                 ....*....|....*....|....*....|.
gi 307167498 266 KNGILYLEDPIDKEWNPHFFVLTQQKLFYTD 296
Cdd:cd13234    3 KNGILYLEDPINHEWYPHFFVLTSNKIYYSE 33
 
Name Accession Description Interval E-value
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 93-256 8.61e-102

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 317.83  E-value: 8.61e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08592    2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKKLpdGVDESSFLVRN 252
Cdd:cd08592   82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKRKIIIKHKKL--FYEMSSFPETK 159


                 ....
gi 307167498 253 DESR 256
Cdd:cd08592  160 AEKY 163
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 95-236 9.22e-81

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit.


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 258.20  E-value: 9.22e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   95 MARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKEHA 174
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 307167498  175 FATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKH 236
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPEDLKGKILIKG 142
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 95-237 1.30e-67

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 222.16  E-value: 1.30e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498    95 MARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKEHA 174
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 307167498   175 FATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHK 237
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQLRGKILLKVR 143
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 439-542 4.81e-64

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 210.97  E-value: 4.81e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 439 HEEKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTTGTVQFESLVELINYY 518
Cdd:cd09932    1 HESKEWFHANLTREQAEEMLMRVPRDGAFLVRPSETDPNSFAISFRAEGKIKHCRIKQEGRLFVIGTSQFESLVELVSYY 80

                         90       100
                 ....*....|....*....|....
gi 307167498 519 ERRPLYKKIKLSHPVNQDIIRRMG 542
Cdd:cd09932   81 EKHPLYRKIKLRYPVNEELLEKYG 104
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 710-825 1.35e-59

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to form a single structural unit.


Pssm-ID: 459794  Cd Length: 114  Bit Score: 198.84  E-value: 1.35e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  710 MSNLIVYCRSVAF-NIERIRTKgfTFNEMSSFPETKAEKLmCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNA 788
Cdd:pfam00387   1 LSDLVVYTQSVKFkSFSTPESK--TPNHIFSFSESKALKL-IKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNC 77

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 307167498  789 GCQMVALNYQTGDKSMQLNQAKFKENGNCGYLLKPEF 825
Cdd:pfam00387  78 GVQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 711-826 8.84e-55

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 128454 [Multi-domain]  Cd Length: 115  Bit Score: 185.52  E-value: 8.84e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   711 SNLIVYCRSVAFNIERIRTKGFTFNEMSSFPETKAEKLMcQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGC 790
Cdd:smart00149   1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLL-KKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGC 79

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 307167498   791 QMVALNYQTGDKSMQLNQAKFKENGNCGYLLKPEFM 826
Cdd:smart00149  80 QMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 845-968 1.39e-52

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 179.66  E-value: 1.39e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 845 LKICLKVIGARHLMKSG---RGTASPSIEVEIIGADFDSGTKLTTKTIPDNGFNPMWNETCEFEIFNPYFALIRFLVQDE 921
Cdd:cd00275    2 LTLTIKIISGQQLPKPKgdkGSIVDPYVEVEIHGLPADDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDE 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 307167498 922 DMFGDsNFIGQATYPVRCLRTGYRSVPLKNVYSEDLELASLLVHIKI 968
Cdd:cd00275   82 DSGDD-DFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDI 127
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 327-425 3.83e-50

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 171.77  E-value: 3.83e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 327 HFGEKWFHGKLARGREEAEELLRHYSYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGQTQYYLIDTNCFD 406
Cdd:cd10341    1 HFTEPWFHGKLGDGRDEAEKLLLEYCEGGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQENGEKKYYLTDNLVFD 80

                         90
                 ....*....|....*....
gi 307167498 407 SLYSLITHYRNHPLRSQEF 425
Cdd:cd10341   81 SLYELIDYYRQNPLRCAEF 99
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 734-814 2.94e-46

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 165.68  E-value: 2.94e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 734 FNEMSSFPETKAEKLMCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKE 813
Cdd:cd08592  149 FYEMSSFPETKAEKYLNRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFML 228


                 .
gi 307167498 814 N 814
Cdd:cd08592  229 N 229
PLN02952 PLN02952
phosphoinositide phospholipase C
 739-964 9.15e-34

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 138.21  E-value: 9.15e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 739 SFPETKAEKlMCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKENGNCG 818
Cdd:PLN02952 364 SLSEQELEK-AATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCG 442

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 819 YLLKPEFMFRQDFNP--YD-KNTLYGVESLKIclKVI---GAR-HLMKSGRGTASPS---IEVEIIGADFDSGTKlTTKT 888
Cdd:PLN02952 443 YLKKPDFLMKKGFHDevFDpKKKLPVKKTLKV--KVYlgdGWRlDFSHTHFDSYSPPdfyTKMYIVGVPADNAKK-KTKI 519

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 307167498 889 IPDNgFNPMWNETCEFEIFNPYFALIRFLVQDEDMFGDSNFIGQATYPVRCLRTGYRSVPLKNVYSEDLELASLLV 964
Cdd:PLN02952 520 IEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLM 594
PLN02952 PLN02952
phosphoinositide phospholipase C
 23-237 1.50e-33

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 137.44  E-value: 1.50e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  23 VTLQEFQNFLLtEQQDSLGNNELEISRFIREYLQdpQRDIQEPY----FTFSEFVDFLFskQNDIWNQKFNQVSQDMARP 98
Cdd:PLN02952  54 MGADQLRRFLV-LHQDELDCTLAEAQRIVEEVIN--RRHHVTRYtrhgLNLDDFFHFLL--YDDLNGPITPQVHHDMTAP 128

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  99 LAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMP-FIFHGHTLTTKIKFLDVIKTIKEHAFAT 177
Cdd:PLN02952 129 LSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEiLVLHGRTLTTPVPLIKCLKSIRDYAFSS 208

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 178 SEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVqPVDKNETCLPSPYAMRRKILLKHK 237
Cdd:PLN02952 209 SPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYY-PESDSLVQFPSPESLKHRIIISTK 267
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
 1-80 3.80e-30

EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); PI-PLC-gamma isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. They can form a complex with the phosphorylated cytoplasmic domains of the immunoglobulin Ig-alpha and Ig-beta subunits of the B cell receptor (BCR), the membrane-tethered Src family kinase Lyn, phosphorylated spleen tyrosine kinase (Syk), the phosphorylated adaptor protein B-cell linker (BLNK), and activated Bruton's tyrosine kinase (Btk). Like other PI-PLC isozymes, PI-PLC-gamma isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker. The SH2 and SH3 domains are responsible for the binding of phosphotyrosine-containing sequences and proline-rich sequences, respectively. There are two PI-PLC-gamma isozymes (1-2), both of which are activated by receptor and non-receptor tyrosine kinases due to the presence of SH2 and SH3 domains.


Pssm-ID: 320031 [Multi-domain]  Cd Length: 145  Bit Score: 116.52  E-value: 3.80e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   1 MFDQNNLADWHKLLNYSQIEPTVTLQEFQNFLLTEQQDSLGNNELEISRFIREYLQDPQRDIQEPYFTFSEFVDFLFSKQ 80
Cdd:cd16201   66 MFDQKIIEDFFKKYSYSSDGQTVTLEDFQRFLLEEQKEPWANDPNAVREFMRDFLQDPLRDVQEPYFTLDEFLDYLFSKE 145
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
 562-610 7.12e-24

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212759 [Multi-domain]  Cd Length: 54  Bit Score: 95.09  E-value: 7.12e-24
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYVEE 610
Cdd:cd11825    6 YDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKKQKWFPANYVEE 54
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 330-421 1.70e-23

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 94.99  E-value: 1.70e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   330 EKWFHGKLarGREEAEELLRHYsylGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKlKQEMGqtQYYLIDTNCFDSLY 409
Cdd:smart00252   1 QPWYHGFI--SREEAEKLLKNE---GDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIR-RNEDG--KFYLEGGRKFPSLV 72

                           90
                   ....*....|..
gi 307167498   410 SLITHYRNHPLR 421
Cdd:smart00252  73 ELVEHYQKNSLG 84
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 443-524 9.08e-23

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 93.06  E-value: 9.08e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   443 EWWHPECTRIAAEEMLKRIPtDGAFLVRPSERESNCYAISFRAEKKIKHCKIKL--EGRLYTTGTVQFESLVELINYYER 520
Cdd:smart00252   2 PWYHGFISREEAEKLLKNEG-DGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRneDGKFYLEGGRKFPSLVELVEHYQK 80


                   ....
gi 307167498   521 RPLY 524
Cdd:smart00252  81 NSLG 84
SH2 pfam00017
SH2 domain;
332-415 2.46e-22

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 91.51  E-value: 2.46e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  332 WFHGKLarGREEAEELLRhySYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIklkQEMGQTQYYLIDTNCFDSLYSL 411
Cdd:pfam00017   1 WYHGKI--SRQEAERLLL--NGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKI---QSTDNGGYYISGGVKFSSLAEL 73


                  ....
gi 307167498  412 ITHY 415
Cdd:pfam00017  74 VEHY 77
SH2 pfam00017
SH2 domain;
444-518 1.22e-21

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 89.58  E-value: 1.22e-21
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498  444 WWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIK--LEGRLYTTGTVQFESLVELINYY 518
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQstDNGGYYISGGVKFSSLAELVEHY 77
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 846-949 2.87e-18

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 80.99  E-value: 2.87e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   846 KICLKVIGARHLM-KSGRGTASPSIEVEIIGADfdsGTKLTTKTIPDNGfNPMWNETCEFEIFNPYFALIRFLVQDEDMF 924
Cdd:smart00239   1 TLTVKIISARNLPpKDKGGKSDPYVKVSLDGDP---KEKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*
gi 307167498   925 GDSNFIGQATYPVRCLRTGYRSVPL 949
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
846-945 7.15e-17

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 76.97  E-value: 7.15e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  846 KICLKVIGARHLM-KSGRGTASPSIEVEIIgadfDSGTKLTTKTIpDNGFNPMWNETCEFEIFNPYFALIRFLVQDEDMF 924
Cdd:pfam00168   2 RLTVTVIEAKNLPpKDGNGTSDPYVKVYLL----DGKQKKKTKVV-KNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRF 76

                          90       100
                  ....*....|....*....|.
gi 307167498  925 GDSNFIGQATYPVRCLRTGYR 945
Cdd:pfam00168  77 GRDDFIGEVRIPLSELDSGEG 97
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 565-609 8.38e-10

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 55.24  E-value: 8.38e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 307167498   565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYVE 609
Cdd:smart00326  12 TAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56
PHsplit_PLC_gamma cd13234
Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...
 266-296 3.57e-09

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. The split PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270054  Cd Length: 105  Bit Score: 55.17  E-value: 3.57e-09
                         10        20        30
                 ....*....|....*....|....*....|.
gi 307167498 266 KNGILYLEDPIDKEWNPHFFVLTQQKLFYTD 296
Cdd:cd13234    3 KNGILYLEDPINHEWYPHFFVLTSNKIYYSE 33
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 565-605 1.05e-06

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 46.04  E-value: 1.05e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 307167498  565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPA 605
Cdd:pfam00018   7 TAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGGKEGLIPS 47
 
Name Accession Description Interval E-value
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 93-256 8.61e-102

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 317.83  E-value: 8.61e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08592    2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKKLpdGVDESSFLVRN 252
Cdd:cd08592   82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKRKIIIKHKKL--FYEMSSFPETK 159


                 ....
gi 307167498 253 DESR 256
Cdd:cd08592  160 AEKY 163
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 93-238 9.06e-94

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; This family corresponds to the catalytic domain present in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) and similar proteins. The higher eukaryotic PI-PLCs play a critical role in most signal transduction pathways, controlling numerous cellular events such as cell growth, proliferation, excitation and secretion. They strictly require Ca2+ for the catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated membrane phospholipids PI-analogues, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP), to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. The eukaryotic PI-PLCs have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains, such as the pleckstrin homology (PH) domain, EF-hand motif, and C2 domain. The catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a linker region. The catalytic mechanism of eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. The mammalian PI-PLCs consist of 13 isozymes, which are classified into six-subfamilies, PI-PLC-delta (1,3 and 4), -beta(1-4), -gamma(1,2), -epsilon, -zeta, and -eta (1,2). Ca2+ is required for the activation of all forms of mammalian PI-PLCs, and the concentration of calcium influences substrate specificity. This family also includes metazoan phospholipase C related but catalytically inactive proteins (PRIP), which belong to a group of novel inositol trisphosphate binding proteins. Due to the replacement of critical catalytic residues, PRIP does not have PLC enzymatic activity.


Pssm-ID: 176501 [Multi-domain]  Cd Length: 226  Bit Score: 296.28  E-value: 9.06e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08558    2 QDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIKE 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKK 238
Cdd:cd08558   82 YAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENPVQLPSPEQLKGKILIKGKK 147
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 93-248 5.45e-83

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma1, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma1 is ubiquitously expressed. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region.


Pssm-ID: 176564 [Multi-domain]  Cd Length: 229  Bit Score: 267.66  E-value: 5.45e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08627    2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKKLPDgvDESSF 248
Cdd:cd08627   82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPVDINADGLPSPNQLKRKILIKHKKLYR--DMSSF 155
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 93-239 2.29e-81

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. Aside from three PI-PLC-delta isozymes identified in mammals, some eukaryotic PI-PLC-delta homologs have been classified to this CD.


Pssm-ID: 176535 [Multi-domain]  Cd Length: 257  Bit Score: 264.20  E-value: 2.29e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08593    2 QDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIRE 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKKL 239
Cdd:cd08593   82 YAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVLTALPSPEELKGKILVKGKKL 148
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 95-236 9.22e-81

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit.


Pssm-ID: 459795 [Multi-domain]  Cd Length: 142  Bit Score: 258.20  E-value: 9.22e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   95 MARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKEHA 174
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 307167498  175 FATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKH 236
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPEDLKGKILIKG 142
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 93-239 1.67e-73

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 2. PI-PLC is a signaling enzyme that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma2, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma2 is highly expressed in cells of hematopoietic origin. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.


Pssm-ID: 176565 [Multi-domain]  Cd Length: 254  Bit Score: 243.04  E-value: 1.67e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08628    2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKKL 239
Cdd:cd08628   82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEASADQLPSPTQLKEKIIIKHKKL 148
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 92-264 1.70e-70

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this CD is protein Plc1p encoded by PLC1 genes from Saccharomyces cerevisiae. Plc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that Plc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like Plc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 176540 [Multi-domain]  Cd Length: 231  Bit Score: 233.68  E-value: 1.70e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  92 SQDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIK 171
Cdd:cd08598    1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 172 EHAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKKLPD------GVDE 245
Cdd:cd08598   81 KYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDGLEDELPSPEELRGKILIKVKKESKtpnhifSLSE 160

                        170
                 ....*....|....*....
gi 307167498 246 SSFLVRNDESRQEMDLRNT 264
Cdd:cd08598  161 RSLLKLLKDKRAALDKHNR 179
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 93-239 1.14e-69

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This family corresponds to the catalytic domain present in metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel Inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(previously known as p130 or PLC-1), which is predominantly expressed in the brain, and PRIP-2 (previously known as PLC-2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses.


Pssm-ID: 176539 [Multi-domain]  Cd Length: 260  Bit Score: 232.70  E-value: 1.14e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08597    2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKKL 239
Cdd:cd08597   82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGESYLPSPHDLKGKIIIKGKKL 148
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 95-237 1.30e-67

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 222.16  E-value: 1.30e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498    95 MARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKEHA 174
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 307167498   175 FATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHK 237
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQLRGKILLKVR 143
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 93-239 6.44e-67

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta1 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This subfamily corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1and 3 from the cell nucleus. Experiments show PI-PLC-delta1 is essential for normal hair formation.


Pssm-ID: 176566 [Multi-domain]  Cd Length: 258  Bit Score: 224.91  E-value: 6.44e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08629    2 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIRD 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKKL 239
Cdd:cd08629   82 YAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDGVTTSLPSPEQLKGKILLKGKKL 148
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 93-238 1.67e-65

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are two PI-PLC-eta isozymes (1-2), both neuron-specific enzymes. They function as calcium sensors that are activated by small increases in intracellular calcium concentrations. The PI-PLC-eta isozymes are also activated through GPCR stimulation. Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 176536 [Multi-domain]  Cd Length: 227  Bit Score: 219.67  E-value: 1.67e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08594    2 QDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETINK 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNE-TCLPSPYAMRRKILLKHKK 238
Cdd:cd08594   82 YAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGDsKQLPSPQSLKGKILIKGKK 148
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 92-243 2.24e-65

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PLC-beta isozymes (1-4). They are activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. The beta-gamma subunits of heterotrimeric G proteins are known to activate the PLC-beta2 and -beta3 isozymes only. Aside from four PLC-beta isozymes identified in mammals, some eukaryotic PLC-beta homologs have been classified into this subfamily, such as NorpA and PLC-21 from Drosophila and PLC-beta from turkey, Xenopus, sponge, and hydra.


Pssm-ID: 176533 [Multi-domain]  Cd Length: 257  Bit Score: 220.67  E-value: 2.24e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  92 SQDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDG--PDGMPFIFHGHTLTTKIKFLDVIKT 169
Cdd:cd08591    1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 170 IKEHAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNE----TCLPSPYAMRRKILLKHKKLPDGV 243
Cdd:cd08591   81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPlepgVPLPSPNDLKRKILIKNKKLSSLV 158
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 439-542 4.81e-64

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 210.97  E-value: 4.81e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 439 HEEKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTTGTVQFESLVELINYY 518
Cdd:cd09932    1 HESKEWFHANLTREQAEEMLMRVPRDGAFLVRPSETDPNSFAISFRAEGKIKHCRIKQEGRLFVIGTSQFESLVELVSYY 80

                         90       100
                 ....*....|....*....|....
gi 307167498 519 ERRPLYKKIKLSHPVNQDIIRRMG 542
Cdd:cd09932   81 EKHPLYRKIKLRYPVNEELLEKYG 104
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 93-239 1.52e-63

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta3 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This family corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus.


Pssm-ID: 176567 [Multi-domain]  Cd Length: 258  Bit Score: 215.66  E-value: 1.52e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08630    2 QDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVRQ 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDK-NETCLPSPYAMRRKILLKHKKL 239
Cdd:cd08630   82 HAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSlNPEELPSPEELKGRVLVKGKKL 149
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 93-244 8.14e-63

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-epsilon isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-epsilon represents a class of mammalian PI-PLC that has an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and two predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PI-PLC-epsilon isozyme (1). PI-PLC-epsilon is activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Aside from PI-PLC-epsilon identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176538 [Multi-domain]  Cd Length: 254  Bit Score: 213.56  E-value: 8.14e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08596    2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDML----LVQPVDKNETCLPSPYAMRRKILLKHKKLPDGVD 244
Cdd:cd08596   82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLvtkfLFESDFSDDPSLPSPLQLKNKILLKNKKAPELSD 157
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 92-267 6.96e-62

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta2 is a neuron-specific enzyme and expressed in the brain. It may in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain.


Pssm-ID: 176570 [Multi-domain]  Cd Length: 254  Bit Score: 210.67  E-value: 6.96e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  92 SQDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIK 171
Cdd:cd08633    1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 172 EHAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNE-TCLPSPYAMRRKILLKHKKLPDGVDEssfLV 250
Cdd:cd08633   81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDcTRLPSPEILKGKILVKGKKLSRALSD---LV 157

                        170
                 ....*....|....*..
gi 307167498 251 RNDESRQEMDLRNTVKN 267
Cdd:cd08633  158 KYTKSVRVHDIETEATS 174
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 93-239 1.13e-61

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta4 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4. Experiments show PI-PLC-delta4 is required for the acrosome reaction in fertilization.


Pssm-ID: 176568 [Multi-domain]  Cd Length: 258  Bit Score: 210.19  E-value: 1.13e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08631    2 QDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVAQ 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVD-KNETCLPSPYAMRRKILLKHKKL 239
Cdd:cd08631   82 YAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDgVLPTQLPSPEELRGKILLKGKKI 149
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 710-825 1.35e-59

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to form a single structural unit.


Pssm-ID: 459794  Cd Length: 114  Bit Score: 198.84  E-value: 1.35e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  710 MSNLIVYCRSVAF-NIERIRTKgfTFNEMSSFPETKAEKLmCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNA 788
Cdd:pfam00387   1 LSDLVVYTQSVKFkSFSTPESK--TPNHIFSFSESKALKL-IKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNC 77

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 307167498  789 GCQMVALNYQTGDKSMQLNQAKFKENGNCGYLLKPEF 825
Cdd:pfam00387  78 GVQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 93-239 8.07e-59

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta1 is a neuron-specific enzyme and expressed in only nerve tissues such as the brain and spinal cord. It may perform a fundamental role in the brain.


Pssm-ID: 176569 [Multi-domain]  Cd Length: 253  Bit Score: 202.18  E-value: 8.07e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08632    2 QDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETINK 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNET-CLPSPYAMRRKILLKHKKL 239
Cdd:cd08632   82 YAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTGDPkQLPSPQLLKGKILVKGKKL 149
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 93-239 2.02e-56

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 4. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta4 is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176563 [Multi-domain]  Cd Length: 257  Bit Score: 195.75  E-value: 2.02e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGP--DGMPFIFHGHTLTTKIKFLDVIKTI 170
Cdd:cd08626    2 QDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQAI 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 307167498 171 KEHAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNET----CLPSPYAMRRKILLKHKKL 239
Cdd:cd08626   82 KDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLESHPLepgvPLPSPNKLKRKILIKNKRL 154
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 93-238 7.24e-56

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family corresponds to the catalytic domain presenting in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-zeta isozyme. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-zeta represents a class of sperm-specific PI-PLC that has an N-terminal EF-hand domain, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PLC-zeta isozyme (1). PLC-zeta plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176537 [Multi-domain]  Cd Length: 257  Bit Score: 194.00  E-value: 7.24e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08595    2 QDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVEK 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETC-LPSPYAMRRKILLKHKK 238
Cdd:cd08595   82 YAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPATGeLPSPEALKFKILVKNKK 148
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 711-826 8.84e-55

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 128454 [Multi-domain]  Cd Length: 115  Bit Score: 185.52  E-value: 8.84e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   711 SNLIVYCRSVAFNIERIRTKGFTFNEMSSFPETKAEKLMcQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGC 790
Cdd:smart00149   1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLL-KKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGC 79

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 307167498   791 QMVALNYQTGDKSMQLNQAKFKENGNCGYLLKPEFM 826
Cdd:smart00149  80 QMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 845-968 1.39e-52

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 179.66  E-value: 1.39e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 845 LKICLKVIGARHLMKSG---RGTASPSIEVEIIGADFDSGTKLTTKTIPDNGFNPMWNETCEFEIFNPYFALIRFLVQDE 921
Cdd:cd00275    2 LTLTIKIISGQQLPKPKgdkGSIVDPYVEVEIHGLPADDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDE 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 307167498 922 DMFGDsNFIGQATYPVRCLRTGYRSVPLKNVYSEDLELASLLVHIKI 968
Cdd:cd00275   82 DSGDD-DFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDI 127
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 93-237 9.06e-51

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) encoded by PLC genes from higher plants, which are homologs of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The domain arrangement of plant PI-PLCs is structurally similar to the mammalian PLC-zeta isoform, which lacks the N-terminal pleckstrin homology (PH) domain, but contains EF-hand like motifs (which are absent in a few plant PLCs), a PLC catalytic core domain with X- and Y- highly conserved regions split by a linker sequence, and a C2 domain. However, at the sequence level, the plant PI-PLCs are closely related to the mammalian PLC-delta isoform. Experiments show that plant PLCs display calcium dependent PLC catalytic properties, although they lack some of the N-terminal motifs found in their mammalian counterparts. A putative calcium binding site may be located at the region spanning the X- and Y- domains.


Pssm-ID: 176541 [Multi-domain]  Cd Length: 228  Bit Score: 178.33  E-value: 9.06e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLTTKIKFLDVIKTIKE 172
Cdd:cd08599    2 HDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIKE 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 307167498 173 HAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHK 237
Cdd:cd08599   82 NAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPDSEDLPEEFPSPEELKGKILISDK 146
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 327-425 3.83e-50

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 171.77  E-value: 3.83e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 327 HFGEKWFHGKLARGREEAEELLRHYSYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGQTQYYLIDTNCFD 406
Cdd:cd10341    1 HFTEPWFHGKLGDGRDEAEKLLLEYCEGGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQENGEKKYYLTDNLVFD 80

                         90
                 ....*....|....*....
gi 307167498 407 SLYSLITHYRNHPLRSQEF 425
Cdd:cd10341   81 SLYELIDYYRQNPLRCAEF 99
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 92-238 2.12e-49

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta2 is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176561 [Multi-domain]  Cd Length: 261  Bit Score: 176.02  E-value: 2.12e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  92 SQDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDG--PDGMPFIFHGHTLTTKIKFLDVIKT 169
Cdd:cd08624    1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEA 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 307167498 170 IKEHAFATSEYPVILSIEDNCTLP-QQRKMAMSMQEVFGDMLLVQPVDKNE----TCLPSPYAMRRKILLKHKK 238
Cdd:cd08624   81 IAESAFKTSPYPVILSFENHVDSPkQQAKMAEYCRTIFGDMLLTEPLEKYPlkpgVPLPSPEDLRGKILIKNKK 154
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 92-239 1.27e-46

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 3. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta3 is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176562 [Multi-domain]  Cd Length: 258  Bit Score: 167.92  E-value: 1.27e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  92 SQDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDG--PDGMPFIFHGHTLTTKIKFLDVIKT 169
Cdd:cd08625    1 SDDMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEA 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 307167498 170 IKEHAFATSEYPVILSIEDNC-TLPQQRKMAMSMQEVFGDMLLVQPVDKNE----TCLPSPYAMRRKILLKHKKL 239
Cdd:cd08625   81 IAESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPlvpgVQLPSPQELMGKILVKNKKM 155
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 734-814 2.94e-46

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily.


