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Conserved domains on  [gi|1039751490|ref|XP_017172570|]
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kalirin isoform X43 [Mus musculus]

Protein Classification

RhoGEF family protein( domain architecture ID 11072364)

RhoGEF (rho guanine nucleotide exchange factor) family protein similar to Homo sapiens Rho guanine nucleotide exchange factor 25 (ARHGEF25) that may play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
378-512 1.80e-73

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270061  Cd Length: 140  Bit Score: 232.92  E-value: 1.80e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 378 LGRLQGFEGTLTAQGKLLQQDTFYVIELDAGMQSRTKERRVFLFEQIVIFSELLRKGS--LTPGYMFKRSIKMNYLVLED 455
Cdd:cd13241     1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAGLLQKGKERRVFLFEQIIIFSEILGKKTqfSNPGYIYKNHIKVNKMSLEE 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 456 NVDGDPCKFALMNRE---TSERVILQAANSDIQQAWVQDINQVLETQRDFLNALQSPIEY 512
Cdd:cd13241    81 NVDGDPLRFALKSRDpnnPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
204-373 3.35e-51

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


:

Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 175.18  E-value: 3.35e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 204 VLNELVQTEKDYVKDLGIVVEGFMKRIEE--KGVPEDMrgkeKIVFGNIHQIYDWHKDFFLAELEKCIQEQDRLAQLFIK 281
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKplSESEEEI----KTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFLK 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 282 HERKLHIYVWYCQNKPRSEYIV-------AEYDAYFEEV-KQEINQRLTLSDFLIKPIQRITKYQLLLKDFLRYSEKAGL 353
Cdd:pfam00621  77 FAPGFKVYSTYCSNYPKALKLLkkllkknPKFRAFLEELeANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 156
                         170       180
                  ....*....|....*....|
gi 1039751490 354 ECSDIEKAVELMCLVPKRCN 373
Cdd:pfam00621 157 DYEDLKKALEAIKEVAKQIN 176
SH3_Kalirin_2 cd11853
Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
595-651 3.14e-33

Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. 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: 212787  Cd Length: 59  Bit Score: 121.39  E-value: 3.14e-33
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039751490 595 TMTVIKDYYALKENEICVSQGEVVQVLAVNQQNMCLVYQPASDHSPAAEGWVPGSIL 651
Cdd:cd11853     1 TMPVIQDYYALKEDEICVSQGEVVQILAANQQNMFLVYRPATDQSPAAEGWIPGSVL 57
SH3-RhoG_link super family cl24983
SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved ...
25-201 6.14e-29

SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved residues from higher eukaryotes is found to lie between an SH3 pfam00018 and the RhoGEF, pfam00621, domains. It is serine-rich and likely to be acidic and natively unstructured.


The actual alignment was detected with superfamily member pfam16609:

Pssm-ID: 465196  Cd Length: 261  Bit Score: 116.05  E-value: 6.14e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  25 FPCRDSYSHSSSENGgKSESVAHLQSQPSLNSiHSSPGPKRSTNTLKKWLTSPVRRLNSGKADGNIK----KQKKVRDGR 100
Cdd:pfam16609  17 FNHKDTLSVYSNDSI-MPGSSATLQPGHGISS-HASPGPKRPGNTLRKWLTSPVRRLSSGKADGHVKklahKHKKSREVR 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 101 KS--FDLGSPKPGDET--TPQGDSADEKSK-----------------KGWGEDEPDEESHT-PLPPPMKIFDNDPTQDEM 158
Cdd:pfam16609  95 KSreITAGSQKDSDDSaaTPQDETVEERVRneglssgtlskssssgmQSCGEEEGEEGADSvPLPPPMAIQQHSLLQPDS 174
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1039751490 159 TLEGGSYRGSLKdPTGclneGMTPPTPP--RNLEEEQKAK-ALRGR 201
Cdd:pfam16609 175 QDDKTSSRLFVR-PSS----SETPSAAElvSAIEELVKSKmALEDR 215
 