Pssm-ID: 176534 [Multi-domain]  Cd Length: 229  Bit Score: 165.68  E-value: 2.94e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 734 FNEMSSFPETKAEKLMCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKE 813
Cdd:cd08592  149 FYEMSSFPETKAEKYLNRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFML 228


                 .
gi 307167498 814 N 814
Cdd:cd08592  229 N 229
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 705-814 1.18e-41

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. Aside from three PI-PLC-delta isozymes identified in mammals, some eukaryotic PI-PLC-delta homologs have been classified to this CD.


Pssm-ID: 176535 [Multi-domain]  Cd Length: 257  Bit Score: 153.26  E-value: 1.18e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 705 RIAKEMSNLIVYCRSVAF-NIERIRTKGfTFNEMSSFPETKAEKLMCQQENKFfIKYHQIQFSRVYPKGQRIDSSNYNPV 783
Cdd:cd08593  149 KLAKELSDLVIYCKSVHFkSFEHSKENY-HFYEMSSFSESKALKLAQESGNEF-VRHNKRQLSRIYPAGLRTDSSNYDPQ 226

                         90       100       110
                 ....*....|....*....|....*....|.
gi 307167498 784 PMWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08593  227 EMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 735-814 6.81e-41

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; This family corresponds to the catalytic domain present in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) and similar proteins. The higher eukaryotic PI-PLCs play a critical role in most signal transduction pathways, controlling numerous cellular events such as cell growth, proliferation, excitation and secretion. They strictly require Ca2+ for the catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated membrane phospholipids PI-analogues, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP), to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. The eukaryotic PI-PLCs have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains, such as the pleckstrin homology (PH) domain, EF-hand motif, and C2 domain. The catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a linker region. The catalytic mechanism of eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. The mammalian PI-PLCs consist of 13 isozymes, which are classified into six-subfamilies, PI-PLC-delta (1,3 and 4), -beta(1-4), -gamma(1,2), -epsilon, -zeta, and -eta (1,2). Ca2+ is required for the activation of all forms of mammalian PI-PLCs, and the concentration of calcium influences substrate specificity. This family also includes metazoan phospholipase C related but catalytically inactive proteins (PRIP), which belong to a group of novel inositol trisphosphate binding proteins. Due to the replacement of critical catalytic residues, PRIP does not have PLC enzymatic activity.


Pssm-ID: 176501 [Multi-domain]  Cd Length: 226  Bit Score: 150.29  E-value: 6.81e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 735 NEMSSFPETKAEKLmCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08558  148 YHMSSFSETKALKL-LKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 92-243 5.89e-40

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta1 is expressed at highest levels in specific regions of the brain. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176560 [Multi-domain]  Cd Length: 258  Bit Score: 148.69  E-value: 5.89e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  92 SQDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDG--PDGMPFIFHGHTLTTKIKFLDVIKT 169
Cdd:cd08623    1 NEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEA 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 307167498 170 IKEHAFATSEYPVILSIEDNCTLP-QQRKMAMSMQEVFGDMLLVQPVDK----NETCLPSPYAMRRKILLKHKKLPDGV 243
Cdd:cd08623   81 IAECAFKTSPFPILLSFENHVDSPkQQAKMAEYCRLIFGDALLMEPLEKypleSGVPLPSPMDLMYKILVKNKKMSNLV 159
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 93-239 1.49e-39

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This subfamily corresponds to the catalytic domain present in prokaryotic and eukaryotic phosphoinositide-specific phospholipase C (PI-PLC), which is a ubiquitous enzyme catalyzing the cleavage of the sn3-phosphodiester bond in the membrane phosphoinositides (phosphatidylinositol, PI; Phosphatidylinositol-4-phosphate, PIP; phosphatidylinositol 4,5-bisphosphate, PIP2) to yield inositol phosphates (inositol monosphosphate, InsP; inositol diphosphate, InsP2; inositol trisphosphate, InsP3) and diacylglycerol (DAG). The higher eukaryotic PI-PLCs (EC 3.1.4.11) have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. They play a critical role in most signal transduction pathways, controlling numerous cellular events, such as cell growth, proliferation, excitation and secretion. These PI-PLCs strictly require Ca2+ for their catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated PI-analogues, PIP2 and PIP, to generate two important second messengers, InsP3 and DAG. InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. In contrast, bacterial PI-PLCs contain a single catalytic domain. Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. They participate in Ca2+-independent PI metabolism. They are characterized as phosphatidylinositol-specific phospholipase C (EC 4.6.1.13) that selectively hydrolyze PI, not PIP or PIP2. The TIM-barrel type catalytic domain in bacterial PI-PLCs is very similar to the one in eukaryotic PI-PLCs, in which the catalytic domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. The catalytic mechanism of both prokaryotic and eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host#s immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.


Pssm-ID: 176497 [Multi-domain]  Cd Length: 274  Bit Score: 148.18  E-value: 1.49e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  93 QDMARPLAHYWIASSHNTYLMGDQISSE-----SSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLtTKIKFLDVI 167
Cdd:cd00137    2 HPDTQPLAHYSIPGTHDTYLTAGQFTIKqvwglTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTF-LDIFLKEVI 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 307167498 168 KTIKEHAFATSEYPVILSIEDNCTLP--QQRKMAMSMQEVFGDMLLVQPVDKNETcLPSPYAMRRKILLKHKKL 239
Cdd:cd00137   81 EAIAQFLKKNPPETIIMSLKNEVDSMdsFQAKMAEYCRTIFGDMLLTPPLKPTVP-LPSLEDLRGKILLLNKKN 153
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 705-814 2.25e-35

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta1 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This subfamily corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1and 3 from the cell nucleus. Experiments show PI-PLC-delta1 is essential for normal hair formation.


Pssm-ID: 176566 [Multi-domain]  Cd Length: 258  Bit Score: 135.55  E-value: 2.25e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 705 RIAKEMSNLIVYCRSVAFN-IERIRTKGFTFNEMSSFPETKAEKLmCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPV 783
Cdd:cd08629  149 KLVPELSDMIIYCKSVHFGgFSSPGTSGQAFYEMASFSESRALRL-LQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPV 227

                         90       100       110
                 ....*....|....*....|....*....|.
gi 307167498 784 PMWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08629  228 EMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 708-814 6.30e-35

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PLC-beta isozymes (1-4). They are activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. The beta-gamma subunits of heterotrimeric G proteins are known to activate the PLC-beta2 and -beta3 isozymes only. Aside from four PLC-beta isozymes identified in mammals, some eukaryotic PLC-beta homologs have been classified into this subfamily, such as NorpA and PLC-21 from Drosophila and PLC-beta from turkey, Xenopus, sponge, and hydra.


Pssm-ID: 176533 [Multi-domain]  Cd Length: 257  Bit Score: 134.00  E-value: 6.30e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 708 KEMSNLIVYCRSVAFNIERIRTKGFTFNEMSSFPETKAEKLMCQQENKFfIKYHQIQFSRVYPKGQRIDSSNYNPVPMWN 787
Cdd:cd08591  152 KKLSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEF-VNYNKRQLSRIYPKGTRVDSSNYMPQIFWN 230

                         90       100
                 ....*....|....*....|....*..
gi 307167498 788 AGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08591  231 AGCQMVALNFQTPDLPMQLNQGKFEYN 257
PLN02952 PLN02952
phosphoinositide phospholipase C
 739-964 9.15e-34

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 138.21  E-value: 9.15e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 739 SFPETKAEKlMCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKENGNCG 818
Cdd:PLN02952 364 SLSEQELEK-AATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCG 442

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 819 YLLKPEFMFRQDFNP--YD-KNTLYGVESLKIclKVI---GAR-HLMKSGRGTASPS---IEVEIIGADFDSGTKlTTKT 888
Cdd:PLN02952 443 YLKKPDFLMKKGFHDevFDpKKKLPVKKTLKV--KVYlgdGWRlDFSHTHFDSYSPPdfyTKMYIVGVPADNAKK-KTKI 519

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 307167498 889 IPDNgFNPMWNETCEFEIFNPYFALIRFLVQDEDMFGDSNFIGQATYPVRCLRTGYRSVPLKNVYSEDLELASLLV 964
Cdd:PLN02952 520 IEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLM 594
PLN02952 PLN02952
phosphoinositide phospholipase C
 23-237 1.50e-33

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 137.44  E-value: 1.50e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  23 VTLQEFQNFLLtEQQDSLGNNELEISRFIREYLQdpQRDIQEPY----FTFSEFVDFLFskQNDIWNQKFNQVSQDMARP 98
Cdd:PLN02952  54 MGADQLRRFLV-LHQDELDCTLAEAQRIVEEVIN--RRHHVTRYtrhgLNLDDFFHFLL--YDDLNGPITPQVHHDMTAP 128

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  99 LAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMP-FIFHGHTLTTKIKFLDVIKTIKEHAFAT 177
Cdd:PLN02952 129 LSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEiLVLHGRTLTTPVPLIKCLKSIRDYAFSS 208

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 178 SEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVqPVDKNETCLPSPYAMRRKILLKHK 237
Cdd:PLN02952 209 SPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYY-PESDSLVQFPSPESLKHRIIISTK 267
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 72-237 8.13e-33

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 135.16  E-value: 8.13e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  72 FVDFLFSKQNDiwNQKFNQVSQDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCW-----DGPD 146
Cdd:PLN02222  84 FFKYLFGDNNP--PLALHEVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWpnsdkDDID 161

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 147 gmpfIFHGHTLTTKIKFLDVIKTIKEHAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPY 226
Cdd:PLN02222 162 ----VLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFTPPVGESLKEFPSPN 237

                        170
                 ....*....|.
gi 307167498 227 AMRRKILLKHK 237
Cdd:PLN02222 238 SLKKRIIISTK 248
PLN02228 PLN02228
Phosphoinositide phospholipase C
 72-237 1.40e-32

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 134.39  E-value: 1.40e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  72 FVDFLFSKQNDIWNQKfNQVSQDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPF- 150
Cdd:PLN02228  86 FYRYLFSDTNSPLPMS-GQVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGNAAe 164

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 151 IFHGHTLTTKIKFLDVIKTIKEHAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLvQPVDKNETCLPSPYAMRR 230
Cdd:PLN02228 165 VRHGRTLTSHEDLQKCLNAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLF-RCTSESTKHFPSPEELKN 243


                 ....*..
gi 307167498 231 KILLKHK 237
Cdd:PLN02228 244 KILISTK 250
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 734-814 2.46e-32

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma1, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma1 is ubiquitously expressed. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region.


Pssm-ID: 176564 [Multi-domain]  Cd Length: 229  Bit Score: 125.53  E-value: 2.46e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 734 FNEMSSFPETKAEKLMCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKE 813
Cdd:cd08627  149 YRDMSSFPETKAEKYVNRSKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFML 228


                 .
gi 307167498 814 N 814
Cdd:cd08627  229 G 229
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 705-814 9.60e-32

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta4 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4. Experiments show PI-PLC-delta4 is required for the acrosome reaction in fertilization.


Pssm-ID: 176568 [Multi-domain]  Cd Length: 258  Bit Score: 125.06  E-value: 9.60e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 705 RIAKEMSNLIVYCRSVAFNIERIRTKGFTFNEMSSFPETKAEKLMCQQENKFfIKYHQIQFSRVYPKGQRIDSSNYNPVP 784
Cdd:cd08631  150 RLSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREAGNEF-VQHNTWQLSRVYPSGLRTDSSNYNPQE 228

                         90       100       110
                 ....*....|....*....|....*....|
gi 307167498 785 MWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08631  229 MWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 696-814 1.38e-31

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 2. PI-PLC is a signaling enzyme that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma2, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma2 is highly expressed in cells of hematopoietic origin. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.


Pssm-ID: 176565 [Multi-domain]  Cd Length: 254  Bit Score: 124.40  E-value: 1.38e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 696 QHKEMerawrIAKEMSNLIVYCRSVAfnIERIRTKGFTFNEMSSFPETKAEKLMCQQENKFfIKYHQIQFSRVYPKGQRI 775
Cdd:cd08628  144 KHKKL-----IAIELSDLVVYCKPTS--KTKDNLENPDFKEIRSFVETKAPSIIRQKPVQL-LKYNRKGLTRVYPKGQRV 215

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 307167498 776 DSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08628  216 DSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFSLN 254
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 739-969 2.95e-31

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 130.15  E-value: 2.95e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 739 SFPETKAEKlMCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKENGNCG 818
Cdd:PLN02222 346 SLSEEQLEK-AAEKYAKQIVRFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCG 424

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 819 YLLKPEFMFRQD-----FNPydKNTLYGVESLKICLKV-----IGARHLMKSGRGTASPSIEVEIIGADFDSGTKlTTKT 888
Cdd:PLN02222 425 YIKKPDLLLKSGsdsdiFDP--KATLPVKTTLRVTIYMgegwyFDFRHTHFDQYSPPDFYTRVGIAGVPGDTVMK-KTKT 501

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 889 IPDNgFNPMWNETCEFEIFNPYFALIRFLVQDEDMFGDSNFIGQATYPVRCLRTGYRSVPLKNVYSEDLELASLLVHIKI 968
Cdd:PLN02222 502 LEDN-WIPAWDEVFEFPLTVPELALLRLEVHEYDMSEKDDFGGQTCLPVWELSQGIRAFPLHSRKGEKYKSVKLLVKVEF 580


                 .
gi 307167498 969 I 969
Cdd:PLN02222 581 V 581
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 684-814 5.86e-31

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta1 is a neuron-specific enzyme and expressed in only nerve tissues such as the brain and spinal cord. It may perform a fundamental role in the brain.


Pssm-ID: 176569 [Multi-domain]  Cd Length: 253  Bit Score: 122.45  E-value: 5.86e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 684 KETAQNASVRESQHKEMERAWRIAKEMSNLIVYCRSVAfnIERIRTKGFTFNEMSsFPETKAEKLMcQQENKFFIKYHQI 763
Cdd:cd08632  127 GDPKQLPSPQLLKGKILVKGKKLCRDLSDLVVYTNSVA--AQDIVDDGSTGNVLS-FSETRAHQLV-QQKAEQFMTYNQK 202

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 307167498 764 QFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08632  203 QLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
 1-80 3.80e-30

EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); PI-PLC-gamma isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. They can form a complex with the phosphorylated cytoplasmic domains of the immunoglobulin Ig-alpha and Ig-beta subunits of the B cell receptor (BCR), the membrane-tethered Src family kinase Lyn, phosphorylated spleen tyrosine kinase (Syk), the phosphorylated adaptor protein B-cell linker (BLNK), and activated Bruton's tyrosine kinase (Btk). Like other PI-PLC isozymes, PI-PLC-gamma isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker. The SH2 and SH3 domains are responsible for the binding of phosphotyrosine-containing sequences and proline-rich sequences, respectively. There are two PI-PLC-gamma isozymes (1-2), both of which are activated by receptor and non-receptor tyrosine kinases due to the presence of SH2 and SH3 domains.


Pssm-ID: 320031 [Multi-domain]  Cd Length: 145  Bit Score: 116.52  E-value: 3.80e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   1 MFDQNNLADWHKLLNYSQIEPTVTLQEFQNFLLTEQQDSLGNNELEISRFIREYLQDPQRDIQEPYFTFSEFVDFLFSKQ 80
Cdd:cd16201   66 MFDQKIIEDFFKKYSYSSDGQTVTLEDFQRFLLEEQKEPWANDPNAVREFMRDFLQDPLRDVQEPYFTLDEFLDYLFSKE 145
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 1-310 9.05e-30

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 125.97  E-value: 9.05e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   1 MFDQNNLADWHKLL-NYSQIEPTVTLQEFQNfLLTEQQDSLGNNELE-ISRFIREYLQDPQR--DIQEPYFTFSEFVDFL 76
Cdd:PLN02230  22 MTESGPVADVRDLFeKYADGDAHMSPEQLQK-LMAEEGGGEGETSLEeAERIVDEVLRRKHHiaKFTRRNLTLDDFNYYL 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  77 FSkqNDIWNQKFNQVSQDMARPLAHYWIASSHNTYLMGDQISSESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHT 156
Cdd:PLN02230 101 FS--TDLNPPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRGTDDVCVKHGRT 178

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 157 LTTKIKFLDVIKTIKEHAFATSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQpvdKNETC--LPSPYAMRRKILL 234
Cdd:PLN02230 179 LTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYH---DSEGCqeFPSPEELKEKILI 255

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 307167498 235 KHKKlpdgvdESSFLVRNDESRqemdlRNTVKNGILYLEDPIDKEwnPHFFVLTQQKLfyTDTFSRVQETEHDDDE 310
Cdd:PLN02230 256 STKP------PKEYLEANDAKE-----KDNGEKGKDSDEDVWGKE--PEDLISTQSDL--DKVTSSVNDLNQDDEE 316
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 705-814 2.06e-29

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta2 is a neuron-specific enzyme and expressed in the brain. It may in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain.


Pssm-ID: 176570 [Multi-domain]  Cd Length: 254  Bit Score: 118.22  E-value: 2.06e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 705 RIAKEMSNLIVYCRSVAfnIERIRTKGFTFNEMSSFPETKAEKLMcQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVP 784
Cdd:cd08633  148 KLSRALSDLVKYTKSVR--VHDIETEATSSWQVSSFSETKAHQIL-QQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQP 224

                         90       100       110
                 ....*....|....*....|....*....|
gi 307167498 785 MWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08633  225 FWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 736-814 9.79e-28

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are two PI-PLC-eta isozymes (1-2), both neuron-specific enzymes. They function as calcium sensors that are activated by small increases in intracellular calcium concentrations. The PI-PLC-eta isozymes are also activated through GPCR stimulation. Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 176536 [Multi-domain]  Cd Length: 227  Bit Score: 112.20  E-value: 9.79e-28
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 307167498 736 EMSSFPETKAEKLMcQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08594  150 QVSSFSETRAHQIV-QQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 708-814 1.00e-27

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 4. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta4 is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176563 [Multi-domain]  Cd Length: 257  Bit Score: 113.32  E-value: 1.00e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 708 KEMSNLIVYCRSVAF-NIERIRTKGFTFNeMSSFPETKAEKLmCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMW 786
Cdd:cd08626  152 KRLSSLVNYAQPVKFqGFDVAEERNIHFN-MSSFNESVGLGY-LKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFW 229

                         90       100
                 ....*....|....*....|....*...
gi 307167498 787 NAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08626  230 NAGCQMVSLNFQTPDLGMQLNQGKFEYN 257
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 708-814 1.38e-27

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta2 is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176561 [Multi-domain]  Cd Length: 261  Bit Score: 112.84  E-value: 1.38e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 708 KEMSNLIVYCRS---VAFNIERIRTKGFTfneMSSFPETKAEKLMCQQENKFfIKYHQIQFSRVYPKGQRIDSSNYNPVP 784
Cdd:cd08624  156 EEMSSLVNYIQPtkfVSFEFSAQKNRSYV---ISSFTELKAYDLLSKASVQF-VEYNKRQMSRIYPKGTRMDSSNYMPQM 231

                         90       100       110
                 ....*....|....*....|....*....|
gi 307167498 785 MWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08624  232 FWNVGCQMVALNFQTMDLPMQQNMALFEFN 261
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 708-814 1.94e-27

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta1 is expressed at highest levels in specific regions of the brain. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension.


Pssm-ID: 176560 [Multi-domain]  Cd Length: 258  Bit Score: 112.48  E-value: 1.94e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 708 KEMSNLIVYCRSVAFNIERIRTKGFTFNEMSSFPETKAEKLMCQQENKFfIKYHQIQFSRVYPKGQRIDSSNYNPVPMWN 787
Cdd:cd08623  153 KKMSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKGLEQLTKSPVEF-VEYNKMQLSRIYPKGTRVDSSNYMPQLFWN 231

                         90       100
                 ....*....|....*....|....*..
gi 307167498 788 AGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08623  232 AGCQMVALNFQTVDLSMQINMGMYEYN 258
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 708-814 2.31e-27

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 3. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta3 is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins.


Pssm-ID: 176562 [Multi-domain]  Cd Length: 258  Bit Score: 112.07  E-value: 2.31e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 708 KEMSNLIVYCRSVAFNIERIRTKGFTFNEMSSFPETKAEKLMCQQENKFfIKYHQIQFSRVYPKGQRIDSSNYNPVPMWN 787
Cdd:cd08625  153 KKMSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSPMEF-VEYNKKQLSRIYPKGTRVDSSNYMPQLFWN 231

                         90       100
                 ....*....|....*....|....*..
gi 307167498 788 AGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08625  232 VGCQMVALNFQTLDLAMQLNMGVFEYN 258
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 705-814 2.73e-27

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta3 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This family corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus.


Pssm-ID: 176567 [Multi-domain]  Cd Length: 258  Bit Score: 112.04  E-value: 2.73e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 705 RIAKEMSNLIVYCRSVAFNIERIRTKGFTFNEMSSFPETKAEKLMcQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVP 784
Cdd:cd08630  150 QISPELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLI-REAGNSFVRHNARQLTRVYPLGLRMNSANYSPQE 228

                         90       100       110
                 ....*....|....*....|....*....|
gi 307167498 785 MWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08630  229 MWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 706-814 2.76e-27

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This family corresponds to the catalytic domain present in metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel Inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(previously known as p130 or PLC-1), which is predominantly expressed in the brain, and PRIP-2 (previously known as PLC-2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses.