Name Accession Description Interval E-value
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
378-512 1.80e-73

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270061  Cd Length: 140  Bit Score: 232.92  E-value: 1.80e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 378 LGRLQGFEGTLTAQGKLLQQDTFYVIELDAGMQSRTKERRVFLFEQIVIFSELLRKGS--LTPGYMFKRSIKMNYLVLED 455
Cdd:cd13241     1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAGLLQKGKERRVFLFEQIIIFSEILGKKTqfSNPGYIYKNHIKVNKMSLEE 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 456 NVDGDPCKFALMNRE---TSERVILQAANSDIQQAWVQDINQVLETQRDFLNALQSPIEY 512
Cdd:cd13241    81 NVDGDPLRFALKSRDpnnPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
204-373 3.35e-51

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 175.18  E-value: 3.35e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 204 VLNELVQTEKDYVKDLGIVVEGFMKRIEE--KGVPEDMrgkeKIVFGNIHQIYDWHKDFFLAELEKCIQEQDRLAQLFIK 281
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKplSESEEEI----KTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFLK 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 282 HERKLHIYVWYCQNKPRSEYIV-------AEYDAYFEEV-KQEINQRLTLSDFLIKPIQRITKYQLLLKDFLRYSEKAGL 353
Cdd:pfam00621  77 FAPGFKVYSTYCSNYPKALKLLkkllkknPKFRAFLEELeANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 156
                         170       180
                  ....*....|....*....|
gi 1039751490 354 ECSDIEKAVELMCLVPKRCN 373
Cdd:pfam00621 157 DYEDLKKALEAIKEVAKQIN 176
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
201-373 7.88e-48

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 166.32  E-value: 7.88e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 201 RMFVLNELVQTEKDYVKDLGIVVEGFMKRIEEKGVPeDMRGKEKIVFGNIHQIYDWHKDFfLAELEKCIQEQD----RLA 276
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP-LSPEEVELLFGNIEEIYEFHRIF-LKSLEERVEEWDksgpRIG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 277 QLFIKHERKLHIYVWYCQNKPRSEYIVAEYDA---YFEEVKQEIN---QRLTLSDFLIKPIQRITKYQLLLKDFLRYSEK 350
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnkFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158
                         170       180
                  ....*....|....*....|...
gi 1039751490 351 AGLECSDIEKAVELMCLVPKRCN 373
Cdd:cd00160   159 GHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
204-374 1.02e-47

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 165.94  E-value: 1.02e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  204 VLNELVQTEKDYVKDLGIVVEGFMKRIEEKGVPEDMRgKEKIVFGNIHQIYDWHKDFfLAELEKCIQE----QDRLAQLF 279
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPN-ELETLFGNIEEIYEFHRDF-LDELEERIEEwddsVERIGDVF 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  280 IKHERKLHIYVWYCQNKPRSEYIVAE------YDAYFEEV-KQEINQRLTLSDFLIKPIQRITKYQLLLKDFLRYSEKAG 352
Cdd:smart00325  79 LKLEEFFKIYSEYCSNHPDALELLKKlkknprFQKFLKEIeSSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158
                          170       180
                   ....*....|....*....|..
gi 1039751490  353 LECSDIEKAVELMCLVPKRCND 374
Cdd:smart00325 159 EDREDLKKALKAIKELANQVNE 180
SH3_Kalirin_2 cd11853
Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
595-651 3.14e-33

Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. 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: 212787  Cd Length: 59  Bit Score: 121.39  E-value: 3.14e-33
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039751490 595 TMTVIKDYYALKENEICVSQGEVVQVLAVNQQNMCLVYQPASDHSPAAEGWVPGSIL 651
Cdd:cd11853     1 TMPVIQDYYALKEDEICVSQGEVVQILAANQQNMFLVYRPATDQSPAAEGWIPGSVL 57
SH3-RhoG_link pfam16609
SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved ...
25-201 6.14e-29

SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved residues from higher eukaryotes is found to lie between an SH3 pfam00018 and the RhoGEF, pfam00621, domains. It is serine-rich and likely to be acidic and natively unstructured.