Pssm-ID: 176539 [Multi-domain]  Cd Length: 260  Bit Score: 112.13  E-value: 2.76e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 706 IAKEMSNLIVYCRSVAFNIERIRTKGFTFNEMSSFPETKAEKLmCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPM 785
Cdd:cd08597  153 LCKELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRL-ANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDF 231

                         90       100
                 ....*....|....*....|....*....
gi 307167498 786 WNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08597  232 WNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 733-811 2.80e-25

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this CD is protein Plc1p encoded by PLC1 genes from Saccharomyces cerevisiae. Plc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that Plc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like Plc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 176540 [Multi-domain]  Cd Length: 231  Bit Score: 105.41  E-value: 2.80e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 733 TFNEMSSFPETKAEKLMcqQENKFFIKYHQIQF-SRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKF 811
Cdd:cd08598  151 TPNHIFSLSERSLLKLL--KDKRAALDKHNRRHlMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMF 228
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 705-814 1.03e-24

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family corresponds to the catalytic domain presenting in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-zeta isozyme. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-zeta represents a class of sperm-specific PI-PLC that has an N-terminal EF-hand domain, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PLC-zeta isozyme (1). PLC-zeta plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176537 [Multi-domain]  Cd Length: 257  Bit Score: 104.63  E-value: 1.03e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 705 RIAKEMSNLIVYCRSVAFnierirtKGFT-------FNEMSSFPETKAEKLMCQQENKFFikYHQIQF-SRVYPKGQRID 776
Cdd:cd08595  149 KIAKALSDLVIYTKSEKF-------CSFThsrdnqhSYENNSIGENKARKLLKSSGADFV--GHTQRFiTRIYPKGTRAS 219

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 307167498 777 SSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08595  220 SSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 758-951 3.06e-24

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 108.64  E-value: 3.06e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 758 IKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKENGNCGYLLKPEFMFR-----QDFN 832
Cdd:PLN02230 381 IRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDFLMDagpngQDFY 460

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 833 PYDKNTLYGVESLKICLKVIGARHLMKSGRGTASPS---IEVEIIGADFDSGTKLTtkTIPDNGFNPMWNETCEFEIFNP 909
Cdd:PLN02230 461 PKDNSCPKKTLKVKVCMGDGWLLDFKKTHFDSYSPPdffVRVGIAGAPVDEVMEKT--KIEYDTWTPIWNKEFIFPLAVP 538

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 307167498 910 YFALIRFLVQDEDMFGDSNFIGQATYPVRCLRTGYRSVPLKN 951
Cdd:PLN02230 539 ELALLRVEVHEHDINEKDDFGGQTCLPVSEIRQGIHAVPLFN 580
PLN02228 PLN02228
Phosphoinositide phospholipase C
 757-964 5.75e-24

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 107.43  E-value: 5.75e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 757 FIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKENGNCGYLLKPEFMFRQD--FNPY 834
Cdd:PLN02228 345 LVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEHtlFDPC 424

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 835 DKntlygvESLKICLKVigarhLMKSGRG-----------TASPS---IEVEIIGADFDSGTkLTTKTIPDNGFnPMW-N 899
Cdd:PLN02228 425 KR------LPIKTTLKV-----KIYTGEGwdldfhlthfdQYSPPdffVKIGIAGVPRDTVS-YRTETAVDQWF-PIWgN 491

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 307167498 900 ETCEFEIFNPYFALIRFLVQDEDMFGDSNFIGQATYPVRCLRTGYRSVPLKNVYSEDLELASLLV 964
Cdd:PLN02228 492 DEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRAVRLHDRAGKAYKNTRLLV 556
SH3_PLCgamma cd11825
Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of ...
 562-610 7.12e-24

Src homology 3 domain of Phospholipase C (PLC) gamma; PLC catalyzes the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG) in response to various receptors. Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma catalyzes this reaction in tyrosine kinase-dependent signaling pathways. It is activated and recruited to its substrate at the membrane. Vertebrates contain two forms of PLCgamma, PLCgamma1, which is widely expressed, and PLCgamma2, which is primarily found in haematopoietic cells. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212759 [Multi-domain]  Cd Length: 54  Bit Score: 95.09  E-value: 7.12e-24
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYVEE 610
Cdd:cd11825    6 YDYRAQRPDELSFCKHAIITNVEKEDGGWWRGDYGGKKQKWFPANYVEE 54
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 330-421 1.70e-23

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 94.99  E-value: 1.70e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   330 EKWFHGKLarGREEAEELLRHYsylGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKlKQEMGqtQYYLIDTNCFDSLY 409
Cdd:smart00252   1 QPWYHGFI--SREEAEKLLKNE---GDGDFLVRDSESSPGDYVLSVRVKGKVKHYRIR-RNEDG--KFYLEGGRKFPSLV 72

                           90
                   ....*....|..
gi 307167498   410 SLITHYRNHPLR 421
Cdd:smart00252  73 ELVEHYQKNSLG 84
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 707-814 1.79e-23

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-epsilon isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-epsilon represents a class of mammalian PI-PLC that has an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and two predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PI-PLC-epsilon isozyme (1). PI-PLC-epsilon is activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Aside from PI-PLC-epsilon identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176538 [Multi-domain]  Cd Length: 254  Bit Score: 100.69  E-value: 1.79e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 707 AKEMSNLIVYCRSVAFnierirtKGF---TFNEMSSFPETKAEKLMCQQENKFfIKYHQIQFSRVYPKGQRIDSSNYNPV 783
Cdd:cd08596  152 APELSDLVIYCQAVKF-------PGLstpKCYHISSLNENAAKRLCRRYPQKL-VQHTRCQLLRTYPAATRIDSSNPNPL 223

                         90       100       110
                 ....*....|....*....|....*....|.
gi 307167498 784 PMWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08596  224 IFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254
SH3_PLCgamma1 cd11970
Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is ...
 562-611 4.85e-23

Src homology 3 domain of Phospholipase C (PLC) gamma 1; PLCgamma1 is widely expressed and is essential in growth and development. It is activated by the TrkA receptor tyrosine kinase and functions as a key regulator of cell differentiation. It is also the predominant PLCgamma in T cells and is required for T cell and NK cell function. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. The SH3 domain of PLCgamma1 directly interacts with dynamin-1 and can serve as a guanine nucleotide exchange factor (GEF). It also interacts with Cbl, inhibiting its phosphorylation and activity. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212903  Cd Length: 60  Bit Score: 93.13  E-value: 4.85e-23
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYVEEI 611
Cdd:cd11970   10 FDYKAQREDELTFTKNAIIQNVEKQEGGWWRGDYGGKKQLWFPSNYVEEI 59
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 443-524 9.08e-23

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 93.06  E-value: 9.08e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   443 EWWHPECTRIAAEEMLKRIPtDGAFLVRPSERESNCYAISFRAEKKIKHCKIKL--EGRLYTTGTVQFESLVELINYYER 520
Cdd:smart00252   2 PWYHGFISREEAEKLLKNEG-DGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRneDGKFYLEGGRKFPSLVELVEHYQK 80


                   ....
gi 307167498   521 RPLY 524
Cdd:smart00252  81 NSLG 84
SH2 pfam00017
SH2 domain;
332-415 2.46e-22

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 91.51  E-value: 2.46e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  332 WFHGKLarGREEAEELLRhySYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIklkQEMGQTQYYLIDTNCFDSLYSL 411
Cdd:pfam00017   1 WYHGKI--SRQEAERLLL--NGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKI---QSTDNGGYYISGGVKFSSLAEL 73


                  ....
gi 307167498  412 ITHY 415
Cdd:pfam00017  74 VEHY 77
SH2 pfam00017
SH2 domain;
444-518 1.22e-21

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 89.58  E-value: 1.22e-21
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498  444 WWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIK--LEGRLYTTGTVQFESLVELINYY 518
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQstDNGGYYISGGVKFSSLAELVEHY 77
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 443-518 4.08e-19

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 82.50  E-value: 4.08e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 443 EWWHPECTRIAAEEMLKRiPTDGAFLVRPSERESNCYAISFRAE-KKIKHCKIKLEGRLYTTG---TVQFESLVELINYY 518
Cdd:cd00173    1 PWFHGSISREEAERLLRG-KPDGTFLVRESSSEPGDYVLSVRSGdGKVKHYLIERNEGGYYLLggsGRTFPSLPELVEHY 79
PLN02223 PLN02223
phosphoinositide phospholipase C
 758-949 4.39e-19

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 92.01  E-value: 4.39e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 758 IKYHQIQFSRVYPKGQRIDS-SNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKENGNCGYLLKPEFMFrqdfNPYDK 836
Cdd:PLN02223 321 ISFTQKKFLRTRPKKKNLLInAPYKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLL----NAGPS 396

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 837 NTLYGVESlKICLKVIGARHLM----------KSGRgTASPSIEVEIIGADFDSGTKLTTKTIPDNGFNPMWNETCEFEI 906
Cdd:PLN02223 397 GVFYPTEN-PVVVKILKVKIYMgdgwivdfkkRIGR-LSKPDLYVRISIAGVPHDEKIMKTTVKNNEWKPTWGEEFTFPL 474

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 307167498 907 FNPYFALIRFLVQDEDMFGDSNFIGQATYPVRCLRTGYRSVPL 949
Cdd:PLN02223 475 TYPDLALISFEVYDYEVSTADAFCGQTCLPVSELIEGIRAVPL 517
PLN02223 PLN02223
phosphoinositide phospholipase C
 24-280 1.49e-18

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 90.47  E-value: 1.49e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  24 TLQEFQNFLLTEQ-QDSLGNNELE-ISRFIREYLQDPQRDIQEPYFTFSEFVDFLFSKQND--IWNQKFNQvsqDMARPL 99
Cdd:PLN02223  36 LLPRFIELLDTEKdEDGAGLNAAEkIAAELKRRKCDILAFRNLRCLELDHLNEFLFSTELNppIGDQVRHH---DMHAPL 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 100 AHYWIASSHNTYLMGDQISSES-SCQAYVRALRAGCRCIELDCW-DGPDGMpFIFHGHTLTTKIKFLDVIKTIKEHAFA- 176
Cdd:PLN02223 113 SHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLLpDGKDGI-CVRPKWNFEKPLELQECLDAIKEHAFTk 191

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 177 TSEYPVILSIEDNCTLPQQRKMAMSMQEVFGDMLLVQPVDKNETCLPSPYAMRRKILLKHKKlpdgvdESSFLVRNDEsr 256
Cdd:PLN02223 192 CRSYPLIITFKDGLKPDLQSKATQMIDQTFGDMVYHEDPQHSLEEFPSPAELQNKILISRRP------PKELLYAKAD-- 263

                        250       260
                 ....*....|....*....|....
gi 307167498 257 qemDLRNTVKNGILYLEDPIDKEW 280
Cdd:PLN02223 264 ---DGGVGVRNELEIQEGPADKNY 284
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 846-949 2.87e-18

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 80.99  E-value: 2.87e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498   846 KICLKVIGARHLM-KSGRGTASPSIEVEIIGADfdsGTKLTTKTIPDNGfNPMWNETCEFEIFNPYFALIRFLVQDEDMF 924
Cdd:smart00239   1 TLTVKIISARNLPpKDKGGKSDPYVKVSLDGDP---KEKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*
gi 307167498   925 GDSNFIGQATYPVRCLRTGYRSVPL 949
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
SH3_PLCgamma2 cd11969
Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in ...
 565-611 4.07e-17

Src homology 3 domain of Phospholipase C (PLC) gamma 2; PLCgamma2 is primarily expressed in haematopoietic cells, specifically in B cells. It is activated by tyrosine phosphorylation by B cell receptor (BCR) kinases and is recruited to the plasma membrane where its substrate is located. It is required in pre-BCR signaling and in the maturation of B cells. PLCs catalyze the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] to produce Ins(1,4,5)P3 and diacylglycerol (DAG). Ins(1,4,5)P3 initiates the calcium signaling cascade while DAG functions as an activator of PKC. PLCgamma contains a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, two catalytic regions of PLC domains that flank two tandem SH2 domains, followed by a SH3 domain and C2 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212902  Cd Length: 55  Bit Score: 76.03  E-value: 4.07e-17
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 307167498 565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYVEEI 611
Cdd:cd11969    9 RAKRSDELSFCKGALIHNVSKETGGWWKGDYGGKVQHYFPSNYVEDV 55
C2 pfam00168
C2 domain;
846-945 7.15e-17

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 76.97  E-value: 7.15e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  846 KICLKVIGARHLM-KSGRGTASPSIEVEIIgadfDSGTKLTTKTIpDNGFNPMWNETCEFEIFNPYFALIRFLVQDEDMF 924
Cdd:pfam00168   2 RLTVTVIEAKNLPpKDGNGTSDPYVKVYLL----DGKQKKKTKVV-KNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRF 76

                          90       100
                  ....*....|....*....|.
gi 307167498  925 GDSNFIGQATYPVRCLRTGYR 945
Cdd:pfam00168  77 GRDDFIGEVRIPLSELDSGEG 97
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 332-415 1.06e-16

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 75.57  E-value: 1.06e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLarGREEAEELLRHYSylgDGTFLVRQCVTFVGDYCLSFWRK-GKVNHCRIKLKQemGQTQYYLIDTNCFDSLYS 410
Cdd:cd00173    2 WFHGSI--SREEAERLLRGKP---DGTFLVRESSSEPGDYVLSVRSGdGKVKHYLIERNE--GGYYLLGGSGRTFPSLPE 74


                 ....*
gi 307167498 411 LITHY 415
Cdd:cd00173   75 LVEHY 79
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 736-814 5.40e-16

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) encoded by PLC genes from higher plants, which are homologs of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The domain arrangement of plant PI-PLCs is structurally similar to the mammalian PLC-zeta isoform, which lacks the N-terminal pleckstrin homology (PH) domain, but contains EF-hand like motifs (which are absent in a few plant PLCs), a PLC catalytic core domain with X- and Y- highly conserved regions split by a linker sequence, and a C2 domain. However, at the sequence level, the plant PI-PLCs are closely related to the mammalian PLC-delta isoform. Experiments show that plant PLCs display calcium dependent PLC catalytic properties, although they lack some of the N-terminal motifs found in their mammalian counterparts. A putative calcium binding site may be located at the region spanning the X- and Y- domains.


Pssm-ID: 176541 [Multi-domain]  Cd Length: 228  Bit Score: 78.18  E-value: 5.40e-16
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 307167498 736 EMSSFPETKAEKLMCQQENKFFIKYHQIQFSRVYPKGQRIDSSNYNPVPMWNAGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd08599  150 IRNSLSETQLKKVIEGEHPTDLIEFTQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKFRAN 228
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 106-199 1.03e-15

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases superfamily; The PI-PLC-like phosphodiesterases superfamily represents the catalytic domains of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13), eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11), glycerophosphodiester phosphodiesterases (GP-GDE, EC 3.1.4.46), sphingomyelinases D (SMases D) (sphingomyelin phosphodiesterase D, EC 3.1.4.41) from spider venom, SMases D-like proteins, and phospholipase D (PLD) from several pathogenic bacteria, as well as their uncharacterized homologs found in organisms ranging from bacteria and archaea to metazoans, plants, and fungi. PI-PLCs are ubiquitous enzymes hydrolyzing the membrane lipid phosphoinositides to yield two important second messengers, inositol phosphates and diacylglycerol (DAG). GP-GDEs play essential roles in glycerol metabolism and catalyze the hydrolysis of glycerophosphodiesters to sn-glycerol-3-phosphate (G3P) and the corresponding alcohols that are major sources of carbon and phosphate. Both, PI-PLCs and GP-GDEs, can hydrolyze the 3'-5' phosphodiester bonds in different substrates, and utilize a similar mechanism of general base and acid catalysis with conserved histidine residues, which consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes Neurospora crassa ankyrin repeat protein NUC-2 and its Saccharomyces cerevisiae counterpart, Phosphate system positive regulatory protein PHO81, glycerophosphodiester phosphodiesterase (GP-GDE)-like protein SHV3 and SHV3-like proteins (SVLs). The residues essential for enzyme activities and metal binding are not conserved in these sequence homologs, which might suggest that the function of catalytic domains in these proteins might be distinct from those in typical PLC-like phosphodiesterases.


Pssm-ID: 176498 [Multi-domain]  Cd Length: 179  Bit Score: 75.94  E-value: 1.03e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 106 SSHNTYLMGDQissESSCQAYVRALRAGCRCIELDCWDGPDGMPFIFHGHTLT------TKIKFLDVIKTIKEHAFATSe 179
Cdd:cd08555    2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLKNPD- 77

                         90       100
                 ....*....|....*....|....
gi 307167498 180 YPVILSIEDNC----TLPQQRKMA 199
Cdd:cd08555   78 YTIILSLEIKQdspeYDEFLAKVL 101
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 330-415 2.04e-15

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 72.03  E-value: 2.04e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 330 EKWFHGKLarGREEAEELLRHYSYlGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKlkqEMGQTQYYLI-DTNCFDSL 408
Cdd:cd10347    1 LRWYHGKI--SREVAEALLLREGG-RDGLFLVRESTSAPGDYVLSLLAQGEVLHYQIR---RHGEDAFFSDdGPLIFHGL 74


                 ....*..
gi 307167498 409 YSLITHY 415
Cdd:cd10347   75 DTLIEHY 81
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
 440-523 3.86e-15

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 71.94  E-value: 3.86e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAEEMLKRIPtDGAFLVRPSERESNCYAISFRAEKKIKHCKI--KLEGRLYTTGTVQFESLVELINY 517
Cdd:cd09940    3 SEFLWFVGEMERDTAENRLENRP-DGTYLVRVRPQGETQYALSIKYNGDVKHMKIeqRSDGLYYLSESRHFKSLVELVNY 81


                 ....*.
gi 307167498 518 YERRPL 523
Cdd:cd09940   82 YERNSL 87
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 443-518 4.33e-14

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 68.22  E-value: 4.33e-14
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498 443 EWWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKI-KLEGRLYTTGTVQFESLVELINYY 518
Cdd:cd10354    1 IWFHGKISREEAYNMLVKVGGPGSFLVRESDNTPGDYSLSFRVNEGIKHFKIiPTGNNQFMMGGRYFSSLDDVIDRY 77
EFh_PI-PLCgamma1 cd16214
EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, ...
 20-80 5.95e-14

EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, or PLC-148, or phospholipase C-II (PLC-II), or phospholipase C-gamma-1 (PLC-gamma-1), is abundantly expressed in embryonal cortical structures, neurons, oligodendrocytes and astrocytes, and is involved in various cellular events, including proliferation, differentiation, migration, survival, and cell death. It also associates with many diseases, including epilepsy, Huntington's disease (HD), depression, Alzheimer's disease (AD) and bipolar disorder. PI-PLC-gamma1 plays a critical role in cell migration and tumor cell invasiveness and metastasis. It can mediate the cell motility effects of growth factors, including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF) and hepatocyte growth factor (HGF), as well as adhesion receptors. Moreover, PI-PLC-gamma1 can modulate neurite outgrowth, neuronal cell migration and synaptic plasticity through the Trk receptor. PI-PLC-gamma1 contains an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Besides, PI-PLC-gamma1 has a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region, which are present within this linker. PI-PLC-gamma1 is activated by receptor and non-receptor tyrosine kinases via its two SH2 and a single SH3 domain.


Pssm-ID: 320044  Cd Length: 146  Bit Score: 70.24  E-value: 5.95e-14
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 307167498  20 EPTVTLQEFQNFLLTEQQDSLGNNELEISRFIREYLQDPQRDIQEPYFTFSEFVDFLFSKQ 80
Cdd:cd16214   86 ECKISLEDFQKFLLDYQKELWATDTNQVQEFMFNFLRDPLREIEEPYFSLDEFLTFLFSKE 146
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
 332-417 6.80e-14

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 68.47  E-value: 6.80e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHYsylGDGTFLVRQCVTFVGDY--CLSFwrKGKVNHCRIKL---KQEMGQTQYylidtncFD 406
Cdd:cd09937    5 WFHGKISR--EEAERLLQPP---EDGLFLVRESTNYPGDYtlCVSF--EGKVEHYRVIYrngKLTIDEEEY-------FE 70

                         90
                 ....*....|.
gi 307167498 407 SLYSLITHYRN 417
Cdd:cd09937   71 NLIQLVEHYTK 81
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 722-814 7.64e-14

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This subfamily corresponds to the catalytic domain present in prokaryotic and eukaryotic phosphoinositide-specific phospholipase C (PI-PLC), which is a ubiquitous enzyme catalyzing the cleavage of the sn3-phosphodiester bond in the membrane phosphoinositides (phosphatidylinositol, PI; Phosphatidylinositol-4-phosphate, PIP; phosphatidylinositol 4,5-bisphosphate, PIP2) to yield inositol phosphates (inositol monosphosphate, InsP; inositol diphosphate, InsP2; inositol trisphosphate, InsP3) and diacylglycerol (DAG). The higher eukaryotic PI-PLCs (EC 3.1.4.11) have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. They play a critical role in most signal transduction pathways, controlling numerous cellular events, such as cell growth, proliferation, excitation and secretion. These PI-PLCs strictly require Ca2+ for their catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated PI-analogues, PIP2 and PIP, to generate two important second messengers, InsP3 and DAG. InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. In contrast, bacterial PI-PLCs contain a single catalytic domain. Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. They participate in Ca2+-independent PI metabolism. They are characterized as phosphatidylinositol-specific phospholipase C (EC 4.6.1.13) that selectively hydrolyze PI, not PIP or PIP2. The TIM-barrel type catalytic domain in bacterial PI-PLCs is very similar to the one in eukaryotic PI-PLCs, in which the catalytic domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. The catalytic mechanism of both prokaryotic and eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host#s immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.


Pssm-ID: 176497 [Multi-domain]  Cd Length: 274  Bit Score: 73.07  E-value: 7.64e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 722 FNIERIRTKGFTFNEMSSFPETKA---EKLMCQQENKFFIKYHQIQFSRVYPKGQRI---------DSSNYNPVPMWN-- 787
Cdd:cd00137  167 FVSFEFSTQKNRSYNISSQDEYKAyddEKVKLIKATVQFVDYNKNQLSRNYPSGTSGgtawyyyamDSNNYMPQMFWNan 246

                         90       100
                 ....*....|....*....|....*...
gi 307167498 788 -AGCQMVALNYQTGDKSMQLNQAKFKEN 814
Cdd:cd00137  247 pAGCGIVILDFQTMDLPMQQYMAVIEFN 274
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 442-524 7.90e-14

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198271  Cd Length: 97  Bit Score: 68.13  E-value: 7.90e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 442 KEWWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTTGTVQFESLVELINYYERR 521
Cdd:cd10408    1 NPWYYGKVTRHQAEMALNERGNEGDFLIRDSESSPNDFSVSLKAQGKNKHFKVQLKECVYCIGQRKFSSMEELVEHYKKA 80


                 ...
gi 307167498 522 PLY 524
Cdd:cd10408   81 PIF 83
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
 442-524 1.76e-13

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 67.15  E-value: 1.76e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 442 KEWWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTTGTVQFESLVELINYYERR 521
Cdd:cd09943    1 QPWYYGRITRHQAETLLNEHGHEGDFLIRDSESNPGDYSVSLKAPGRNKHFKVQVVDNVYCIGQRKFHTMDELVEHYKKA 80


                 ...
gi 307167498 522 PLY 524
Cdd:cd09943   81 PIF 83
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 439-523 3.12e-13

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 66.61  E-value: 3.12e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 439 HEEKEWWHPECT--RIAAEEMLK--RIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKL-----EGRLYTTGTVQFE 509
Cdd:cd10341    1 HFTEPWFHGKLGdgRDEAEKLLLeyCEGGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSrqengEKKYYLTDNLVFD 80

                         90
                 ....*....|....
gi 307167498 510 SLVELINYYERRPL 523
Cdd:cd10341   81 SLYELIDYYRQNPL 94
SH2_SH2B_family cd10346
Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein ...
 332-420 3.32e-13

Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein family has 3 members: SH2B1 (SH2-B, PSM), SH2B2 (APS), and SH2B3 (Lnk). SH2B family members contain a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198209  Cd Length: 97  Bit Score: 66.29  E-value: 3.32e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARGreEAEELLRHYSYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLkQEMGQTQyylIDTNCFDSLYSL 411
Cdd:cd10346   10 WFHGTLSRS--DAAQLVLHSGADGHGVFLVRQSETRRGEFVLTFNFQGRAKHLRLTL-NEKGQCR---VQHLWFPSIFDM 83


                 ....*....
gi 307167498 412 ITHYRNHPL 420
Cdd:cd10346   84 LEHFRQNPI 92
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 847-937 7.08e-13

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 65.55  E-value: 7.08e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 847 ICLKVIGARHLMKSGR-GTASPSIEVEiigadFDSGTKLTTKTIPDNgFNPMWNETCEFEIFNPYFALIRFLVQDEDMFG 925
Cdd:cd00030    1 LRVTVIEARNLPAKDLnGKSDPYVKVS-----LGGKQKFKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWDKDRFS 74

                         90
                 ....*....|..
gi 307167498 926 DSNFIGQATYPV 937
Cdd:cd00030   75 KDDFLGEVEIPL 86
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 444-534 2.72e-12

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 63.96  E-value: 2.72e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTT-GTVQFESLVELINYYERRP 522
Cdd:cd10340    2 WFHPVISGIEAENLLKTRGVDGSFLARPSKSNPGDFTLSVRRGDEVTHIKIQNTGDYYDLyGGEKFATLSELVQYYMEQH 81

                         90
                 ....*....|....*...
gi 307167498 523 --LYKK----IKLSHPVN 534
Cdd:cd10340   82 gqLREKngdvIELKYPLN 99
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 442-524 2.88e-12

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198272  Cd Length: 98  Bit Score: 63.90  E-value: 2.88e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 442 KEWWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTTGTVQFESLVELINYYERR 521
Cdd:cd10409    1 KEWYYGNVTRHQAECALNERGVEGDFLIRDSESSPSDFSVSLKAVGKNKHFKVQLVDNVYCIGQRRFNSMDELVEHYKKA 80


                 ...
gi 307167498 522 PLY 524
Cdd:cd10409   81 PIF 83
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 331-415 7.48e-12

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 61.67  E-value: 7.48e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 331 KWFHGKLARgrEEAEELLRHYSylGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIkLKQEMGQtqyYLIDTNCFDSLYS 410
Cdd:cd10354    1 IWFHGKISR--EEAYNMLVKVG--GPGSFLVRESDNTPGDYSLSFRVNEGIKHFKI-IPTGNNQ---FMMGGRYFSSLDD 72


                 ....*
gi 307167498 411 LITHY 415
Cdd:cd10354   73 VIDRY 77
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
 440-520 8.42e-12

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 62.60  E-value: 8.42e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAEEMLK--RIPTdGAFLVRPSERESNCYAISFR-----AEKKIKHCKI-KLE-GRLYTTGTVQFES 510
Cdd:cd09933    1 EAEEWFFGKIKRKDAEKLLLapGNPR-GTFLIRESETTPGAYSLSVRdgddaRGDTVKHYRIrKLDnGGYYITTRATFPT 79

                         90
                 ....*....|
gi 307167498 511 LVELINYYER 520
Cdd:cd09933   80 LQELVQHYSK 89
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
 330-418 1.96e-11

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 61.44  E-value: 1.96e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 330 EKWFHGKLarGREEAEELLRHySYLGDGTFLVRQCVTFVGDYCLS-----FWRKGKVNHCRIKlKQEMGqtqYYLIDTNC 404
Cdd:cd09933    3 EEWFFGKI--KRKDAEKLLLA-PGNPRGTFLIRESETTPGAYSLSvrdgdDARGDTVKHYRIR-KLDNG---GYYITTRA 75

                         90
                 ....*....|....*
gi 307167498 405 -FDSLYSLITHYRNH 418
Cdd:cd09933   76 tFPTLQELVQHYSKD 90
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 439-534 7.80e-11

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 59.73  E-value: 7.80e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 439 HEEKEWWHPECTRIAAEEMLKRIPtDGAFLVRPSeRESNCYAISFRAEKKIKHCKIKLEGRLYttGTVQ----FESLVEL 514
Cdd:cd09930    3 HDERTWLVGDINRTQAEELLRGKP-DGTFLIRES-STQGCYACSVVCNGEVKHCVIYKTETGY--GFAEpynlYESLKEL 78

                         90       100
                 ....*....|....*....|....*
gi 307167498 515 INYYERRPLYK-----KIKLSHPVN 534
Cdd:cd09930   79 VLHYAHNSLEQhndslTVTLAYPVL 103
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
 444-522 9.44e-11

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 59.32  E-value: 9.44e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLkRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIK--LEGRLYTTGTVQFESLVELINYYERR 521
Cdd:cd09935    5 WYHGPISRNAAEYLL-SSGINGSFLVRESESSPGQYSISLRYDGRVYHYRISedSDGKVYVTQEHRFNTLAELVHHHSKN 83


                 .
gi 307167498 522 P 522
Cdd:cd09935   84 A 84
SH3_PIX cd11877
Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine ...
 562-610 1.23e-10

Src Homology 3 domain of Pak Interactive eXchange factors; PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212810 [Multi-domain]  Cd Length: 53  Bit Score: 57.71  E-value: 1.23e-10
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd11877    6 FNFEGTNEDELSFDKGDIITVTQVVEGGWWEGTLNGKTG-WFPSNYVKE 53
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 331-420 1.39e-10

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 58.83  E-value: 1.39e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 331 KWFHGKLARGreEAEELLRhySYLGDGTFLVRQCVTFVGDYCLSFWRK-GKVNHcrIKLKQEMGqtQYYLIDTNCFDSLY 409
Cdd:cd09931    1 RWFHGHLSGK--EAEKLLL--EKGKPGSFLVRESQSKPGDFVLSVRTDdDKVTH--IMIRCQGG--KYDVGGGEEFDSLT 72

                         90
                 ....*....|.
gi 307167498 410 SLITHYRNHPL 420
Cdd:cd09931   73 DLVEHYKKNPM 83
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 444-534 1.43e-10

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 58.83  E-value: 1.43e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRA-EKKIKHCKIKLEGRLYTT-GTVQFESLVELINYYERR 521
Cdd:cd09931    2 WFHGHLSGKEAEKLLLEKGKPGSFLVRESQSKPGDFVLSVRTdDDKVTHIMIRCQGGKYDVgGGEEFDSLTDLVEHYKKN 81

                         90
                 ....*....|....*..
gi 307167498 522 PLYKK----IKLSHPVN 534
Cdd:cd09931   82 PMVETsgtvVHLKQPLN 98
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
 332-420 1.65e-10

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198275  Cd Length: 97  Bit Score: 58.75  E-value: 1.65e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARGReeAEELLRHYSYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLkQEMGQTQYYLIDtncFDSLYSL 411
Cdd:cd10412   10 WFHGPISRVK--AAQLVQLQGPDAHGVFLVRQSETRRGEYVLTFNFQGRAKHLRLSL-TERGQCRVQHLH---FPSVVDM 83


                 ....*....
gi 307167498 412 ITHYRNHPL 420
Cdd:cd10412   84 LHHFQRSPI 92
SH3_Nck1_2 cd11901
Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a ...
 553-610 2.58e-10

Second Src Homology 3 domain of Nck1 adaptor protein; Nck1 (also called Nckalpha) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds and activates RasGAP, resulting in the downregulation of Ras. It is also involved in the signaling of endothilin-mediated inhibition of cell migration. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212834 [Multi-domain]  Cd Length: 55  Bit Score: 56.58  E-value: 2.58e-10
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 553 IPGYMdptSFTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd11901    2 LPAYV---KFNYTAEREDELSLVKGTKVIVMEKCSDGWWRGSYNGQVG-WFPSNYVTE 55
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
 441-523 4.80e-10

Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76); BLNK (also known as SLP-65 or BASH) is an important adaptor protein expressed in B-lineage cells. BLNK consists of a N-terminal sterile alpha motif (SAM) domain and a C-terminal SH2 domain. BLNK is a cytoplasmic protein, but a part of it is bound to the plasma membrane through an N-terminal leucine zipper motif and transiently bound to a cytoplasmic domain of Iga through its C-terminal SH2 domain upon B cell antigen receptor (BCR)-stimulation. A non-ITAM phosphotyrosine in Iga is necessary for the binding with the BLNK SH2 domain and/or for normal BLNK function in signaling and B cell activation. Upon phosphorylation BLNK binds Btk and PLCgamma2 through their SH2 domains and mediates PLCgamma2 activation by Btk. BLNK also binds other signaling molecules such as Vav, Grb2, Syk, and HPK1. BLNK has been shown to be necessary for BCR-mediated Ca2+ mobilization, for the activation of mitogen-activated protein kinases such as ERK, JNK, and p38 in a chicken B cell line DT40, and for activation of transcription factors such as NF-AT and NF-kappaB in human or mouse B cells. BLNK is involved in B cell development, B cell survival, activation, proliferation, and T-independent immune responses. BLNK is structurally homologous to SLP-76. SLP-76 and (linker for activation of T cells) LAT are adaptor/linker proteins in T cell antigen receptor activation and T cell development. BLNK interacts with many downstream signaling proteins that interact directly with both SLP-76 and LAT. New data suggest functional complementation of SLP-76 and LAT in T cell antigen receptor function with BLNK in BCR function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198183  Cd Length: 121  Bit Score: 58.09  E-value: 4.80e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 441 EKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSER--ESNCYAISFRAEKKIKHCKIKL--EGRLYTTGT-----VQFESL 511
Cdd:cd09929   10 PKEWYAGNIDRKEAEEALRRSNKDGTFLVRDSSGkdSSQPYTLMVLYNDKVYNIQIRFleNTRQYALGTglrgeETFSSV 89

                         90
                 ....*....|..
gi 307167498 512 VELINYYERRPL 523
Cdd:cd09929   90 AEIIEHHQKTPL 101
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
 329-436 5.73e-10

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198179  Cd Length: 104  Bit Score: 57.36  E-value: 5.73e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 329 GEKWFHGKLArgREEAEELLRHysylgDGTFLVRQCVTFVGDYCLSFWRKGKVNHcriklkqemgqtqYYLIDTN----- 403
Cdd:cd09925    6 GEPWYHGKMS--RRDAESLLQT-----DGDFLVRESTTTPGQYVLTGMQNGQPKH-------------LLLVDPEgvvrt 65

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 307167498 404 ---CFDSLYSLIT-HYRNH-PLRSQEFLITLQEPVPQP 436
Cdd:cd09925   66 kdrVFESISHLINyHVTNGlPIISEGSELHLRRPVRRP 103
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
 332-433 6.98e-10

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 56.92  E-value: 6.98e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLarGREEAEELLRHYSylgDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGqtqYYLIDTNCFDSLYSL 411
Cdd:cd09940    7 WFVGEM--ERDTAENRLENRP---DGTYLVRVRPQGETQYALSIKYNGDVKHMKIEQRSDGL---YYLSESRHFKSLVEL 78

                         90       100
                 ....*....|....*....|....
gi 307167498 412 ITHYRNHPLR-SQEFL-ITLQEPV 433
Cdd:cd09940   79 VNYYERNSLGeNFAGLdTTLKWPY 102
SH3_Nck_2 cd11766
Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin ...
 562-610 7.18e-10

Second Src Homology 3 domain of Nck adaptor proteins; Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4), which show partly overlapping functions but also bind distinct targets. Their SH3 domains are involved in recruiting downstream effector molecules, such as the N-WASP/Arp2/3 complex, which when activated induces actin polymerization that results in the production of pedestals, or protrusions of the plasma membrane. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212700 [Multi-domain]  Cd Length: 53  Bit Score: 55.35  E-value: 7.18e-10
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd11766    6 FNYEAQREDELSLRKGDRVLVLEKSSDGWWRGECNGQVG-WFPSNYVTE 53
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
 444-523 7.69e-10

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198218  Cd Length: 92  Bit Score: 56.72  E-value: 7.69e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTTGTVQFESLVELINYYERRPL 523
Cdd:cd10355    8 WYHGNLTRHAAEALLLSNGVDGSYLLRNSNEGTGLFSLSVRAKDSVKHFHVEYTGYSFKFGFNEFSSLQDFVKHFANQPL 87
SH3 smart00326
Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences ...
 565-609 8.38e-10

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.


Pssm-ID: 214620 [Multi-domain]  Cd Length: 56  Bit Score: 55.24  E-value: 8.38e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 307167498   565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYVE 609
Cdd:smart00326  12 TAQDPDELSFKKGDIITVLEKSDDGWWKGRLGRGKEGLFPSNYVE 56
SH3_CD2AP-like_1 cd11873
First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This ...
 562-610 1.63e-09

First Src Homology 3 domain (SH3A) of CD2-associated protein and similar proteins; This subfamily is composed of the first SH3 domain (SH3A) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3A of both proteins bind to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic domain of the cell adhesion protein CD2. CIN85 SH3A binds to internal proline-rich motifs within the proline-rich region; this intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. CIN85 SH3A has also been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212806 [Multi-domain]  Cd Length: 53  Bit Score: 54.19  E-value: 1.63e-09
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd11873    6 FDYDAEEPDELTLKVGDIITNVKKMEEGWWEGTLNGKRG-MFPDNFVKV 53
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
 444-518 2.01e-09

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 54.96  E-value: 2.01e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 444 WWHPECTRIAAEEMLKRIPTD-GAFLVRPSERESNCYAISFRAEKKIKHCKIKL--EGRLYTTGTVQFESLVELINYY 518
Cdd:cd10360    2 WYFSGISRTQAQQLLLSPPNEpGAFLIRPSESSLGGYSLSVRAQAKVCHYRICMapSGSLYLQKGRLFPGLEELLAYY 79
SH3_Nck2_2 cd11902
Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth ...
 553-610 2.02e-09

Second Src Homology 3 domain of Nck2 adaptor protein; Nck2 (also called Nckbeta or Growth factor receptor-bound protein 4, Grb4) plays a crucial role in connecting signaling pathways of tyrosine kinase receptors and important effectors in actin dynamics and cytoskeletal remodeling. It binds neuronal signaling proteins such as ephrinB and Disabled-1 (Dab-1) exclusively. Nck adaptor proteins regulate actin cytoskeleton dynamics by linking proline-rich effector molecules to protein tyrosine kinases and phosphorylated signaling intermediates. They contain three SH3 domains and a C-terminal SH2 domain. They function downstream of the PDGFbeta receptor and are involved in Rho GTPase signaling and actin dynamics. Vertebrates contain two Nck adaptor proteins: Nck1 (also called Nckalpha) and Nck2, which show partly overlapping functions but also bind distinct targets. The second SH3 domain of Nck appears to prefer ligands containing the APxxPxR motif. SH3 domains are protein interaction domains that usually bind to proline-rich ligands with moderate affinity and selectivity, preferentially a PxxP motif. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212835 [Multi-domain]  Cd Length: 55  Bit Score: 54.24  E-value: 2.02e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 553 IPGYMdptSFTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd11902    1 IPAFV---KFAYVAEREDELSLVKGSRVTVMEKCSDGWWRGSYNGQIG-WFPSNYVVE 54
SH2_SH2B1 cd10410
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, ...
 329-420 2.06e-09

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, PSM), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198273  Cd Length: 97  Bit Score: 55.41  E-value: 2.06e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 329 GEKWFHGKLARGReeAEELLRHYSYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEmGQTQyylIDTNCFDSL 408
Cdd:cd10410    7 GYPWFHGMLSRLK--AAQLVLEGGTGSHGVFLVRQSETRRGEYVLTFNFQGKAKHLRLSLNEE-GQCR---VQHLWFQSI 80

                         90
                 ....*....|..
gi 307167498 409 YSLITHYRNHPL 420
Cdd:cd10410   81 FDMLEHFRVHPI 92
PHsplit_PLC_gamma cd13234
Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated ...
 266-296 3.57e-09

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. The split PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270054  Cd Length: 105  Bit Score: 55.17  E-value: 3.57e-09
                         10        20        30
                 ....*....|....*....|....*....|.
gi 307167498 266 KNGILYLEDPIDKEWNPHFFVLTQQKLFYTD 296
Cdd:cd13234    3 KNGILYLEDPINHEWYPHFFVLTSNKIYYSE 33
SH2_Nterm_RasGAP cd10353
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 441-518 4.67e-09

N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the N-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198216  Cd Length: 103  Bit Score: 54.84  E-value: 4.67e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 441 EKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTTGTVQFESLVELINYY 518
Cdd:cd10353   18 TNQWYHGRLDRTIAEERLRQAGKLGSYLIRESDRRPGSFVLSFLSRTGVNHFRIIAMCGDYYIGGRRFSSLSDLIGYY 95
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 332-436 4.71e-09

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 54.71  E-value: 4.71e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHySYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIklKQEMGQTqYYLIDTNCFDSLYSL 411
Cdd:cd09938    3 FFYGSITR--EEAEEYLKL-AGMSDGLFLLRQSLRSLGGYVLSVCHGRKFHHYTI--ERQLNGT-YAIAGGKAHCGPAEL 76

                         90       100
                 ....*....|....*....|....*
gi 307167498 412 ITHyrnHPLRSQEFLITLQEPVPQP 436
Cdd:cd09938   77 CEY---HSTDLDGLVCLLRKPCNRP 98
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
 444-518 5.72e-09

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 54.20  E-value: 5.72e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498 444 WWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKI--KLEGRlYTTGTVQFESLVELINYY 518
Cdd:cd09941    5 WFHGKISRAEAEEILMNQRPDGAFLIRESESSPGDFSLSVKFGNDVQHFKVlrDGAGK-YFLWVVKFNSLNELVDYH 80
SH3_alphaPIX cd12060
Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho ...
 562-611 6.16e-09

Src Homology 3 domain of alpha-Pak Interactive eXchange factor; Alpha-PIX, also called Rho guanine nucleotide exchange factor 6 (ARHGEF6) or Cool (Cloned out of Library)-2, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and is localized in dendritic spines where it regulates spine morphogenesis. It controls dendritic length and spine density in the hippocampus. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212993  Cd Length: 58  Bit Score: 53.08  E-value: 6.16e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEEI 611
Cdd:cd12060    8 FNFKQTNEDELSVCKGDIIYVTRVEEGGWWEGTLNGKTG-WFPSNYVREI 56
SH2_SH2B2 cd10411
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), ...
 332-420 6.25e-09

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198274  Cd Length: 97  Bit Score: 54.24  E-value: 6.25e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARGReeAEELLRHYSYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLkQEMGQTQYYLIdtnCFDSLYSL 411
Cdd:cd10411   10 WFHGTLSRVK--AAQLVLAGGPRSHGLFVIRQSETRPGEYVLTFNFQGKAKHLRLSL-NGHGQCHVQHL---WFQSVFDM 83


                 ....*....
gi 307167498 412 ITHYRNHPL 420
Cdd:cd10411   84 LRHFHTHPI 92
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
 332-415 7.09e-09

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 55.03  E-value: 7.09e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLarGREEAEELLRHysylgDGTFLVRQCVTFVGDYCLS-FWrKGKVNH---CRIKLKQEMGQTQY-YLIDTNCFD 406
Cdd:cd10337    8 WYHGRI--PRQVAESLVQR-----EGDFLVRDSLSSPGDYVLTcRW-KGQPLHfkiNRVVLRPSEAYTRVqYQFEDEQFD 79


                 ....*....
gi 307167498 407 SLYSLITHY 415
Cdd:cd10337   80 SIPALVHFY 88
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
 332-435 1.13e-08

Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 53.63  E-value: 1.13e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELL---RHysylgdGTFLVRQCVTFVGDYCLSFWRKGKVNHCRI-KLKQEMGQTQYYLIDTNCFDS 407
Cdd:cd09926    9 WYFGPMSR--QEAQELLqgqRH------GVFLVRDSSTIPGDYVLSVSENSRVSHYIInSLGQPAPNQSRYRIGDQEFDD 80

                         90       100
                 ....*....|....*....|....*...
gi 307167498 408 LYSLITHYRNHPLrsqeFLITLQEPVPQ 435
Cdd:cd09926   81 LPALLEFYKLHYL----DTTTLIEPASR 104
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
 332-419 1.18e-08

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 53.16  E-value: 1.18e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLarGREEAEELLRHysylG-DGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIklkQEMGQTQYYLIDTNCFDSLYS 410
Cdd:cd09935    5 WYHGPI--SRNAAEYLLSS----GiNGSFLVRESESSPGQYSISLRYDGRVYHYRI---SEDSDGKVYVTQEHRFNTLAE 75


                 ....*....
gi 307167498 411 LITHYRNHP 419
Cdd:cd09935   76 LVHHHSKNA 84
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 332-437 1.38e-08

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 53.48  E-value: 1.38e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHYSylgDGTFLVRQCVTFVGDYCLSFwRKGKVNHCrIKLKQEMGqtQYYLIDTNCFDSLYSL 411
Cdd:cd09942    9 WYWGDISR--EEVNEKMRDTP---DGTFLVRDASTMKGDYTLTL-RKGGNNKL-IKIFHRDG--KYGFSDPLTFNSVVEL 79

                         90       100
                 ....*....|....*....|....*...
gi 307167498 412 ITHYRNHPLR--SQEFLITLQEPVPQPN 437
Cdd:cd09942   80 INYYRNNSLAeyNRKLDVKLLYPVSRFQ 107
SH3_betaPIX cd12061
Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho ...
 562-611 2.01e-08

Src Homology 3 domain of beta-Pak Interactive eXchange factor; Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212994 [Multi-domain]  Cd Length: 54  Bit Score: 51.22  E-value: 2.01e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEEI 611
Cdd:cd12061    6 FNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTG-WFPSNYVREI 54
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
 332-424 3.07e-08

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 52.13  E-value: 3.07e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHYSYlgDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMgqtqyYLIDTNCFDSLYSL 411
Cdd:cd09943    3 WYYGRITR--HQAETLLNEHGH--EGDFLIRDSESNPGDYSVSLKAPGRNKHFKVQVVDNV-----YCIGQRKFHTMDEL 73

                         90
                 ....*....|...
gi 307167498 412 ITHYRNHPLRSQE 424
Cdd:cd09943   74 VEHYKKAPIFTSE 86
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 846-930 3.83e-08

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 52.72  E-value: 3.83e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 846 KICLKVIGARHLM-KSGRGTASPSIEVeiigaDFDsGTKLTTKTIPDNgFNPMWNETCEFEIFNPyfALIRFLVQDEDMF 924
Cdd:cd04022    1 KLVVEVVDAQDLMpKDGQGSSSAYVEL-----DFD-GQKKRTRTKPKD-LNPVWNEKLVFNVSDP--SRLSNLVLEVYVY 71


                 ....*.
gi 307167498 925 GDSNFI 930
Cdd:cd04022   72 NDRRSG 77
SH3_CIN85_1 cd12052
First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
 562-610 3.99e-08

First Src Homology 3 domain (SH3A) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CIN85; SH3A binds to internal proline-rich motifs within the proline-rich region. This intramolecular interaction serves as a regulatory mechanism to keep CIN85 in a closed conformation, preventing the recruitment of other proteins. SH3A has also been shown to bind ubiquitin and to an atypical PXXXPR motif at the C-terminus of Cbl and the cytoplasmic end of the cell adhesion protein CD2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212985 [Multi-domain]  Cd Length: 53  Bit Score: 50.66  E-value: 3.99e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd12052    6 FDYKAQHEDELTITVGDIITKIKKDDGGWWEGEIKGRRG-LFPDNFVRE 53
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
 330-418 4.57e-08

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 51.97  E-value: 4.57e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 330 EKWFHGKLARgrEEAEELLRHYSYlGDGTFLVRQCVTFVGDYCLSFW----RKG-KVNHCRIKlkqEMGQTQYYLIDTNC 404
Cdd:cd10365    3 EEWYFGKITR--RESERLLLNAEN-PRGTFLVRESETTKGAYCLSVSdfdnAKGlNVKHYKIR---KLDSGGFYITSRTQ 76

                         90
                 ....*....|....
gi 307167498 405 FDSLYSLITHYRNH 418
Cdd:cd10365   77 FNSLQQLVAYYSKH 90
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
 440-533 4.58e-08

Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine kinase Txk is expressed in thymus, spleen, lymph node, T lymphocytes, NK cells, mast cell lines, and myeloid cell line. Txk plays a role in TCR signal transduction, T cell development, and selection which is analogous to the function of Itk. Txk has been shown to interact with IFN-gamma. Unlike most of the Tec family members Txk lacks a PH domain. Instead Txk has a unique region containing a palmitoylated cysteine string which has a similar membrane tethering function as the PH domain. Txk also has a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP and crucial to the function of the PH domain. It is not present in Txk which is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198261  Cd Length: 106  Bit Score: 51.87  E-value: 4.58e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSeRESNCYAISF--RA----EKKIKHCKIKLE--GRLYTTGTVQFESL 511
Cdd:cd10398    4 EIYEWYHKNITRNQAERLLRQESKEGAFIVRDS-RHLGSYTISVftRArrstEASIKHYQIKKNdsGQWYVAERHLFQSI 82

                         90       100
                 ....*....|....*....|..
gi 307167498 512 VELINYYERRPLYKKIKLSHPV 533
Cdd:cd10398   83 PELIQYHQHNAAGLMSRLRYPV 104
SH3 cd00174
Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction ...
 565-607 4.75e-08

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins play versatile and diverse roles in the cell, including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.


Pssm-ID: 212690 [Multi-domain]  Cd Length: 51  Bit Score: 50.15  E-value: 4.75e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 307167498 565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANY 607
Cdd:cd00174    9 EAQDDDELSFKKGDIITVLEKDDDGWWEGELNGGREGLFPANY 51
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
 329-415 4.82e-08

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 51.93  E-value: 4.82e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 329 GEKWFHGKLarGREEAE-ELLRHysylGD--GTFLVRQCVTFVGDYCLSF--WRKGKVNHCRIKLKQEMGQTQYYLIDTN 403
Cdd:cd10418    2 AEEWYFGKL--GRKDAErQLLSF----GNprGTFLIRESETTKGAYSLSIrdWDDMKGDHVKHYKIRKLDNGGYYITTRA 75

                         90
                 ....*....|..
gi 307167498 404 CFDSLYSLITHY 415
Cdd:cd10418   76 QFETLQQLVQHY 87
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
 332-424 4.89e-08

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 51.50  E-value: 4.89e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRhySYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIkLKQEMGQtqYYLIDTNcFDSLYSL 411
Cdd:cd09941    5 WFHGKISR--AEAEEILM--NQRPDGAFLIRESESSPGDFSLSVKFGNDVQHFKV-LRDGAGK--YFLWVVK-FNSLNEL 76

                         90
                 ....*....|...
gi 307167498 412 ITHYRNHPLRSQE 424
Cdd:cd09941   77 VDYHRTTSVSRNQ 89
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
 438-521 5.03e-08

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 51.37  E-value: 5.03e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 438 KHEEKEWWHPECTRIAAEEMLKRiptDGAFLVRPSERESNC---YAISFRAEKKIKHCKIK-LEGRLYTTGTVQFESLVE 513
Cdd:cd10361    2 DLENEPYYHGLLPREDAEELLKN---DGDFLVRKTEPKGGGkrkLVLSVRWDGKIRHFVINrDDGGKYYIEGKSFKSISE 78


                 ....*...
gi 307167498 514 LINYYERR 521
Cdd:cd10361   79 LINYYQKT 86
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 327-433 5.19e-08

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 51.65  E-value: 5.19e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 327 HFGEK-WFHGKLARGreEAEELLRHYSylgDGTFLVRQCVTfVGDYCLSFWRKGKVNHCRI-KLKQEMGQTQYYlidtNC 404
Cdd:cd09930    2 HHDERtWLVGDINRT--QAEELLRGKP---DGTFLIRESST-QGCYACSVVCNGEVKHCVIyKTETGYGFAEPY----NL 71

                         90       100       110
                 ....*....|....*....|....*....|.
gi 307167498 405 FDSLYSLITHYRNHPL--RSQEFLITLQEPV 433
Cdd:cd09930   72 YESLKELVLHYAHNSLeqHNDSLTVTLAYPV 102
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 326-416 5.93e-08

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 51.65  E-value: 5.93e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 326 LHFGEKWFHGKLARgrEEAEELLRHYSyLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGQTQYYLIDTNC- 404
Cdd:cd09944    1 IHRSQPWFHGGISR--DEAARLIRQQG-LVDGVFLVRESQSNPGAFVLSLKHGQKIKHYQIIPIEDEGQWYFTLDDGVTk 77

                         90
                 ....*....|..
gi 307167498 405 FDSLYSLITHYR 416
Cdd:cd09944   78 FYDLLQLVEFYQ 89
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
 444-520 7.78e-08

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 51.29  E-value: 7.78e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKI--KLEGRL--YTTGTVQ---FESLVELIN 516
Cdd:cd10343    5 WYHGNITRSKAEELLSKAGKDGSFLVRDSESVSGAYALCVLYQNCVHTYRIlpNAEDKLsvQASEGVPvrfFTTLPELIE 84


                 ....
gi 307167498 517 YYER 520
Cdd:cd10343   85 FYQK 88
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 849-933 7.91e-08

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 52.04  E-value: 7.91e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 849 LKVIGARHLMKSGRGTASPSIEVEII--GAdfdsgTKLTTKTIPdNGFNPMWNETCEFEIFNPYFALIRFLVQDEDMFGD 926
Cdd:cd04024    5 VHVVEAKDLAAKDRSGKGKSDPYAILsvGA-----QRFKTQTIP-NTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAG 78


                 ....*..
gi 307167498 927 SNFIGQA 933
Cdd:cd04024   79 KDYLGEF 85
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 439-535 9.37e-08

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 51.27  E-value: 9.37e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 439 HEEKEWWHPECTRIAAEEMLKRI-PTDGAFLVRPSERESNCYAISFRAEKKIKHCKI---KLEGRLYTT---GTVQFESL 511
Cdd:cd09944    2 HRSQPWFHGGISRDEAARLIRQQgLVDGVFLVRESQSNPGAFVLSLKHGQKIKHYQIipiEDEGQWYFTlddGVTKFYDL 81

                         90       100
                 ....*....|....*....|....
gi 307167498 512 VELINYYERRPLYKKIKLSHPVNQ 535
Cdd:cd09944   82 LQLVEFYQLNAGSLPTRLKHYCTR 105
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
 444-533 9.93e-08

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 50.89  E-value: 9.93e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLkRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKI-KLEGRLYTTG--TVQFESLVELINYYER 520
Cdd:cd09945    3 WYHGAITRIEAESLL-RPCKEGSYLVRNSESTKQDYSLSLKSAKGFMHMRIqRNETGQYILGqfSRPFETIPEMIRHYCL 81

                         90
                 ....*....|....*..
gi 307167498 521 RPLYKK----IKLSHPV 533
Cdd:cd09945   82 NKLPVRgaehMCLLEPV 98
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 332-415 1.12e-07

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 50.11  E-value: 1.12e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHYSyLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEmgqtQYYLIDTN-CFDSLYS 410
Cdd:cd10348    2 WLHGALDR--NEAVEILKQKA-DADGSFLVRYSRRRPGGYVLTLVYENHVYHFEIQNRDD----KWFYIDDGpYFESLEH 74


                 ....*
gi 307167498 411 LITHY 415
Cdd:cd10348   75 LIEHY 79
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
 440-520 1.19e-07

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 50.82  E-value: 1.19e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAEEMLKRIPTD-GAFLVRPSERESNCYAIS---FRAEK--KIKHCKI-KLE-GRLYTTGTVQFESL 511
Cdd:cd10365    1 QAEEWYFGKITRRESERLLLNAENPrGTFLVRESETTKGAYCLSvsdFDNAKglNVKHYKIrKLDsGGFYITSRTQFNSL 80


                 ....*....
gi 307167498 512 VELINYYER 520
Cdd:cd10365   81 QQLVAYYSK 89
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
 329-415 1.29e-07

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 50.41  E-value: 1.29e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 329 GEKWFHGKLarGREEAEELLRHYsylGD--GTFLVRQCVTFVGDYCLSF--WRKGKVNHCRIKLKQEMGQTQYYLIDTNC 404
Cdd:cd10368    2 AEEWYFGKL--GRKDAERQLLSF---GNprGTFLIRESETTKGAYSLSIrdWDDMKGDHVKHYKIRKLDNGGYYITTRAQ 76

                         90
                 ....*....|.
gi 307167498 405 FDSLYSLITHY 415
Cdd:cd10368   77 FETLQQLVQHY 87
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
 327-418 1.53e-07

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 49.83  E-value: 1.53e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 327 HFGEKWFHGklARGREEAEELLRHysylgDGTFLVR---QCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGqtqyYLIDTN 403
Cdd:cd10361    3 LENEPYYHG--LLPREDAEELLKN-----DGDFLVRktePKGGGKRKLVLSVRWDGKIRHFVINRDDGGK----YYIEGK 71

                         90
                 ....*....|....*
gi 307167498 404 CFDSLYSLITHYRNH 418
Cdd:cd10361   72 SFKSISELINYYQKT 86
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 849-949 1.56e-07

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 50.64  E-value: 1.56e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 849 LKVIGARHLMKSGRGTAS-PSIEVEIIGADFdsgtkLTTKTIPDNgFNPMWNETCEFEIFNPYFALIRFLVQDEDMFGDS 927
Cdd:cd04040    3 VDVISAENLPSADRNGKSdPFVKFYLNGEKV-----FKTKTIKKT-LNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKD 76

                         90       100
                 ....*....|....*....|....*
gi 307167498 928 NFIGQATYPVRCL---RTGYRSVPL 949
Cdd:cd04040   77 DLLGSAYIDLSDLepeETTELTLPL 101
SH3_Nostrin cd11823
Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in ...
 565-610 1.58e-07

Src homology 3 domain of Nitric Oxide Synthase TRaffic INducer; Nostrin is expressed in endothelial and epithelial cells and is involved in the regulation, trafficking and targeting of endothelial NOS (eNOS). It facilitates the endocytosis of eNOS by coordinating the functions of dynamin and the Wiskott-Aldrich syndrome protein (WASP). Increased expression of Nostrin may be correlated to preeclampsia. Nostrin contains an N-terminal F-BAR domain and a C-terminal SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212757 [Multi-domain]  Cd Length: 53  Bit Score: 48.88  E-value: 1.58e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 307167498 565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHwFPANYVEE 610
Cdd:cd11823    9 TANREDELSLQPGDIIEVHEKQDDGWWLGELNGKKGI-FPATYVEE 53
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 440-533 2.12e-07

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 50.01  E-value: 2.12e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAEEMLKRIPtDGAFLVRPSERESNCYAISFR---AEKKIKHCKikLEGRLYTTGTVQFESLVELIN 516
Cdd:cd09942    5 QEAEWYWGDISREEVNEKMRDTP-DGTFLVRDASTMKGDYTLTLRkggNNKLIKIFH--RDGKYGFSDPLTFNSVVELIN 81

                         90       100
                 ....*....|....*....|..
gi 307167498 517 YYERRPL--YKK---IKLSHPV 533
Cdd:cd09942   82 YYRNNSLaeYNRkldVKLLYPV 103
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
 444-523 2.22e-07

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198270  Cd Length: 103  Bit Score: 50.00  E-value: 2.22e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAE-EMLKRIptDGAFLVRPSERESNCYAISFRAEKKIKHCKI-KLEGRLYTTGTVQFESLVELINYYERR 521
Cdd:cd10407    7 WYAGAMERLQAEtELINRV--NSTYLVRHRTKESGEYAISIKYNNEVKHIKIlTRDGFFHIAENRKFKSLMELVEYYKHH 84


                 ..
gi 307167498 522 PL 523
Cdd:cd10407   85 SL 86
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
 332-418 2.46e-07

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 49.71  E-value: 2.46e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHYSylGDGTFLVRQCVTfVGDYCLSFWRK----GKVNHCRIKlkqEMGQTQYYLIDTNCFDS 407
Cdd:cd09934    8 WYVGDMSR--QRAESLLKQED--KEGCFVVRNSST-KGLYTVSLFTKvpgsPHVKHYHIK---QNARSEFYLAEKHCFET 79

                         90
                 ....*....|.
gi 307167498 408 LYSLItHYRNH 418
Cdd:cd09934   80 IPELI-NYHQH 89
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
 440-533 2.61e-07

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 49.71  E-value: 2.61e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSeRESNCYAISF----RAEKKIKHCKIKL--EGRLYTTGTVQFESLVE 513
Cdd:cd09934    4 EKYEWYVGDMSRQRAESLLKQEDKEGCFVVRNS-STKGLYTVSLftkvPGSPHVKHYHIKQnaRSEFYLAEKHCFETIPE 82

                         90       100
                 ....*....|....*....|
gi 307167498 514 LINYYERRPLYKKIKLSHPV 533
Cdd:cd09934   83 LINYHQHNSGGLATRLKYPV 102
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
 443-532 2.98e-07

Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk); Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. PTK6 (9). PTK6 contains a SH3 domain, a SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain. The structure of the SH2 domain resembles other SH2 domains except for a centrally located four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD). There are also differences in the loop length which might be responsible for PTK6 ligand specificity. There are two possible means of regulation of PTK6: autoinhibitory with the phosphorylation of Tyr playing a role in its negative regulation and autophosphorylation at this site, though it has been shown that PTK6 might phosphorylate signal transduction-associated proteins Sam68 and signal transducing adaptor family member 2 (STAP/BKS) in vivo. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198221  Cd Length: 100  Bit Score: 49.36  E-value: 2.98e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 443 EWWHPECtrIAAEEMLKRIPTD----GAFLVRPSERESNCYAISFRAEKKIKHCKI--KLEGRLYTTGTVQFESLVELIN 516
Cdd:cd10358    2 EPWFFGC--ISRSEAVRRLQAEgnatGAFLIRVSEKPSADYVLSVRDTQAVRHYKIwrRAGGRLHLNEAVSFLSLPELVN 79

                         90
                 ....*....|....*.
gi 307167498 517 YYERRPLYKKIKLSHP 532
Cdd:cd10358   80 YHRAQSLSHGLRLAAP 95
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 846-967 3.00e-07

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 50.18  E-value: 3.00e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 846 KICLKVIGARHLMKSGR-GTASPSIEVeiigadFDSGTKLTTKTIPDNGFnPMWNETCEFEIFNPYFALIRFLVQDEDMF 924
Cdd:cd04025    1 RLRCHVLEARDLAPKDRnGTSDPFVRV------FYNGQTLETSVVKKSCY-PRWNEVFEFELMEGADSPLSVEVWDWDLV 73

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 307167498 925 GDSNFIGQATYPVRCLRTG------YRSVPLKNVYSEDL-ELASLLVHIK 967
Cdd:cd04025   74 SKNDFLGKVVFSIQTLQQAkqeegwFRLLPDPRAEEESGgNLGSLRLKVR 123
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
 439-531 3.61e-07

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198277  Cd Length: 108  Bit Score: 49.54  E-value: 3.61e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 439 HEEKEWWHPECTRIAAEEM-LKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKI---KLEGRLYTT---GTVQFESL 511
Cdd:cd10414    2 HRSQPWFHHKISRDEAQRLiIQQGLVDGVFLVRDSQSNPRTFVLSMSHGQKIKHFQIipvEDDGELFHTlddGHTRFTDL 81

                         90       100
                 ....*....|....*....|
gi 307167498 512 VELINYYERRPLYKKIKLSH 531
Cdd:cd10414   82 IQLVEFYQLNKGVLPCKLKH 101
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
 332-433 3.92e-07

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 48.96  E-value: 3.92e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARGreEAEELLRhysYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIklkQEMGQTQYYLIDTN-CFDSLYS 410
Cdd:cd09945    3 WYHGAITRI--EAESLLR---PCKEGSYLVRNSESTKQDYSLSLKSAKGFMHMRI---QRNETGQYILGQFSrPFETIPE 74

                         90       100
                 ....*....|....*....|....*
gi 307167498 411 LITHYRNH--PLRSQEFLiTLQEPV 433
Cdd:cd09945   75 MIRHYCLNklPVRGAEHM-CLLEPV 98
SH3_Intersectin_5 cd11840
Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor ...
 562-610 3.95e-07

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212774 [Multi-domain]  Cd Length: 53  Bit Score: 47.80  E-value: 3.95e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGkKQHWFPANYVEE 610
Cdd:cd11840    6 FPYTAQNEDELSFQKGDIINVLSKDDPDWWRGELNG-QTGLFPSNYVEP 53
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 331-424 4.47e-07

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198271  Cd Length: 97  Bit Score: 48.87  E-value: 4.47e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 331 KWFHGKLARgrEEAEELLRHYSYLGDgtFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMgqtqyYLIDTNCFDSLYS 410
Cdd:cd10408    2 PWYYGKVTR--HQAEMALNERGNEGD--FLIRDSESSPNDFSVSLKAQGKNKHFKVQLKECV-----YCIGQRKFSSMEE 72

                         90
                 ....*....|....
gi 307167498 411 LITHYRNHPLRSQE 424
Cdd:cd10408   73 LVEHYKKAPIFTSE 86
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
 444-529 4.82e-07

Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198269  Cd Length: 103  Bit Score: 48.91  E-value: 4.82e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLKRiPTDGAFLVRPSERESNCYAISFRAEKKIKHCK-IKLEGRLYTTGTVQFESLVELINYYERRP 522
Cdd:cd10406    7 WFAGNMERQQTDNLLKS-HASGTYLIRERPAEAERFAISIKFNDEVKHIKvVEKDNWIHITEAKKFESLLELVEYYQCHS 85


                 ....*..
gi 307167498 523 LYKKIKL 529
Cdd:cd10406   86 LKESFKQ 92
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
 333-413 5.28e-07

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 48.51  E-value: 5.28e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 333 FHGKLarGREEAEELLRHYSylgDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKqemGQTQYYLIDTNCFDSLYSLI 412
Cdd:cd10352    9 YHGLI--SREEAEQLLSGAS---DGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYD---GKNHYHYVGEKRFDTIHDLV 80


                 .
gi 307167498 413 T 413
Cdd:cd10352   81 A 81
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
 332-436 7.57e-07

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198264  Cd Length: 99  Bit Score: 48.35  E-value: 7.57e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLArgREEAEELLRHYSYLgDGTFLVRQCVTfVGDYCLSFWRKGKVNHCRIKlKQEMGQTQyyLIDTNCFDSLYSL 411
Cdd:cd10401    5 WFHGKIS--REESEQILLIGSKT-NGKFLIRERDN-NGSYALCLLHDGKVLHYRID-KDKTGKLS--IPDGKKFDTLWQL 77

                         90       100
                 ....*....|....*....|....*
gi 307167498 412 ITHYRNHPlrsQEFLITLQEPVPQP 436
Cdd:cd10401   78 VEHYSYKP---DGLLRVLTEPCPRI 99
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
 330-418 7.95e-07

Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine kinase Bmx is expressed in the endothelium of large arteries, fetal endocardium, adult endocardium of the left ventricle, bone marrow, lung, testis, granulocytes, myeloid cell lines, and prostate cell lines. Bmx is involved in the regulation of Rho and serum response factor (SRF). Bmx has been shown to interact with PAK1, PTK2, PTPN21, and RUFY1. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains. It is not present in Txk and the type 1 splice form of the Drosophila homolog. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198262  Cd Length: 106  Bit Score: 48.41  E-value: 7.95e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 330 EKWFHGKLARGreEAEELLRHYSylGDGTFLVRQCvTFVGDYCLSFW------RKGKVNHCRIKLKQEmgqTQYYLIDTN 403
Cdd:cd10399    6 YDWFAGNISRS--QSEQLLRQKG--KEGAFMVRNS-SQVGMYTVSLFskavndKKGTVKHYHVHTNAE---NKLYLAENY 77

                         90
                 ....*....|....*
gi 307167498 404 CFDSLYSLItHYRNH 418
Cdd:cd10399   78 CFDSIPKLI-HYHQH 91
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
 440-522 8.59e-07

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 47.88  E-value: 8.59e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAEEMLkRIPTD--GAFLVRPSERESNCYAISFRAEKKIKHCKIKL--EGRLYTTGTVQFESLVELI 515
Cdd:cd10370    1 EAEPWYFGKIKRIEAEKKL-LLPENehGAFLIRDSESRHNDYSLSVRDGDTVKHYRIRQldEGGFFIARRTTFRTLQELV 79


                 ....*..
gi 307167498 516 NYYERRP 522
Cdd:cd10370   80 EHYSKDS 86
SH3_1 pfam00018
SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal ...
 565-605 1.05e-06

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 394975 [Multi-domain]  Cd Length: 47  Bit Score: 46.04  E-value: 1.05e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 307167498  565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPA 605
Cdd:pfam00018   7 TAQEPDELSFKKGDIIIVLEKSEDGWWKGRNKGGKEGLIPS 47
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
 436-518 1.06e-06

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 47.87  E-value: 1.06e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 436 PNKHEEK---EWWHPECTRIAAEEMLkRIPTD--GAFLVRPSERESNCYAISFR-----AEKKIKHCKI-KLE-GRLYTT 503
Cdd:cd10344    1 PSNYVAKvyhGWLFEGLSREKAEELL-MLPGNqvGSFLIRESETRRGCYSLSVRhrgsqSRDSVKHYRIfRLDnGWFYIS 79

                         90
                 ....*....|....*
gi 307167498 504 GTVQFESLVELINYY 518
Cdd:cd10344   80 PRLTFQCLEDMVNHY 94
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
 444-529 1.06e-06

Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav1 plays a role in T-cell and B-cell development and activation. It has been identified as the specific binding partner of Nef proteins from HIV-1, resulting in morphological changes, cytoskeletal rearrangements, and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Vav1 has been shown to interact with Ku70, PLCG1, Lymphocyte cytosolic protein 2, Janus kinase 2, SIAH2, S100B, Abl gene, ARHGDIB, SHB, PIK3R1, PRKCQ, Grb2, MAPK1, Syk, Linker of activated T cells, Cbl gene and EZH2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198268  Cd Length: 103  Bit Score: 48.09  E-value: 1.06e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLKRiPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLY-TTGTVQFESLVELINYYERRP 522
Cdd:cd10405    7 WYAGPMERAGAESILAN-RSDGTYLVRQRVKDAAEFAISIKYNVEVKHIKIMTAEGLYrITEKKAFRGLTELVEFYQQNS 85


                 ....*..
gi 307167498 523 LYKKIKL 529
Cdd:cd10405   86 LKDCFKS 92
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
 444-517 1.09e-06

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198179  Cd Length: 104  Bit Score: 48.11  E-value: 1.09e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 307167498 444 WWHPECTRIAAEEMLKripTDGAFLVRPSERESNCYAISFRAEKKIKH-CKIKLEGRLYTTGTVqFESLVELINY 517
Cdd:cd09925    9 WYHGKMSRRDAESLLQ---TDGDFLVRESTTTPGQYVLTGMQNGQPKHlLLVDPEGVVRTKDRV-FESISHLINY 79
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
 444-520 1.12e-06

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 47.67  E-value: 1.12e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 444 WWHPECTRIAAEEMLKRiPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIK-LEGRLYTTGTVQFESLVELINYYER 520
Cdd:cd09937    5 WFHGKISREEAERLLQP-PEDGLFLVRESTNYPGDYTLCVSFEGKVEHYRVIyRNGKLTIDEEEYFENLIQLVEHYTK 81
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
 443-523 1.12e-06

Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function as an adapter protein involved in tyrosine kinase signaling. It may also be involved in regulating cytokine signaling and cytoskeletal reorganization in hematopoietic cells. HSH2 contains several putative protein-binding motifs, SH3-binding proline-rich regions, and phosphotyrosine sites, but lacks enzymatic motifs. HSH2 was found to interact with cytokine-regulated tyrosine kinase c-FES and an activated Cdc42-associated tyrosine kinase ACK1. HSH2 binds c-FES through both its C-terminal region and its N-terminal region including the SH2 domain and binds ACK1 via its N-terminal proline-rich region. Both kinases bound and tyrosine-phosphorylated HSH2 in mammalian cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198199  Cd Length: 102  Bit Score: 47.96  E-value: 1.12e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 443 EWWHPECTRIAAEEMLKRIPTdGAFLVRPSERESNcYAISFRAEKKIKHCKIKL--EGRLYTTGT-VQFESLVELINYYE 519
Cdd:cd09946    8 EWFHGAISREAAENMLESQPL-GSFLIRVSHSHVG-YTLSYKAQSSCRHFMVKLldDGTFMIPGEkVAHTSLHALVTFHQ 85


                 ....
gi 307167498 520 RRPL 523
Cdd:cd09946   86 QKPI 89
PI-PLCc_bacteria_like cd08557
Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...
 92-188 1.14e-06

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar proteins; This subfamily corresponds to the catalytic domain present in bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13) and their sequence homologs found in eukaryota. Bacterial PI-PLCs participate in Ca2+-independent PI metabolism, hydrolyzing the membrane lipid phosphatidylinositol (PI) to produce phosphorylated myo-inositol and diacylglycerol (DAG). Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. Bacterial PI-PLCs contain a single TIM-barrel type catalytic domain. Its catalytic mechanism is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. Eukaryotic homologs in this family are named as phosphatidylinositol-specific phospholipase C X domain containing proteins (PI-PLCXD). They are distinct from the typical eukaryotic phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11), which have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. The catalytic core domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. In contrast, eukaryotic PI-PLCXDs contain a single TIM-barrel type catalytic domain, X domain, which is closely related to that of bacterial PI-PLCs. Although the biological function of eukaryotic PI-PLCXDs still remains unclear, it may be distinct from that of typical eukaryotic PI-PLCs. This family also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host's immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.


Pssm-ID: 176500 [Multi-domain]  Cd Length: 271  Bit Score: 51.32  E-value: 1.14e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498  92 SQDMARPLAHYWIASSHNTY-----LMGDQISSESSCQAY--VRALRAGCRCIELDCWDGPDGMPF-IFHGHTLTTKIKF 163
Cdd:cd08557    2 ALLDDLPLSQLSIPGTHNSYaytidGNSPIVSKWSKTQDLsiTDQLDAGVRYLDLRVAYDPDDGDLyVCHGLFLLNGQTL 81

                         90       100
                 ....*....|....*....|....*..
gi 307167498 164 LDVIKTIKehAF--ATSEYPVILSIED 188
Cdd:cd08557   82 EDVLNEVK--DFldAHPSEVVILDLEH 106
SH2_SHF cd10392
Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought ...
 444-533 1.42e-06

Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought to play a role in PDGF-receptor signaling and regulation of apoptosis. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198255  Cd Length: 98  Bit Score: 47.37  E-value: 1.42e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLkRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKI-KLEGRLYTTG--TVQFESLVELINYYER 520
Cdd:cd10392    3 WYHGAISRTDAENLL-RLCKEASYLVRNSETSKNDFSLSLKSSQGFMHMKLsRTKEHKYVLGqnSPPFSSVPEIIHHYAS 81

                         90
                 ....*....|....*..
gi 307167498 521 RPLYKK----IKLSHPV 533
Cdd:cd10392   82 RKLPIKgaehMSLLYPV 98
SH3_Cortactin_like cd11819
Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, ...
 566-609 1.54e-06

Src homology 3 domain of Cortactin and related proteins; This subfamily includes cortactin, Abp1 (actin-binding protein 1), hematopoietic lineage cell-specific protein 1 (HS1), and similar proteins. These proteins are involved in regulating actin dynamics through direct or indirect interaction with the Arp2/3 complex, which is required to initiate actin polymerization. They all contain at least one C-terminal SH3 domain. Cortactin and HS1 bind Arp2/3 and actin through an N-terminal region that contains an acidic domain and several copies of a repeat domain found in cortactin and HS1. Abp1 binds actin via an N-terminal actin-depolymerizing factor (ADF) homology domain. Yeast Abp1 binds Arp2/3 directly through two acidic domains. Mammalian Abp1 does not directly interact with Arp2/3; instead, it regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. The C-terminal region of these proteins acts as an adaptor or scaffold that can connect membrane trafficking and signaling proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212753 [Multi-domain]  Cd Length: 54  Bit Score: 46.15  E-value: 1.54e-06
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 307167498 566 AKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYVE 609
Cdd:cd11819   10 AAEDNEISFVEGDIITQIEQIDEGWWLGVNAKGQKGLFPANYVE 53
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
 440-521 1.92e-06

Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in the hematopoietic cells, in neural tissues, liver, and adipose tissue. There are two alternatively spliced forms of Lyn. Lyn plays an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation, triggering a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phospholipase C2 (PLC2) and phosphatidyl inositol-3 kinase. These kinases play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FC RIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1 which further down modulate signaling pathways, attenuate cell activation and can mediate tolerance. Lyn also plays a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1) leading to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. It is the primary Src family member involved in signaling downstream of the B cell receptor. Lyn plays an unusual, 2-fold role in B cell receptor signaling; it is essential for initiation of signaling but is also later involved in negative regulation of the signal. Lyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198227  Cd Length: 101  Bit Score: 47.29  E-value: 1.92e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAE-EMLKRIPTDGAFLVRPSERESNCYAISFR-----AEKKIKHCKIKL--EGRLYTTGTVQFESL 511
Cdd:cd10364    1 ETEEWFFKDITRKDAErQLLAPGNSAGAFLIRESETLKGSYSLSVRdydpqHGDVIKHYKIRSldNGGYYISPRITFPCI 80

                         90
                 ....*....|
gi 307167498 512 VELINYYERR 521
Cdd:cd10364   81 SDMIKHYQKQ 90
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
 444-523 2.75e-06

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199832  Cd Length: 102  Bit Score: 46.81  E-value: 2.75e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLKRiPTDGAFLVRPSERESNcYAISFRAEKKIKHCKI-KLEGRLYTTG--TVQFESLVELINYYER 520
Cdd:cd10417    9 WFHGFITRKQTEQLLRD-KALGSFLIRLSDRATG-YILSYRGSDRCRHFVInQLRNRRYLISgdTSSHSTLAELVRHYQE 86


                 ...
gi 307167498 521 RPL 523
Cdd:cd10417   87 VQL 89
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
 329-415 2.88e-06

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 46.59  E-value: 2.88e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 329 GEKWFHGKLarGREEAEELLRHYSYlGDGTFLVRQCVTFVGDYCLSF--WRKGKVNHCRIKLKQEMGQTQYYLIDTNCFD 406
Cdd:cd10419    2 AEEWYFGKL--GRKDAERQLLSFGN-PRGTFLIRESETTKGAYSLSIrdWDDMKGDHVKHYKIRKLDNGGYYITTRAQFE 78


                 ....*....
gi 307167498 407 SLYSLITHY 415
Cdd:cd10419   79 TLQQLVQHY 87
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
 440-520 3.13e-06

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198225  Cd Length: 101  Bit Score: 46.79  E-value: 3.13e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTR-IAAEEMLKRIPTDGAFLVRPSERESNCYAISFR-----AEKKIKHCKIKL--EGRLYTTGTVQFESL 511
Cdd:cd10362    1 EPEPWFFKNLSRnDAERQLLAPGNTHGSFLIRESETTAGSFSLSVRdfdqnQGEVVKHYKIRNldNGGFYISPRITFPGL 80


                 ....*....
gi 307167498 512 VELINYYER 520
Cdd:cd10362   81 HELVRHYTN 89
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
 443-518 3.78e-06

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198178  Cd Length: 81  Bit Score: 45.65  E-value: 3.78e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 443 EWWHPECTRIAAEEMLKRIPtDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEG---RLY--TTGTVQFESLVELINY 517
Cdd:cd09923    1 GWYWGGITRYEAEELLAGKP-EGTFLVRDSSDSRYLFSVSFRTYGRTLHARIEYSNgrfSFDssDPSVPRFPCVVELIEH 79


                 .
gi 307167498 518 Y 518
Cdd:cd09923   80 Y 80
SH2_Nterm_RasGAP cd10353
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 308-415 3.97e-06

N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the N-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198216  Cd Length: 103  Bit Score: 46.36  E-value: 3.97e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 308 DDEESGIRRSSDGAPNDElhfgekWFHGKLarGREEAEELLRHYSYLGdgTFLVRQCVTFVGDYCLSFWRKGKVNHCRIk 387
Cdd:cd10353    3 EYEEEEVAIPLTAPPTNQ------WYHGRL--DRTIAEERLRQAGKLG--SYLIRESDRRPGSFVLSFLSRTGVNHFRI- 71

                         90       100
                 ....*....|....*....|....*...
gi 307167498 388 lkqeMGQTQYYLIDTNCFDSLYSLITHY 415
Cdd:cd10353   72 ----IAMCGDYYIGGRRFSSLSDLIGYY 95
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 443-520 4.02e-06

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 45.88  E-value: 4.02e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 443 EWWHPECTRIAAEEMLK-RIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGR--LYTTGTVQFESLVELINYYE 519
Cdd:cd10348    1 QWLHGALDRNEAVEILKqKADADGSFLVRYSRRRPGGYVLTLVYENHVYHFEIQNRDDkwFYIDDGPYFESLEHLIEHYT 80


                 .
gi 307167498 520 R 520
Cdd:cd10348   81 Q 81
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 444-518 4.85e-06

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 45.45  E-value: 4.85e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 307167498 444 WWHPECTRIAAEEMLKRI-PTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGR---LYTTGTVQFESLVELINYY 518
Cdd:cd10347    3 WYHGKISREVAEALLLREgGRDGLFLVRESTSAPGDYVLSLLAQGEVLHYQIRRHGEdafFSDDGPLIFHGLDTLIEHY 81
SH2_SOCS6 cd10387
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 444-516 5.08e-06

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198250  Cd Length: 100  Bit Score: 45.98  E-value: 5.08e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498 444 WWHPeCTRIAAEEMLKRIPtDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEG---RLYTTGTVQ-FESLVELIN 516
Cdd:cd10387   13 YWGP-ITRWEAEGKLANVP-DGSFLVRDSSDDRYLLSLSFRSHGKTLHTRIEHSNgrfSFYEQPDVEgHTSIVDLIE 87
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
 442-521 5.59e-06

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 45.79  E-value: 5.59e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 442 KEWWHPECTRIAAEEMLKRIPTD-GAFLVRPSERESNCYAISFR-----AEKKIKHCKI-KLE-GRLYTTGTVQFESLVE 513
Cdd:cd10368    3 EEWYFGKLGRKDAERQLLSFGNPrGTFLIRESETTKGAYSLSIRdwddmKGDHVKHYKIrKLDnGGYYITTRAQFETLQQ 82


                 ....*...
gi 307167498 514 LINYYERR 521
Cdd:cd10368   83 LVQHYSET 90
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
 440-521 5.98e-06

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 45.76  E-value: 5.98e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAE-EMLKRIPTDGAFLVRPSERESNCYAISFRA--EKK---IKHCKI-KLE-GRLYTTGTVQFESL 511
Cdd:cd10418    1 QAEEWYFGKLGRKDAErQLLSFGNPRGTFLIRESETTKGAYSLSIRDwdDMKgdhVKHYKIrKLDnGGYYITTRAQFETL 80

                         90
                 ....*....|
gi 307167498 512 VELINYYERR 521
Cdd:cd10418   81 QQLVQHYSER 90
SH2_STAP_family cd09939
Src homology 2 domain found in Signal-transducing adaptor protein (STAP) family; STAP1 and ...
 447-518 6.81e-06

Src homology 2 domain found in Signal-transducing adaptor protein (STAP) family; STAP1 and STAP2 are signal-transducing adaptor proteins. They are composed of a Pleckstrin homology (PH) and SH2 domains along with several tyrosine phosphorylation sites. STAP-1 is an ortholog of BRDG1 (BCR downstream signaling 1). STAP1 protein functions as a docking protein acting downstream of Tec tyrosine kinase in B cell antigen receptor signaling. The protein is phosphorylated by Tec and participates in a positive feedback loop, increasing Tec activity. STAP1 has been shown to interact with C19orf2, an unconventional prefoldin RPB5 interactor. The STAP2 protein is the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase that mediates the interactions linking proteins involved in signal transduction pathways. STAP2 has alternative splicing variants. STAP2 has been shown to interact with tyrosine-protein kinase 6 (PTK6). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198192  Cd Length: 94  Bit Score: 45.61  E-value: 6.81e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 447 PEC----TRIAAEEMLKRIPTDGAFLVRPSeRESNCYAISFRAE---KKIKHCKIKLEGRLYTTGTVQ---FESLVELIN 516
Cdd:cd09939    1 PACfytvSRKEATELLERNPSCGNMLLRPG-SDSRNYSVTTRQEiniPVIRHYKVMSVGQNYTIELEKpvtCPNLFSVIN 79


                 ..
gi 307167498 517 YY 518
Cdd:cd09939   80 YF 81
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
 332-420 6.98e-06

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198218  Cd Length: 92  Bit Score: 45.16  E-value: 6.98e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHYSylGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLkqemgQTQYYLIDTNCFDSLYSL 411
Cdd:cd10355    8 WYHGNLTR--HAAEALLLSNG--VDGSYLLRNSNEGTGLFSLSVRAKDSVKHFHVEY-----TGYSFKFGFNEFSSLQDF 78


                 ....*....
gi 307167498 412 ITHYRNHPL 420
Cdd:cd10355   79 VKHFANQPL 87
EFh_PI-PLCgamma2 cd16215
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; PI-PLC-gamma2, also termed ...
 23-80 7.07e-06

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; PI-PLC-gamma2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2, or phospholipase C-IV (PLC-IV), or phospholipase C-gamma-2 (PLC-gamma-2), is highly expressed in cells of hematopoietic origin. It has been implicated in cell motility important to invasion and dissemination of tumor cells. As an important component of the B cell receptor (BCR) signaling pathway, PI-PLC-gamma2 is required for efficient formation of germinal center (GC) and memory B cells. It works as a critical effector stimulating the increase of intracellular Ca2+ and activates various signaling pathways downstream of the BCR. Moreover, PI-PLC-gamma2 has been implicated in Fc receptor-mediated degranulation of mast cells, integrin signaling in platelets, as well as integrin and Fc receptor-mediated neutrophil functions. It also acts as a crucial signaling mediator modifying DC gene expression program to activate DC responses to beta-glucan-containing pathogens. PI-PLC-gamma2 contains an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Besides, PI-PLC-gamma2 has a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region, which are present within this linker. PI-PLC-gamma2 is activated by receptor and non-receptor tyrosine kinases via its two SH2 and a single SH3 domain. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase.


Pssm-ID: 320045  Cd Length: 154  Bit Score: 47.15  E-value: 7.07e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498  23 VTLQEFQNFLLTEQQDSLGNNELEISRFIREYLQDPQRDIQEPYFTFSEFVDFLFSKQ 80
Cdd:cd16215   97 VHLHDFQRFLVHEQKESWAQDLNKVRERMTKFIDDTMRETAEPFLFVDEFLTYLFSKE 154
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 332-433 7.27e-06

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 45.47  E-value: 7.27e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHYSYlgDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIklkQEMGQTqYYLIDTNCFDSLYSL 411
Cdd:cd10340    2 WFHPVISG--IEAENLLKTRGV--DGSFLARPSKSNPGDFTLSVRRGDEVTHIKI---QNTGDY-YDLYGGEKFATLSEL 73

                         90       100
                 ....*....|....*....|....*
gi 307167498 412 ITHYRNHPLRSQE---FLITLQEPV 433
Cdd:cd10340   74 VQYYMEQHGQLREkngDVIELKYPL 98
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
 330-415 8.81e-06

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 45.28  E-value: 8.81e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 330 EKWFHGKLarGREEAE-ELLRHYSylGDGTFLVRQCVTFVGDYCLSF--W---RKGKVNHCRIKlKQEMGqtQYYLIDTN 403
Cdd:cd10367    3 EEWYFGKI--GRKDAErQLLSPGN--PRGAFLIRESETTKGAYSLSIrdWdqnRGDHVKHYKIR-KLDTG--GYYITTRA 75

                         90
                 ....*....|..
gi 307167498 404 CFDSLYSLITHY 415
Cdd:cd10367   76 QFDTVQELVQHY 87
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 439-522 9.13e-06

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 45.30  E-value: 9.13e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 439 HEEKEWWHPECTRIAAEEML-KRIPTDGAFLVRPsERESNCYAISFRAEKKIKHCKIKLE--GRLYTTGTVQFESLVELI 515
Cdd:cd10402    7 HERMPWYHGSIARDEAERRLySGAQPDGKFLLRE-RKESGTYALSLVYGKTVYHYRIDQDksGKYSIPEGTKFDTLWQLV 85


                 ....*..
gi 307167498 516 NYYERRP 522
Cdd:cd10402   86 EYLKLKP 92
EFh_PI-PLCgamma1_like cd16216
EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like ...
 23-80 9.92e-06

EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like proteins; This family corresponds to a small group of uncharacterized 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like (PI-PLC-gamma1-like) proteins. Although their biological function remains unclear, they shows high sequence similarity with other phosphoinositide phospholipase C gamma proteins. They contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. A second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker.


Pssm-ID: 320046  Cd Length: 150  Bit Score: 46.46  E-value: 9.92e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498  23 VTLQEFQNFLLTEQQDSLGNNELEISRFIREYLQDPQRDIQEPYFTFSEFVDFLFSKQ 80
Cdd:cd16216   93 ISLYDFQKFLQHDQKESWASDVGRVRDYLCGYLKESSNEAPEPSLQLDEFLTYLFSKE 150
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
 441-532 1.02e-05

Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src non-receptor type tyrosine kinase family of proteins. Blk is expressed in the B-cells. Unlike most other Src members Blk lacks cysteine residues in the SH4 domain that undergo palmitylation. Blk is required for the development of IL-17-producing gamma-delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. Blk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198234 [Multi-domain]  Cd Length: 100  Bit Score: 45.01  E-value: 1.02e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 441 EKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNCYAISFR----AEKKIKHCKIKL--EGRLYTTGTVQFESLVEL 514
Cdd:cd10371    3 EKWFFRTISRKDAERQLLAPMNKAGSFLIRESESNKGAFSLSVKdvttQGEVVKHYKIRSldNGGYYISPRITFPTLQAL 82

                         90
                 ....*....|....*...
gi 307167498 515 INYYERRPLYKKIKLSHP 532
Cdd:cd10371   83 VQHYSKKGDGLCQKLTLP 100
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
 329-418 1.12e-05

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 45.01  E-value: 1.12e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 329 GEKWFHGKLarGREEAEELLRHYSYlGDGTFLVRQCVTFVGDYCLSF--W---RKGKVNHCRIKlkqEMGQTQYYLIDTN 403
Cdd:cd10366    2 AEEWYFGKM--GRKDAERLLLNPGN-QRGIFLVRESETTKGAYSLSIrdWdevRGDNVKHYKIR---KLDNGGYYITTRA 75

                         90
                 ....*....|....*
gi 307167498 404 CFDSLYSLITHYRNH 418
Cdd:cd10366   76 QFDTLQKLVKHYTEH 90
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
 440-520 1.12e-05

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 44.96  E-value: 1.12e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAE-EMLKRIPTDGAFLVRPSERESNCYAISFR-----AEKKIKHCKIKL--EGRLYTTGTVQFESL 511
Cdd:cd10363    1 ETEEWFFKGISRKDAErQLLAPGNMLGSFMIRDSETTKGSYSLSVRdydpqHGDTVKHYKIRTldNGGFYISPRSTFSTL 80


                 ....*....
gi 307167498 512 VELINYYER 520
Cdd:cd10363   81 QELVDHYKK 89
SH3_CD2AP-like_3 cd11875
Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This ...
 562-610 1.13e-05

Third Src Homology 3 domain (SH3C) of CD2-associated protein and similar proteins; This subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212808 [Multi-domain]  Cd Length: 55  Bit Score: 43.49  E-value: 1.13e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 307167498 562 FTSKAKREDELTLVKHAIITNVN--VQRGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd11875    6 FDYEAENEDELTLREGDIVTILSkdCEDKGWWKGELNGKRG-VFPDNFVEP 55
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
 440-518 1.17e-05

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 44.90  E-value: 1.17e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAE-EMLKRIPTDGAFLVRPSERESNCYAISFR-----AEKKIKHCKI-KLE-GRLYTTGTVQFESL 511
Cdd:cd10367    1 QAEEWYFGKIGRKDAErQLLSPGNPRGAFLIRESETTKGAYSLSIRdwdqnRGDHVKHYKIrKLDtGGYYITTRAQFDTV 80


                 ....*..
gi 307167498 512 VELINYY 518
Cdd:cd10367   81 QELVQHY 87
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 439-519 1.49e-05

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 44.90  E-value: 1.49e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 439 HEEKEWWHPECTRIAAEEML-KRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKI---KLEGRLYTT---GTVQFESL 511
Cdd:cd10413    2 HRTQPWFHGRISREESQRLIgQQGLVDGVFLVRESQRNPQGFVLSLCHLQKVKHYLIlpsEEEGRLYFSmddGQTRFTDL 81


                 ....*...
gi 307167498 512 VELINYYE 519
Cdd:cd10413   82 LQLVEFHQ 89
SH3_Cortactin cd11959
Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src ...
 565-609 1.57e-05

Src homology 3 domain of Cortactin; Cortactin was originally identified as a substrate of Src kinase. It is an actin regulatory protein that binds to the Arp2/3 complex and stabilizes branched actin filaments. It is involved in cellular processes that affect cell motility, adhesion, migration, endocytosis, and invasion. It is expressed ubiquitously except in hematopoietic cells, where the homolog hematopoietic lineage cell-specific 1 (HS1) is expressed instead. Cortactin contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region interacts with the Arp2/3 complex and F-actin, and is crucial in regulating branched actin assembly. Cortactin also serves as a scaffold and provides a bridge to the actin cytoskeleton for membrane trafficking and signaling proteins that bind to its SH3 domain. Binding partners for the SH3 domain of cortactin include dynamin2, N-WASp, MIM, FGD1, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212892 [Multi-domain]  Cd Length: 53  Bit Score: 43.18  E-value: 1.57e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 307167498 565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVE 609
Cdd:cd11959    9 QAADDDEISFDPDDIITNIEMIDEGWWRGVCRGKYG-LFPANYVE 52
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
 440-532 1.95e-05

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 44.10  E-value: 1.95e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAE-EMLKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKL--EGRLYTTGTVQFESLVELIN 516
Cdd:cd10369    1 QAEPWFFGAIKRADAEkQLLYSENQTGAFLIRESESQKGEFSLSVLDGGVVKHYRIRRldEGGFFLTRRKTFSTLNEFVN 80

                         90
                 ....*....|....*.
gi 307167498 517 YYERRPLYKKIKLSHP 532
Cdd:cd10369   81 YYTTTSDGLCVKLGKP 96
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
 331-415 2.13e-05

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 44.40  E-value: 2.13e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 331 KWFHGKLARG--REEAEELLRHYSYLGdGTFLVRQCVTFVGDYCLSFWRKG-----KVNHCRIklkQEMGQTQYYLIDTN 403
Cdd:cd10344    7 KVYHGWLFEGlsREKAEELLMLPGNQV-GSFLIRESETRRGCYSLSVRHRGsqsrdSVKHYRI---FRLDNGWFYISPRL 82

                         90
                 ....*....|..
gi 307167498 404 CFDSLYSLITHY 415
Cdd:cd10344   83 TFQCLEDMVNHY 94
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 839-940 2.65e-05

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 44.58  E-value: 2.65e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 839 LYGVESLKICLKVIGARHL--MKSGrGTASPSIEVEII-GADfdSGTKLTTKTIPdNGFNPMWNETCEFEIFNPYFA--- 912
Cdd:cd04035    9 LYDPANSALHCTIIRAKGLkaMDAN-GLSDPYVKLNLLpGAS--KATKLRTKTVH-KTRNPEFNETLTYYGITEEDIqrk 84

                         90       100
                 ....*....|....*....|....*...
gi 307167498 913 LIRFLVQDEDMFGdSNFIGQATYPVRCL 940
Cdd:cd04035   85 TLRLLVLDEDRFG-NDFLGETRIPLKKL 111
SH3_AHI-1 cd11812
Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called ...
 565-608 2.88e-05

Src Homology 3 domain of Abelson helper integration site-1 (AHI-1); AHI-1, also called Jouberin, is expressed in high levels in the brain, gonad tissues, and skeletal muscle. It is an adaptor protein that interacts with the small GTPase Rab8a and regulates it distribution and function, affecting cilium formation and vesicle transport. Mutations in the AHI-1 gene can cause Joubert syndrome, a disorder characterized by brainstem malformations, cerebellar aplasia/hypoplasia, and retinal dystrophy. AHI-1 variation is also associated with susceptibility to schizophrenia and type 2 diabetes mellitus progression. AHI-1 contains WD40 and SH3 domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212746 [Multi-domain]  Cd Length: 52  Bit Score: 42.50  E-value: 2.88e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 307167498 565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYV 608
Cdd:cd11812    9 TANRSDELTIHRGDIIRVLYKDNDNWWFGSLVNGQQGYFPANYV 52
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
 330-415 3.05e-05

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 43.65  E-value: 3.05e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 330 EKWFHGKLARgrEEAEELLRHySYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGqtqYYLIDTNCFDSLY 409
Cdd:cd10370    3 EPWYFGKIKR--IEAEKKLLL-PENEHGAFLIRDSESRHNDYSLSVRDGDTVKHYRIRQLDEGG---FFIARRTTFRTLQ 76


                 ....*.
gi 307167498 410 SLITHY 415
Cdd:cd10370   77 ELVEHY 82
SH3_Intersectin_4 cd11839
Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor ...
 565-609 3.13e-05

Fourth Src homology 3 domain (or SH3D) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212773 [Multi-domain]  Cd Length: 58  Bit Score: 42.33  E-value: 3.13e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 307167498 565 KAKREDELTLVKHAIITNVNVQRGGWWRGDY---GGKKQ-HWFPANYVE 609
Cdd:cd11839    9 TATAENQLSLAVGQLVLVRKKSPSGWWEGELqarGKKRQiGWFPANYVK 57
SH3_MyoIe_If_like cd11827
Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If ...
 570-610 3.38e-05

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212761 [Multi-domain]  Cd Length: 53  Bit Score: 42.02  E-value: 3.38e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 307167498 570 DELTLVKHAIITNVNVQRGGWWRGDYGGkKQHWFPANYVEE 610
Cdd:cd11827   14 DELSFNEGDIIEILKEDPSGWWTGRLRG-KEGLFPGNYVEK 53
SH2_STAP1 cd10403
Src homology 2 domain found in Signal-transducing adaptor protein 1 (STAP1); STAP1 is a ...
 447-518 3.65e-05

Src homology 2 domain found in Signal-transducing adaptor protein 1 (STAP1); STAP1 is a signal-transducing adaptor protein. It is composed of a Pleckstrin homology (PH) and SH2 domains along with several tyrosine phosphorylation sites. STAP-1 is an ortholog of BRDG1 (BCR downstream signaling 1). STAP1 protein functions as a docking protein acting downstream of Tec tyrosine kinase in B cell antigen receptor signaling. The protein is phosphorylated by Tec and participates in a positive feedback loop, increasing Tec activity. STAP1 has been shown to interact with C19orf2, an unconventional prefoldin RPB5 interactor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198266  Cd Length: 94  Bit Score: 43.17  E-value: 3.65e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 447 PEC----TRIAAEEMLKRIPTDGAFLVRPSERESNcYAISFRAE---KKIKHCKIKLEGRLYTT---GTVQFESLVELIN 516
Cdd:cd10403    1 PACfykvSRKEAEELLERNPSCGNMLLRPGSDSSN-YSITTRQEinkPRIKHYRVMSRGQGYTIeleKPVTCPTLHDVIN 79


                 ..
gi 307167498 517 YY 518
Cdd:cd10403   80 YF 81
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
 444-523 3.73e-05

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198275  Cd Length: 97  Bit Score: 43.34  E-value: 3.73e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEM--LKRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRlyTTGTVQ---FESLVELINYY 518
Cdd:cd10412   10 WFHGPISRVKAAQLvqLQGPDAHGVFLVRQSETRRGEYVLTFNFQGRAKHLRLSLTER--GQCRVQhlhFPSVVDMLHHF 87


                 ....*
gi 307167498 519 ERRPL 523
Cdd:cd10412   88 QRSPI 92
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
 437-535 3.83e-05

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198260 [Multi-domain]  Cd Length: 106  Bit Score: 43.67  E-value: 3.83e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 437 NKHEEKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSERESNcYAISFRAEK------KIKHCKI--KLEGRLYTTGTVQF 508
Cdd:cd10397    1 DSLEMYEWYSKNMTRSQAEQLLKQEGKEGGFIVRDSSKAGK-YTVSVFAKSagdpqgVIRHYVVcsTPQSQYYLAEKHLF 79

                         90       100
                 ....*....|....*....|....*..
gi 307167498 509 ESLVELINYYERRPLYKKIKLSHPVNQ 535
Cdd:cd10397   80 STIPELINYHQHNAAGLISRLKYPVSS 106
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 846-940 4.06e-05

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 44.10  E-value: 4.06e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 846 KICLKVIGARHLM-KSGRGTASPSIEVEIigadfdSGTKLTTKTIPDNgFNPMWNETCEFEIFNPYfALIRFLVQDEDMF 924
Cdd:cd04027    2 KISITVVCAQGLIaKDKTGTSDPYVTVQV------GKTKKRTKTIPQN-LNPVWNEKFHFECHNSS-DRIKVRVWDEDDD 73

                         90       100
                 ....*....|....*....|....*..
gi 307167498 925 GDS-----------NFIGQATYPVRCL 940
Cdd:cd04027   74 IKSrlkqkftresdDFLGQTIIEVRTL 100
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
 445-515 4.07e-05

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 43.12  E-value: 4.07e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 307167498 445 WHPECTRIAAEEMLKRIPtDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEG--RLYTTGTVQFESLVELI 515
Cdd:cd10352    9 YHGLISREEAEQLLSGAS-DGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGknHYHYVGEKRFDTIHDLV 80
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
 332-420 4.40e-05

Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76); BLNK (also known as SLP-65 or BASH) is an important adaptor protein expressed in B-lineage cells. BLNK consists of a N-terminal sterile alpha motif (SAM) domain and a C-terminal SH2 domain. BLNK is a cytoplasmic protein, but a part of it is bound to the plasma membrane through an N-terminal leucine zipper motif and transiently bound to a cytoplasmic domain of Iga through its C-terminal SH2 domain upon B cell antigen receptor (BCR)-stimulation. A non-ITAM phosphotyrosine in Iga is necessary for the binding with the BLNK SH2 domain and/or for normal BLNK function in signaling and B cell activation. Upon phosphorylation BLNK binds Btk and PLCgamma2 through their SH2 domains and mediates PLCgamma2 activation by Btk. BLNK also binds other signaling molecules such as Vav, Grb2, Syk, and HPK1. BLNK has been shown to be necessary for BCR-mediated Ca2+ mobilization, for the activation of mitogen-activated protein kinases such as ERK, JNK, and p38 in a chicken B cell line DT40, and for activation of transcription factors such as NF-AT and NF-kappaB in human or mouse B cells. BLNK is involved in B cell development, B cell survival, activation, proliferation, and T-independent immune responses. BLNK is structurally homologous to SLP-76. SLP-76 and (linker for activation of T cells) LAT are adaptor/linker proteins in T cell antigen receptor activation and T cell development. BLNK interacts with many downstream signaling proteins that interact directly with both SLP-76 and LAT. New data suggest functional complementation of SLP-76 and LAT in T cell antigen receptor function with BLNK in BCR function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198183  Cd Length: 121  Bit Score: 43.84  E-value: 4.40e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARGreEAEELLRHYSylGDGTFLVRQCVTFVGD--YCLSFWRKGKVNHCRIKLKQEmgqTQYYLIDTNC----- 404
Cdd:cd09929   13 WYAGNIDRK--EAEEALRRSN--KDGTFLVRDSSGKDSSqpYTLMVLYNDKVYNIQIRFLEN---TRQYALGTGLrgeet 85

                         90
                 ....*....|....*.
gi 307167498 405 FDSLYSLITHYRNHPL 420
Cdd:cd09929   86 FSSVAEIIEHHQKTPL 101
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
 437-533 4.55e-05

Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member of the Tec protein tyrosine kinase Itk is expressed thymus, spleen, lymph node, T lymphocytes, NK and mast cells. It plays a role in T-cell proliferation and differentiation, analogous to Tec family kinases Txk. Itk has been shown to interact with Fyn, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2, and Peptidylprolyl isomerase A. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198259  Cd Length: 108  Bit Score: 43.63  E-value: 4.55e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 437 NKHEEKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSeRESNCYAISF------RAEKKIKHCKIK----LEGRLYTTGTV 506
Cdd:cd10396    1 NNLDQYEWYNKNINRSKAEKLLRDEGKEGGFMVRDS-SQPGLYTVSLytkaggEGNPCIRHYHIKetndSPKKYYLAEKH 79

                         90       100
                 ....*....|....*....|....*..
gi 307167498 507 QFESLVELINYYERRPLYKKIKLSHPV 533
Cdd:cd10396   80 VFNSIPELIEYHKHNAAGLVTRLRYPV 106
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
 330-415 5.28e-05

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 42.94  E-value: 5.28e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 330 EKWFHGKLARGREEAEELlrhYSYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGqtqYYLIDTNCFDSLY 409
Cdd:cd10369    3 EPWFFGAIKRADAEKQLL---YSENQTGAFLIRESESQKGEFSLSVLDGGVVKHYRIRRLDEGG---FFLTRRKTFSTLN 76


                 ....*.
gi 307167498 410 SLITHY 415
Cdd:cd10369   77 EFVNYY 82
SH2_Grb10 cd10415
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) ...
 439-532 5.30e-05

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb10 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198278  Cd Length: 108  Bit Score: 43.47  E-value: 5.30e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 439 HEEKEWWHPECTRIAAEEMLKRI-PTDGAFLVRPSERESNCYAISFRAEKKIKHCKI---KLEGRLYTT---GTVQFESL 511
Cdd:cd10415    2 HRTQHWFHGRISREESHRIIKQQgLVDGLFLLRDSQSNPKAFVLTLCHHQKIKNFQIlpcEDDGQTFFSlddGNTKFSDL 81

                         90       100
                 ....*....|....*....|.
gi 307167498 512 VELINYYERRPLYKKIKLSHP 532
Cdd:cd10415   82 IQLVDFYQLNKGVLPCKLKHH 102
SH3_Abp1_eu cd11960
Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like ...
 565-609 6.31e-05

Src homology 3 domain of eumetazoan Actin-binding protein 1; Abp1, also called drebrin-like protein, is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a helical domain, and a C-terminal SH3 domain. Mammalian Abp1, unlike yeast Abp1, does not contain an acidic domain that interacts with the Arp2/3 complex. It regulates actin dynamics indirectly by interacting with dynamin and WASP family proteins. Abp1 deficiency causes abnormal organ structure and function of the spleen, heart, and lung of mice. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212893 [Multi-domain]  Cd Length: 54  Bit Score: 41.62  E-value: 6.31e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 307167498 565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYVE 609
Cdd:cd11960    9 QAADDTEISFDPGDIITDIEQIDEGWWRGTGPDGTYGLFPANYVE 53
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
 444-519 6.61e-05

Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198214  Cd Length: 103  Bit Score: 42.95  E-value: 6.61e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 307167498 444 WWHPECTRIAAEEMLKRIPtDGAFLVRPSERESNcYAISFRAEKKIKHCKIKLEGRLYTTGTV---QFESLVELINYYE 519
Cdd:cd10351    9 WFHGIISREEAEALLMNAT-EGSFLVRVSEKIWG-YTLSYRLQSGFKHFLVDASGDFYSFLGVdpnRHATLTDLIDFHK 85
SH2_SHB cd10389
Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in ...
 444-533 7.44e-05

Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198252  Cd Length: 97  Bit Score: 42.77  E-value: 7.44e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLkRIPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTTG--TVQFESLVELINYYERR 521
Cdd:cd10389    3 WYHGAISRGDAENLL-RLCKECSYLVRNSQTSKHDYSLSLKSNQGFMHMKLAKTKEKYVLGqnSPPFDSVPEVIHYYTTR 81

                         90
                 ....*....|....*.
gi 307167498 522 PLYKK----IKLSHPV 533
Cdd:cd10389   82 KLPIKgaehLSLLYPV 97
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
 332-435 7.57e-05

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 42.81  E-value: 7.57e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARGReeAEELLRHYSYlgDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRI------KLKQEMGQTqyylIDTNCF 405
Cdd:cd10343    5 WYHGNITRSK--AEELLSKAGK--DGSFLVRDSESVSGAYALCVLYQNCVHTYRIlpnaedKLSVQASEG----VPVRFF 76

                         90       100       110
                 ....*....|....*....|....*....|
gi 307167498 406 DSLYSLITHYRNhplRSQEFLITLQEPVPQ 435
Cdd:cd10343   77 TTLPELIEFYQK---ENMGLVTHLLYPVER 103
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
 332-432 9.12e-05

Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav1 plays a role in T-cell and B-cell development and activation. It has been identified as the specific binding partner of Nef proteins from HIV-1, resulting in morphological changes, cytoskeletal rearrangements, and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Vav1 has been shown to interact with Ku70, PLCG1, Lymphocyte cytosolic protein 2, Janus kinase 2, SIAH2, S100B, Abl gene, ARHGDIB, SHB, PIK3R1, PRKCQ, Grb2, MAPK1, Syk, Linker of activated T cells, Cbl gene and EZH2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198268  Cd Length: 103  Bit Score: 42.69  E-value: 9.12e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHYSylgDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMgqtqYYLIDTNCFDSLYSL 411
Cdd:cd10405    7 WYAGPMER--AGAESILANRS---DGTYLVRQRVKDAAEFAISIKYNVEVKHIKIMTAEGL----YRITEKKAFRGLTEL 77

                         90       100
                 ....*....|....*....|...
gi 307167498 412 ITHYRNHPLRS--QEFLITLQEP 432
Cdd:cd10405   78 VEFYQQNSLKDcfKSLDTTLQFP 100
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 332-424 9.63e-05

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198272  Cd Length: 98  Bit Score: 42.33  E-value: 9.63e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHYSYLGDgtFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMgqtqyYLIDTNCFDSLYSL 411
Cdd:cd10409    3 WYYGNVTR--HQAECALNERGVEGD--FLIRDSESSPSDFSVSLKAVGKNKHFKVQLVDNV-----YCIGQRRFNSMDEL 73

                         90
                 ....*....|...
gi 307167498 412 ITHYRNHPLRSQE 424
Cdd:cd10409   74 VEHYKKAPIFTSE 86
SH3_VAV1_2 cd11976
C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly ...
 566-610 1.07e-04

C-terminal (or second) Src homology 3 domain of VAV1 protein; VAV1 is expressed predominantly in the hematopoietic system and it plays an important role in the development and activation of B and T cells. It is activated by tyrosine phosphorylation to function as a guanine nucleotide exchange factor (GEF) for Rho GTPases following cell surface receptor activation, triggering various effects such as cytoskeletal reorganization, transcription regulation, cell cycle progression, and calcium mobilization. It also serves as a scaffold protein and has been shown to interact with Ku70, Socs1, Janus kinase 2, SIAH2, S100B, Abl gene, ZAP-70, SLP76, and Syk, among others. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The C-terminal SH3 domain of Vav1 interacts with a wide variety of proteins including cytoskeletal regulators (zyxin), RNA-binding proteins (Sam68), transcriptional regulators, viral proteins, and dynamin 2. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212909 [Multi-domain]  Cd Length: 54  Bit Score: 40.70  E-value: 1.07e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 307167498 566 AKREDELTLVKHAIITNVNVQ-RGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd11976   10 ARDRSELSLKEGDIIKILNKKgQQGWWRGEIYGRVG-WFPANYVEE 54
SH3_Intersectin_1 cd11836
First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor ...
 566-609 1.07e-04

First Src homology 3 domain (or SH3A) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The first SH3 domain (or SH3A) of ITSN1 has been shown to bind many proteins including Sos1, dynamin1/2, CIN85, c-Cbl, PI3K-C2, SHIP2, N-WASP, and CdGAP, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212770 [Multi-domain]  Cd Length: 55  Bit Score: 40.80  E-value: 1.07e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 307167498 566 AKREDELTLVKHAIITNVNVQRG--GWWRGDYGGKkQHWFPANYVE 609
Cdd:cd11836   10 ARNPDEISFQPGDIIQVDESQVAepGWLAGELKGK-TGWFPANYVE 54
SH2_SHE cd10391
Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed ...
 444-533 1.07e-04

Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed in heart, lung, brain, and skeletal muscle. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198254  Cd Length: 98  Bit Score: 42.25  E-value: 1.07e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLKRIPtDGAFLVRPSERESNCYAISFRAEK--------KIKHCKIKLEgrlYTTGTvqFESLVELI 515
Cdd:cd10391    3 WYHGSISRAEAESRLQPCK-EASYLVRNSESGNSKYSIALKTSQgcvhiivaQTKDNKYTLN---QTSAV--FDSIPEVV 76

                         90       100
                 ....*....|....*....|..
gi 307167498 516 NYY--ERRPL--YKKIKLSHPV 533
Cdd:cd10391   77 HYYsnEKLPFkgAEHMTLLHPV 98
SH3_Abp1_fungi_C2 cd11961
Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
 566-610 1.22e-04

Second C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212894 [Multi-domain]  Cd Length: 53  Bit Score: 40.59  E-value: 1.22e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 307167498 566 AKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd11961   10 AAEDNELSFFENDKIINIEFVDDDWWLGECHGSRG-LFPSNYVEL 53
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 332-434 1.22e-04

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 42.22  E-value: 1.22e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLArgREEAEELLrhysYLG---DGTFLVRQcVTFVGDYCLSFWRKGKVNHCRIkLKQEMGqtQYYLIDTNCFDSL 408
Cdd:cd10402   12 WYHGSIA--RDEAERRL----YSGaqpDGKFLLRE-RKESGTYALSLVYGKTVYHYRI-DQDKSG--KYSIPEGTKFDTL 81

                         90       100
                 ....*....|....*....|....*.
gi 307167498 409 YSLITHYRnhpLRSQEFLITLQEPVP 434
Cdd:cd10402   82 WQLVEYLK---LKPDGLIFVLRESCP 104
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
 440-534 1.26e-04

Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine kinase Bmx is expressed in the endothelium of large arteries, fetal endocardium, adult endocardium of the left ventricle, bone marrow, lung, testis, granulocytes, myeloid cell lines, and prostate cell lines. Bmx is involved in the regulation of Rho and serum response factor (SRF). Bmx has been shown to interact with PAK1, PTK2, PTPN21, and RUFY1. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains. It is not present in Txk and the type 1 splice form of the Drosophila homolog. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198262  Cd Length: 106  Bit Score: 42.25  E-value: 1.26e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAEEMLKRIPTDGAFLVRPSErESNCYAIS----FRAEKK--IKHCKIKL--EGRLYTTGTVQFESL 511
Cdd:cd10399    4 DAYDWFAGNISRSQSEQLLRQKGKEGAFMVRNSS-QVGMYTVSlfskAVNDKKgtVKHYHVHTnaENKLYLAENYCFDSI 82

                         90       100
                 ....*....|....*....|...
gi 307167498 512 VELINYYERRPLYKKIKLSHPVN 534
Cdd:cd10399   83 PKLIHYHQHNSAGMITRLRHPVS 105
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
 444-518 1.35e-04

Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199830  Cd Length: 77  Bit Score: 41.35  E-value: 1.35e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 444 WWHPECTRIAAEEMLKRIPTdGAFLVRPSERESNcYAISFRAEKKIKHCKI-KLEGRLYTTG--TVQFESLVELINYY 518
Cdd:cd10349    2 WFHGFITRREAERLLEPKPQ-GCYLVRFSESAVT-FVLSYRSRTCCRHFLLaQLRDGRHVVLgeDSAHARLQDLLLHY 77
SH3_VAV_2 cd11830
C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as ...
 566-610 1.38e-04

C-terminal (or second) Src homology 3 domain of VAV proteins; VAV proteins function both as cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho GTPases and scaffold proteins and they play important roles in cell signaling by coupling cell surface receptors to various effector functions. They play key roles in processes that require cytoskeletal reorganization including immune synapse formation, phagocytosis, cell spreading, and platelet aggregation, among others. Vertebrates have three VAV proteins (VAV1, VAV2, and VAV3). VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212764 [Multi-domain]  Cd Length: 54  Bit Score: 40.69  E-value: 1.38e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 307167498 566 AKREDELTLVKHAIITNVN-VQRGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd11830   10 ARDMRELSLKEGDVVKIYNkKGQQGWWRGEINGRIG-WFPSTYVEE 54
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
 326-416 1.39e-04

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198277  Cd Length: 108  Bit Score: 42.22  E-value: 1.39e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 326 LHFGEKWFHGKLARgrEEAEELLRHYSyLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGQTQYYLIDTNC- 404
Cdd:cd10414    1 IHRSQPWFHHKISR--DEAQRLIIQQG-LVDGVFLVRDSQSNPRTFVLSMSHGQKIKHFQIIPVEDDGELFHTLDDGHTr 77

                         90
                 ....*....|..
gi 307167498 405 FDSLYSLITHYR 416
Cdd:cd10414   78 FTDLIQLVEFYQ 89
SH3_2 pfam07653
Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in ...
 568-611 1.55e-04

Variant SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.


Pssm-ID: 429575 [Multi-domain]  Cd Length: 54  Bit Score: 40.27  E-value: 1.55e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 307167498  568 REDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEEI 611
Cdd:pfam07653  12 DKNGLTLKKGDVVKVLGKDNDGWWEGETGGRVG-LVPSTAVEEI 54
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 444-522 1.73e-04

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 41.61  E-value: 1.73e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLKRI-PTDGAFLVRPSERESNCYAISFRAEKKIKHCKIK--LEGRLYTTGTVQFESLVELINYYER 520
Cdd:cd09938    3 FFYGSITREEAEEYLKLAgMSDGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIErqLNGTYAIAGGKAHCGPAELCEYHST 82


                 ..
gi 307167498 521 RP 522
Cdd:cd09938   83 DL 84
SH3_CD2AP-like_2 cd11874
Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This ...
 562-610 1.77e-04

Second Src Homology 3 domain (SH3B) of CD2-associated protein and similar proteins; This subfamily is composed of the second SH3 domain (SH3B) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3B of both proteins have been shown to bind to Cbl. In the case of CD2AP, its SH3B binds to Cbl at a site distinct from the c-Cbl/SH3A binding site. The CIN85 SH3B also binds ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212807 [Multi-domain]  Cd Length: 53  Bit Score: 40.01  E-value: 1.77e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRGGWWRGDYGGkKQHWFPANYVEE 610
Cdd:cd11874    6 FSYTPQNEDELELKVGDTIEVLGEVEEGWWEGKLNG-KVGVFPSNFVKE 53
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
 329-432 2.12e-04

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198270  Cd Length: 103  Bit Score: 41.53  E-value: 2.12e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 329 GEKWFHGKLARGREEAEELLRHYSylgdgTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMgqtqYYLIDTNCFDSL 408
Cdd:cd10407    4 CQPWYAGAMERLQAETELINRVNS-----TYLVRHRTKESGEYAISIKYNNEVKHIKILTRDGF----FHIAENRKFKSL 74

                         90       100
                 ....*....|....*....|....*.
gi 307167498 409 YSLITHYRNHPLRS--QEFLITLQEP 432
Cdd:cd10407   75 MELVEYYKHHSLKEgfRSLDTTLQFP 100
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 846-936 2.36e-04

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 42.22  E-value: 2.36e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 846 KICLKVIGARHL--MKSGrGTASPSIEVEIIGAD-FDSGTKLTTKTIPDNgFNPMWNETCEFEI----FNPYFALIRFLV 918
Cdd:cd04009   17 SLRVEILNARNLlpLDSN-GSSDPFVKVELLPRHlFPDVPTPKTQVKKKT-LFPLFDESFEFNVppeqCSVEGALLLFTV 94

                         90
                 ....*....|....*...
gi 307167498 919 QDEDMFGDSNFIGQATYP 936
Cdd:cd04009   95 KDYDLLGSNDFEGEAFLP 112
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
 331-428 2.62e-04

Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function as an adapter protein involved in tyrosine kinase signaling. It may also be involved in regulating cytokine signaling and cytoskeletal reorganization in hematopoietic cells. HSH2 contains several putative protein-binding motifs, SH3-binding proline-rich regions, and phosphotyrosine sites, but lacks enzymatic motifs. HSH2 was found to interact with cytokine-regulated tyrosine kinase c-FES and an activated Cdc42-associated tyrosine kinase ACK1. HSH2 binds c-FES through both its C-terminal region and its N-terminal region including the SH2 domain and binds ACK1 via its N-terminal proline-rich region. Both kinases bound and tyrosine-phosphorylated HSH2 in mammalian cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198199  Cd Length: 102  Bit Score: 41.03  E-value: 2.62e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 331 KWFHGKLArgREEAEELLRHYSYlgdGTFLVRQCVTFVGdYCLSFWRKGKVNHCRIKLKQEmgQTQYYLIDTNCFDSLYS 410
Cdd:cd09946    8 EWFHGAIS--REAAENMLESQPL---GSFLIRVSHSHVG-YTLSYKAQSSCRHFMVKLLDD--GTFMIPGEKVAHTSLHA 79

                         90
                 ....*....|....*...
gi 307167498 411 LITHYRNHPLRSQEFLIT 428
Cdd:cd09946   80 LVTFHQQKPIEPRRELLT 97
SH2_SOCS1 cd10382
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 454-532 2.76e-04

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198245  Cd Length: 98  Bit Score: 40.81  E-value: 2.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 454 AEEMLKRIPTdGAFLVRPSeRESNC-YAISFRAEKKIKHCKIKL-EGRLYTTGTVQ-FESLVELINYYERRPlykKIKLS 530
Cdd:cd10382   22 AHAKLKREPV-GTFLIRDS-RQKNCfFALSVKMASGPVSIRILFkAGKFSLDGSKEsFDCLFKLLEHYVASP---KKMLG 96


                 ..
gi 307167498 531 HP 532
Cdd:cd10382   97 RP 98
SH2_SOCS7 cd10388
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 453-515 2.80e-04

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198251  Cd Length: 101  Bit Score: 41.19  E-value: 2.80e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 453 AAEEMLKRIPtDGAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRLYTTGT-----VQFESLVELI 515
Cdd:cd10388   21 DAEKVLSNKP-DGSFLVRDSSDDRYIFSLSFRSQGSVHHTRIEQYQGTFSLGSrnkfvDRSQSLVEFI 87
PLN03008 PLN03008
Phospholipase D delta
 830-945 3.34e-04

Phospholipase D delta


Pssm-ID: 178585 [Multi-domain]  Cd Length: 868  Bit Score: 44.70  E-value: 3.34e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 830 DFNPYDKNTlYGVESLKICLKVIgarhlmksgrgTASPSIEVEIIGAdfdsgtKLTTKTIPDNGFNPMWNETCEFEIFNP 909
Cdd:PLN03008  54 DVDPRDKGE-FGDKNIRSHRKVI-----------TSDPYVTVVVPQA------TLARTRVLKNSQEPLWDEKFNISIAHP 115

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 307167498 910 yFALIRFLVQDEDMFGdSNFIGQATYPVRCLRTGYR 945
Cdd:PLN03008 116 -FAYLEFQVKDDDVFG-AQIIGTAKIPVRDIASGER 149
SH3_Intersectin_2 cd11837
Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor ...
 559-610 3.74e-04

Second Src homology 3 domain (or SH3B) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The second SH3 domain (or SH3B) of ITSN1 has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212771 [Multi-domain]  Cd Length: 53  Bit Score: 39.27  E-value: 3.74e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 307167498 559 PTSFTSKAKREDELTLVKHAIITnVNVQRGGWWRGDYGGKKQHWFPANYVEE 610
Cdd:cd11837    3 TALYPWRAKKENHLSFAKGDIIT-VLEQQEMWWFGELEGGEEGWFPKSYVKE 53
SH3_9 pfam14604
Variant SH3 domain;
565-609 4.26e-04

Variant SH3 domain;


Pssm-ID: 434066 [Multi-domain]  Cd Length: 49  Bit Score: 38.75  E-value: 4.26e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 307167498  565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVE 609
Cdd:pfam14604   6 EPKDDDELSLQRGDVITVIEESEDGWWEGINTGRTG-LVPANYVE 49
SH3_VAV3_2 cd11978
C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed ...
 562-610 4.37e-04

C-terminal (or second) Src homology 3 domain of VAV3 protein; VAV3 is ubiquitously expressed and functions as a phosphorylation-dependent guanine nucleotide exchange factor (GEF) for RhoA, RhoG, and Rac1. It has been implicated to function in the hematopoietic, bone, cerebellar, and cardiovascular systems. VAV3 is essential in axon guidance in neurons that control blood pressure and respiration. It is overexpressed in prostate cancer cells and it plays a role in regulating androgen receptor transcriptional activity. VAV proteins contain several domains that enable their function: N-terminal calponin homology (CH), acidic, RhoGEF (also called Dbl-homologous or DH), Pleckstrin Homology (PH), C1 (zinc finger), SH2, and two SH3 domains. The SH3 domain of VAV is involved in the localization of proteins to specific sites within the cell, by interacting with proline-rich sequences within target proteins. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212911 [Multi-domain]  Cd Length: 56  Bit Score: 39.24  E-value: 4.37e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 307167498 562 FTSKAKREdeLTLVKHAIIT-NVNVQRGGWWRGDYGGKKQhWFPANYVEE 610
Cdd:cd11978    9 FCARDMRE--LSLLKGDVVKiYTKMSTNGWWRGEVNGRVG-WFPSTYVEE 55
SH3_D21-like cd12142
Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; ...
 562-609 4.56e-04

Src Homology 3 domain of SH3 domain-containing protein 21 (SH3D21) and similar proteins; N-terminal SH3 domain of the uncharacterized protein SH3 domain-containing protein 21, and similar uncharacterized domains, it belongs to the CD2AP-like_3 subfamily of proteins. The CD2AP-like_3 subfamily is composed of the third SH3 domain (SH3C) of CD2AP, CIN85 (Cbl-interacting protein of 85 kDa), and similar domains. CD2AP and CIN85 are adaptor proteins that bind to protein partners and assemble complexes that have been implicated in T cell activation, kidney function, and apoptosis of neuronal cells. They also associate with endocytic proteins, actin cytoskeleton components, and other adaptor proteins involved in receptor tyrosine kinase (RTK) signaling. CD2AP and the main isoform of CIN85 contain three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP and CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. SH3C of both proteins have been shown to bind to ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213018 [Multi-domain]  Cd Length: 55  Bit Score: 38.99  E-value: 4.56e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQRG--GWWRGDYGGKKQhWFPANYVE 609
Cdd:cd12142    6 FDYNPVAPDELALKKGDVIEVISKETEdeGWWEGELNGRRG-FFPDNFVM 54
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
 442-521 4.78e-04

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 40.43  E-value: 4.78e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 442 KEWWHPECTRIAAE-EMLKRIPTDGAFLVRPSERESNCYAISFR-----AEKKIKHCKI-KLE-GRLYTTGTVQFESLVE 513
Cdd:cd10419    3 EEWYFGKLGRKDAErQLLSFGNPRGTFLIRESETTKGAYSLSIRdwddmKGDHVKHYKIrKLDnGGYYITTRAQFETLQQ 82


                 ....*...
gi 307167498 514 LINYYERR 521
Cdd:cd10419   83 LVQHYSEK 90
SH3_CIN85_3 cd12057
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called ...
 562-609 4.91e-04

Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa; CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212990 [Multi-domain]  Cd Length: 56  Bit Score: 39.11  E-value: 4.91e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 307167498 562 FTSKAKREDELTLVKHAIITNVNVQ--RGGWWRGDYGGkKQHWFPANYVE 609
Cdd:cd12057    6 FPYEAQNEDELTIKEGDIVTLISKDciDAGWWEGELNG-RRGVFPDNFVK 54
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 860-952 5.05e-04

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 40.66  E-value: 5.05e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 860 SGRGTASPSieVEIIgadFDSGTKLTTKTIPDNGfNPMWNETCEFEIFNPYFALIRFLVQDEDMFGDsNFIGQATYP--- 936
Cdd:cd04052    8 SKTGLLSPY--AELY---LNGKLVYTTRVKKKTN-NPSWNASTEFLVTDRRKSRVTVVVKDDRDRHD-PVLGSVSISlnd 80

                         90
                 ....*....|....*..
gi 307167498 937 -VRCLRTGYRSVPLKNV 952
Cdd:cd04052   81 lIDATSVGQQWFPLSGN 97
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 885-934 5.11e-04

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 41.09  E-value: 5.11e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 307167498 885 TTKTIPDNgFNPMWNETCEFEIFNPYFALIRFLVQDEDMFGDSNFIGQAT 934
Cdd:cd04043   39 KTRTIYDT-LNPRWDEEFELEVPAGEPLWISATVWDRSFVGKHDLCGRAS 87
SH3_Intersectin1_4 cd11993
Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor ...
 566-609 5.31e-04

Fourth Src homology 3 domain (or SH3D) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fourth SH3 domain (or SH3D) of ITSN1 has been shown to bind SHIP2, Numb, CdGAP, and N-WASP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212926  Cd Length: 65  Bit Score: 39.33  E-value: 5.31e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 307167498 566 AKREDELTLVKHAIITNVNVQRGGWWRGDYG--GKKQH--WFPANYVE 609
Cdd:cd11993   14 ATGPEQLTLAPGQLILIRKKNPGGWWEGELQarGKKRQigWFPANYVK 61
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
 441-515 5.53e-04

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkA and shkC. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198219  Cd Length: 113  Bit Score: 40.67  E-value: 5.53e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 307167498 441 EKEWWHPECTRIAAEEMLKRIPtDGAFLVRPSERESNCYAIS-FRAEKKIKHCKIKLEGRLYTTGTVQFESLVELI 515
Cdd:cd10356    9 ECAWFHGDISTSESENRLNGKP-EGTFLVRFSTSEPGAYTISkVSKNGGISHQRIHRPGGKFQVNNSKYLSVKELI 83
SH3_Tks4_2 cd12076
Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also ...
 566-610 5.84e-04

Second Src homology 3 domain of Tyrosine kinase substrate with four SH3 domains; Tks4, also called SH3 and PX domain-containing protein 2B (SH3PXD2B) or HOFI, is a Src substrate and scaffolding protein that plays an important role in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. It is required in the formation of functional podosomes, EGF-induced membrane ruffling, and lamellipodia generation. It plays an important role in cellular attachment and cell spreading. Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. It contains an N-terminal Phox homology (PX) domain and four SH3 domains. This model characterizes the second SH3 domain of Tks4. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213009 [Multi-domain]  Cd Length: 54  Bit Score: 38.86  E-value: 5.84e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 307167498 566 AKREDELTLVKHAIITNVNVQRGGWWRGDYGGkKQHWFPANYVEE 610
Cdd:cd12076   11 ARDQDEINLEKGAVVEVIQKNLEGWWKIRYQG-KEGWAPASYLKK 54
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
 332-432 6.21e-04

Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198269  Cd Length: 103  Bit Score: 40.05  E-value: 6.21e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 332 WFHGKLARgrEEAEELLRHYSylgDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMgqtqYYLIDTNCFDSLYSL 411
Cdd:cd10406    7 WFAGNMER--QQTDNLLKSHA---SGTYLIRERPAEAERFAISIKFNDEVKHIKVVEKDNW----IHITEAKKFESLLEL 77

                         90       100
                 ....*....|....*....|...
gi 307167498 412 ITHYRNHPLRS--QEFLITLQEP 432
Cdd:cd10406   78 VEYYQCHSLKEsfKQLDTTLKYP 100
SH3_Myosin-I_fungi cd11858
Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent ...
 571-610 6.28e-04

Src homology 3 domain of Type I fungal Myosins; Type I myosins (myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Saccharomyces cerevisiae has two myosins-I, Myo3 and Myo5, which are involved in endocytosis and the polarization of the actin cytoskeleton. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212792 [Multi-domain]  Cd Length: 55  Bit Score: 38.52  E-value: 6.28e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 307167498 571 ELTLVKHAIITNVNVQRGGWWRG-DYGGKKQHWFPANYVEE 610
Cdd:cd11858   15 ELSLKKDDIVYIVQKEDNGWWLAkKLDESKEGWVPAAYLEE 55
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 846-932 7.45e-04

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 40.64  E-value: 7.45e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 846 KICLKVIGARHLMKS-GRGTASPSIEVEIIGADFDSGTKlTTKTIPDNgFNPMWNETCEFEIfnPYFAL----IRFLVQD 920
Cdd:cd00276   15 RLTVVVLKARNLPPSdGKGLSDPYVKVSLLQGGKKLKKK-KTSVKKGT-LNPVFNEAFSFDV--PAEQLeevsLVITVVD 90

                         90
                 ....*....|..
gi 307167498 921 EDMFGDSNFIGQ 932
Cdd:cd00276   91 KDSVGRNEVIGQ 102
SH3_CD2AP_1 cd12053
First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ...
 566-611 7.58e-04

First Src Homology 3 domain (SH3A) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the first SH3 domain (SH3A) of CD2AP. SH3A binds to the PXXXPR motif present in c-Cbl and the cytoplasmic domain of cell adhesion protein CD2. Its interaction with CD2 anchors CD2 at sites of cell contact. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212986  Cd Length: 56  Bit Score: 38.67  E-value: 7.58e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 307167498 566 AKREDELTLVKHAIITNVN-VQRGGWWRGDYGGKKQhWFPANYVEEI 611
Cdd:cd12053   10 AVHEDELTIRVGEIIRNVKkLEEEGWLEGELNGRRG-MFPDNFVKEI 55
SH3_Abi cd11826
Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor ...
 566-609 8.94e-04

Src homology 3 domain of Abl Interactor proteins; Abl interactor (Abi) proteins are adaptor proteins serving as binding partners and substrates of Abl tyrosine kinases. They are involved in regulating actin cytoskeletal reorganization and play important roles in membrane-ruffling, endocytosis, cell motility, and cell migration. They localize to sites of actin polymerization in epithelial adherens junction and immune synapses, as well as to the leading edge of lamellipodia. Vertebrates contain two Abi proteins, Abi1 and Abi2. Abi1 displays a wide expression pattern while Abi2 is highly expressed in the eye and brain. Abi proteins contain a homeobox homology domain, a proline-rich region, and a SH3 domain. The SH3 domain of Abi binds to a PxxP motif in Abl. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212760 [Multi-domain]  Cd Length: 52  Bit Score: 38.07  E-value: 8.94e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 307167498 566 AKREDELTLVKHAIITNVNVQRGGWWRGDYGGkKQHWFPANYVE 609
Cdd:cd11826   10 ADKDDELSFQEGDIIYVTKKNDDGWYEGVLNG-VTGLFPGNYVE 52
SH2_SHD cd10390
Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression ...
 330-423 1.10e-03

Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression of SHD is restricted to the brain. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198253  Cd Length: 98  Bit Score: 39.30  E-value: 1.10e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 330 EKWFHGKLARGreEAEELLrhySYLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQE----MGQtqyyliDTNCF 405
Cdd:cd10390    1 QPWFHGPLSRA--DAENLL---SLCKEGSYLVRLSETRPQDCSLSLRSSQGFLHLKFARTREnqvvLGQ------HSGPF 69

                         90
                 ....*....|....*...
gi 307167498 406 DSLYSLITHYRNHPLRSQ 423
Cdd:cd10390   70 PSVPELVLHYSSRPLPVQ 87
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 849-959 1.27e-03

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members of this cd have a type-II topology.


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 39.55  E-value: 1.27e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 849 LKVIGARHLMKSGR-GTASPSIEVEIIGAdfdSGTKLTTKTIpDNGFNPMWNETCEFEIFNPYFALIRFLVQDEDMFGDS 927
Cdd:cd04036    4 VRVLRATNITKGDLlSTPDCYVELWLPTA---SDEKKRTKTI-KNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMDD 79

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 307167498 928 NfIGQATYPVRCLRTGYR---SVPLKNVYSEDLEL 959
Cdd:cd04036   80 H-LGTVLFDVSKLKLGEKvrvTFSLNPQGKEELEV 113
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 850-951 1.30e-03

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 39.59  E-value: 1.30e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 850 KVIGARHLMKSGRGTAS-PSIEVEIIGAdfdsgtKLTTKTIPDNgFNPMWNETCEFEIFNpYFALIRFLVQDEDMFGDSN 928
Cdd:cd08377    6 KVIRASGLAAADIGGKSdPFCVLELVNA------RLQTHTIYKT-LNPEWNKIFTFPIKD-IHDVLEVTVYDEDKDKKPE 77

                         90       100
                 ....*....|....*....|....
gi 307167498 929 FIGQATYPVRCLRTGYRSV-PLKN 951
Cdd:cd08377   78 FLGKVAIPLLSIKNGERKWyALKD 101
SH3_Intersectin2_2 cd11990
Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor ...
 566-609 1.36e-03

Second Src homology 3 domain (or SH3B) of Intersectin-2; Intersectin-2 (ITSN2) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN2 also functions as a specific GEF for Cdc42 activation in epithelial morphogenesis, and is required in mitotic spindle orientation. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The second SH3 domain (or SH3B) of ITSN2 is expected to bind protein partners, similar to ITSN1 which has been shown to bind WNK and CdGAP. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212923 [Multi-domain]  Cd Length: 52  Bit Score: 37.71  E-value: 1.36e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 307167498 566 AKREDELTLVKHAIITnVNVQRGGWWRGDYGGkKQHWFPANYVE 609
Cdd:cd11990   10 AKKDNHLNFSKNDIIT-VLEQQENWWFGEVHG-GRGWFPKSYVK 51
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 886-945 1.67e-03

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175982 [Multi-domain]  Cd Length: 158  Bit Score: 39.98  E-value: 1.67e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 307167498 886 TKTIPDNGfNPMWNETceFEIF-NPYFALIRFLVQDEDMFGdSNFIGQATYPVRCLRTGYR 945
Cdd:cd04015   74 TRVIENSE-NPVWNES--FHIYcAHYASHVEFTVKDNDVVG-AQLIGRAYIPVEDLLSGEP 130
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 883-933 1.75e-03

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 40.00  E-value: 1.75e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 307167498 883 KLTTKTIPDNgFNPMWNETCEFEIFNPYfALIRFLVQDEDMFGDSNFIGQA 933
Cdd:cd04038   34 KVKTRVIKKN-LNPVWNEELTLSVPNPM-APLKLEVFDKDTFSKDDSMGEA 82
SH2_C-SH2_Zap70_Syk_like cd10345
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 444-517 2.13e-03

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198208  Cd Length: 95  Bit Score: 38.51  E-value: 2.13e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 307167498 444 WWHPECTRIAAEEML-KRIPTDGAFLVRPsERESNCYAISFRAEKKIKHCKIKLE--GRLYTTGTVQFESLVELINY 517
Cdd:cd10345    2 WFHGKISREESEQIVlIGSKTNGKFLIRA-RDNNGSYALCLLHEGKVLHYRIDKDktGKLSIPEGKKFDTLWQLVEH 77
SH2_Grb10 cd10415
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) ...
 326-416 2.20e-03

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb10 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198278  Cd Length: 108  Bit Score: 38.85  E-value: 2.20e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 326 LHFGEKWFHGKLARgrEEAEELLRHYSYLgDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGQTQYYLIDTNC- 404
Cdd:cd10415    1 IHRTQHWFHGRISR--EESHRIIKQQGLV-DGLFLLRDSQSNPKAFVLTLCHHQKIKNFQILPCEDDGQTFFSLDDGNTk 77

                         90
                 ....*....|..
gi 307167498 405 FDSLYSLITHYR 416
Cdd:cd10415   78 FSDLIQLVDFYQ 89
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
 892-956 2.22e-03

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 39.27  E-value: 2.22e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 307167498 892 NGFNPMWNETCEFEIfNPYFALIRFLVQDEDMFGDSNFIGQATYPVRCLR---TGYRSVPLKNVYSED 956
Cdd:cd08678   40 NTSNPFWDEHFLFEL-SPNSKELLFEVYDNGKKSDSKFLGLAIVPFDELRknpSGRQIFPLQGRPYEG 106
SH3_GAS7 cd11829
Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the ...
 579-608 2.24e-03

Src homology 3 domain of Growth Arrest Specific protein 7; GAS7 is mainly expressed in the brain and is required for neurite outgrowth. It may also play a role in the protection and migration of embryonic stem cells. Treatment-related acute myeloid leukemia (AML) has been reported resulting from mixed-lineage leukemia (MLL)-GAS7 translocations as a complication of primary cancer treatment. GAS7 contains an N-terminal SH3 domain, followed by a WW domain, and a central F-BAR domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212763 [Multi-domain]  Cd Length: 52  Bit Score: 37.11  E-value: 2.24e-03
                         10        20        30
                 ....*....|....*....|....*....|
gi 307167498 579 IITNVNVQRGGWWRGDYGGKKQhWFPANYV 608
Cdd:cd11829   24 LIRVLQAPDGGWWEGEKDGLRG-WFPASYV 52
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 891-937 2.27e-03

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 38.85  E-value: 2.27e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 307167498 891 DNGFNPMWNETCEFEIFNPYFAL---IRFLVQDEDMFGDSNFIGQATYPV 937
Cdd:cd04049   42 GDGRNPEWNEKFKFTVEYPGWGGdtkLILRIMDKDNFSDDDFIGEATIHL 91
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 326-401 2.31e-03

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 38.74  E-value: 2.31e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 307167498 326 LHFGEKWFHGKLARgrEEAEELLRHYSyLGDGTFLVRQCVTFVGDYCLSFWRKGKVNHCRIKLKQEMGQTQYYLID 401
Cdd:cd10413    1 IHRTQPWFHGRISR--EESQRLIGQQG-LVDGVFLVRESQRNPQGFVLSLCHLQKVKHYLILPSEEEGRLYFSMDD 73
SH2_SH2B_family cd10346
Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein ...
 444-523 2.41e-03

Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein family has 3 members: SH2B1 (SH2-B, PSM), SH2B2 (APS), and SH2B3 (Lnk). SH2B family members contain a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198209  Cd Length: 97  Bit Score: 38.17  E-value: 2.41e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 444 WWHPECTRIAAEEMLKRIPTD--GAFLVRPSERESNCYAISFRAEKKIKHCKIKLEGRlyttGT--VQ---FESLVELIN 516
Cdd:cd10346   10 WFHGTLSRSDAAQLVLHSGADghGVFLVRQSETRRGEFVLTFNFQGRAKHLRLTLNEK----GQcrVQhlwFPSIFDMLE 85


                 ....*..
gi 307167498 517 YYERRPL 523
Cdd:cd10346   86 HFRQNPI 92
SH3_HS1 cd12073
Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 ...
 565-609 2.45e-03

Src homology 3 domain of Hematopoietic lineage cell-specific protein 1; HS1, also called HCLS1 (hematopoietic cell-specific Lyn substrate 1), is a cortactin homolog expressed specifically in hematopoietic cells. It is an actin regulatory protein that binds the Arp2/3 complex and stabilizes branched actin filaments. It is required for cell spreading and signaling in lymphocytes. It regulates cytoskeletal remodeling that controls lymphocyte trafficking, and it also affects tissue invasion and infiltration of leukemic B cells. Like cortactin, HS1 contains an N-terminal acidic domain, several copies of a repeat domain found in cortactin and HS1, a proline-rich region, and a C-terminal SH3 domain. The N-terminal region binds the Arp2/3 complex and F-actin, while the C-terminal region acts as an adaptor or scaffold that can connect varied proteins that bind the SH3 domain within the actin network. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 213006 [Multi-domain]  Cd Length: 55  Bit Score: 37.12  E-value: 2.45e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 307167498 565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVE 609
Cdd:cd12073   10 QGEGDDEISFDPQETITDIEMVDEGWWKGTCHGHRG-LFPANYVE 53
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
 440-518 2.57e-03

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 38.46  E-value: 2.57e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 440 EEKEWWHPECTRIAAEEMLkRIPTD--GAFLVRPSERESNCYAISFRAEKKI-----KHCKIKL--EGRLYTTGTVQFES 510
Cdd:cd10366    1 QAEEWYFGKMGRKDAERLL-LNPGNqrGIFLVRESETTKGAYSLSIRDWDEVrgdnvKHYKIRKldNGGYYITTRAQFDT 79


                 ....*...
gi 307167498 511 LVELINYY 518
Cdd:cd10366   80 LQKLVKHY 87
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 840-936 2.78e-03

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 38.85  E-value: 2.78e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 840 YGVESLKICLKVIGARHL-MKSGRGTASPSIEVEIIGadfDSGTKLTTKTIPDNgFNPMWNETCEFEIFnPYFALI-RFL 917
Cdd:cd08386   11 YDFQESTLTLKILKAVELpAKDFSGTSDPFVKIYLLP---DKKHKLETKVKRKN-LNPHWNETFLFEGF-PYEKLQqRVL 85

                         90       100
                 ....*....|....*....|..
gi 307167498 918 ---VQDEDMFGDSNFIGQATYP 936
Cdd:cd08386   86 ylqVLDYDRFSRNDPIGEVSLP 107
SH3_GRAF-like cd11882
Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar ...
 560-609 3.00e-03

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase and similar proteins; This subfamily is composed of Rho GTPase activating proteins (GAPs) with similarity to GRAF. Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. Although vertebrates harbor four Rho GAPs in the GRAF subfamily including GRAF, GRAF2, GRAF3, and Oligophrenin-1 (OPHN1), only three are included in this model. OPHN1 contains the BAR, PH and GAP domains, but not the C-terminal SH3 domain. GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. GRAF influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase. GRAF2 regulates caspase-activated p21-activated protein kinase-2. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.


Pssm-ID: 212815 [Multi-domain]  Cd Length: 54  Bit Score: 36.89  E-value: 3.00e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 307167498 560 TSFTSKAKREDELTLVKHAIITNVNVQR-GGWWRGDYGGKKQhWFPANYVE 609
Cdd:cd11882    4 ALYACKAEDESELSFEPGQIITNVQPSDePGWLEGTLNGRTG-LIPENYVE 53
SH3_Abp1_fungi_C1 cd11962
First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor ...
 569-609 3.33e-03

First C-terminal Src homology 3 domain of Fungal Actin-binding protein 1; Abp1 is an adaptor protein that functions in receptor-mediated endocytosis and vesicle trafficking. It contains an N-terminal actin-binding module, the actin-depolymerizing factor (ADF) homology domain, a central proline-rich region, and a C-terminal SH3 domain (many yeast Abp1 proteins contain two C-terminal SH3 domains). Yeast Abp1 also contains two acidic domains that bind directly to the Arp2/3 complex, which is required to initiate actin polymerization. The SH3 domain of yeast Abp1 binds and localizes the kinases, Ark1p and Prk1p, which facilitate actin patch disassembly following vesicle internalization. It also mediates the localization to the actin patch of the synaptojanin-like protein, Sjl2p, which plays a key role in endocytosis. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212895 [Multi-domain]  Cd Length: 54  Bit Score: 36.70  E-value: 3.33e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 307167498 569 EDELTLVKHAIITNVNVQRGGWWRGDYGGKKQHWFPANYVE 609
Cdd:cd11962   13 DNEIELVEGEIVTNIEMVDEDWWMGTNSKGESGLFPSNYVE 53
SH3_CD2AP_2 cd12054
Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ...
 567-611 4.07e-03

Second Src Homology 3 domain (SH3B) of CD2-associated protein; CD2AP, also called CMS (Cas ligand with Multiple SH3 domains) or METS1 (Mesenchyme-to-Epithelium Transition protein with SH3 domains), is a cytosolic adaptor protein that plays a role in regulating the cytoskeleton. It is critical in cell-to-cell union necessary for kidney function. It also stabilizes the contact between a T cell and antigen-presenting cells. It is primarily expressed in podocytes at the cytoplasmic face of the slit diaphragm and serves as a linker anchoring podocin and nephrin to the actin cytoskeleton. CD2AP contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CD2AP to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the second SH3 domain (SH3B) of CD2AP. SH3B binds to c-Cbl in a site (TPSSRPLR is the core binding motif) distinct from the c-Cbl/SH3A binding site. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212987 [Multi-domain]  Cd Length: 55  Bit Score: 36.48  E-value: 4.07e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 307167498 567 KREDELTLVKHAIITNVNVQRGGWWRGDYGGKKQhWFPANYVEEI 611
Cdd:cd12054   12 QNEDELELKVGDIIDINEEVEEGWWSGTLNGKSG-LFPSNFVKEL 55
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
 266-294 4.72e-03

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270094  Cd Length: 104  Bit Score: 37.70  E-value: 4.72e-03
                         10        20
                 ....*....|....*....|....*....
gi 307167498 266 KNGILYLEDPIDKEWNPHFFVLTQQKLFY 294
Cdd:cd13275    1 KKGWLMKQGSRQGEWSKHWFVLRGAALKY 29
SH3_p47phox_like cd11856
Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This ...
 565-610 7.47e-03

Src homology 3 domains of the p47phox subunit of NADPH oxidase and similar domains; This family is composed of the tandem SH3 domains of p47phox subunit of NADPH oxidase and Nox Organizing protein 1 (NoxO1), the four SH3 domains of Tks4 (Tyr kinase substrate with four SH3 domains), the five SH3 domains of Tks5, the SH3 domain of obscurin, Myosin-I, and similar domains. Most members of this group also contain Phox homology (PX) domains, except for obscurin and Myosin-I. p47phox and NoxO1 are regulators of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) and nonphagocytic NADPH oxidase Nox1, respectively. They play roles in the activation of their respective NADPH oxidase, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Tks proteins are Src substrates and scaffolding proteins that play important roles in the formation of podosomes and invadopodia, the dynamic actin-rich structures that are related to cell migration and cancer cell invasion. Obscurin is a giant muscle protein that plays important roles in the organization and assembly of the myofibril and the sarcoplasmic reticulum. Type I myosins (Myosin-I) are actin-dependent motors in endocytic actin structures and actin patches. They play roles in membrane traffic in endocytic and secretory pathways, cell motility, and mechanosensing. Myosin-I contains an N-terminal actin-activated ATPase, a phospholipid-binding TH1 (tail homology 1) domain, and a C-terminal extension which includes an F-actin-binding TH2 domain, an SH3 domain, and an acidic peptide that participates in activating the Arp2/3complex. The SH3 domain of myosin-I is required for myosin-I-induced actin polymerization. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.


Pssm-ID: 212790 [Multi-domain]  Cd Length: 53  Bit Score: 35.69  E-value: 7.47e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 307167498 565 KAKREDELTLVKHAIITNVNVQRGGWWRGDYGGkKQHWFPANYVEE 610
Cdd:cd11856    9 EAQGDDEISLQEGEVVEVLEKNDSGWWYVRKGD-KEGWVPASYLEP 53
SH2_SH2B1 cd10410
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, ...
 441-523 9.41e-03

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, PSM), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198273  Cd Length: 97  Bit Score: 36.53  E-value: 9.41e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 307167498 441 EKEWWHPECTRIAAEEMLKR--IPTDGAFLVRPSERESNCYAISFRAEKKIKHCKIKL--EGRLYTTgTVQFESLVELIN 516
Cdd:cd10410    7 GYPWFHGMLSRLKAAQLVLEggTGSHGVFLVRQSETRRGEYVLTFNFQGKAKHLRLSLneEGQCRVQ-HLWFQSIFDMLE 85


                 ....*..
gi 307167498 517 YYERRPL 523
Cdd:cd10410   86 HFRVHPI 92
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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