Pssm-ID: 465196  Cd Length: 261  Bit Score: 116.05  E-value: 6.14e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  25 FPCRDSYSHSSSENGgKSESVAHLQSQPSLNSiHSSPGPKRSTNTLKKWLTSPVRRLNSGKADGNIK----KQKKVRDGR 100
Cdd:pfam16609  17 FNHKDTLSVYSNDSI-MPGSSATLQPGHGISS-HASPGPKRPGNTLRKWLTSPVRRLSSGKADGHVKklahKHKKSREVR 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 101 KS--FDLGSPKPGDET--TPQGDSADEKSK-----------------KGWGEDEPDEESHT-PLPPPMKIFDNDPTQDEM 158
Cdd:pfam16609  95 KSreITAGSQKDSDDSaaTPQDETVEERVRneglssgtlskssssgmQSCGEEEGEEGADSvPLPPPMAIQQHSLLQPDS 174
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1039751490 159 TLEGGSYRGSLKdPTGclneGMTPPTPP--RNLEEEQKAK-ALRGR 201
Cdd:pfam16609 175 QDDKTSSRLFVR-PSS----SETPSAAElvSAIEELVKSKmALEDR 215
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
192-365 3.53e-11

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 66.84  E-value: 3.53e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  192 EQKAKALRGRMFVLNELVQTEKDYVKDLGIVVEGFMKRIEE-KGVPEDMRGK-EKIVFGNIHQIYDWHKDFF--LAELEK 267
Cdd:COG5422    476 ESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEEsNIIPENARRNfIKHVFANINEIYAVNSKLLkaLTNRQC 555
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  268 CIQEQDRLAQLFIKHERKLHIYVWYCQNKPRSEYI----------VAEYDAYFEEVKQeiNQRLTLSDFLIKPIQRITKY 337
Cdd:COG5422    556 LSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEfereksvnpnFARFDHEVERLDE--SRKLELDGYLTKPTTRLARY 633
                          170       180
                   ....*....|....*....|....*...
gi 1039751490  338 QLLLKDFLRYSEKAGLECSDIEKAVELM 365
Cdd:COG5422    634 PLLLEEVLKFTDPDNPDTEDIPKVIDML 661
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
401-496 1.32e-05

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 44.46  E-value: 1.32e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  401 YVIELDAGMQSRTKERRVFLFEQIVIFSellRKGSLTPGYMFKRSIKMNYLVLEDNVDGD----PCKFALMNRETsERVI 476
Cdd:smart00233   6 WLYKKSGGGKKSWKKRYFVLFNSTLLYY---KSKKDKKSYKPKGSIDLSGCTVREAPDPDsskkPHCFEIKTSDR-KTLL 81
                           90       100
                   ....*....|....*....|
gi 1039751490  477 LQAANSDIQQAWVQDINQVL 496
Cdd:smart00233  82 LQAESEEEREKWVEALRKAI 101
PH_19 pfam19057
PH domain; This entry contains a PH domain found in RhoGEF proteins.
385-446 2.15e-05

PH domain; This entry contains a PH domain found in RhoGEF proteins.


Pssm-ID: 465965  Cd Length: 151  Bit Score: 45.14  E-value: 2.15e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 385 EGTLTAQGKLLQQDTFYVIEL-DAGMQSRTKERRVFLFEQIVIFSELLRKGS-------LTPGYMFKRSI 446
Cdd:pfam19057   4 KLLSSGQRYLIRQDDVVETVYnERGEVLKSKERRLFLLNDLLVCVTVNSKSGsdfgslpGGEKYKLKWSV 73
 
Name Accession Description Interval E-value
PH2_Kalirin_Trio_p63RhoGEF cd13241
p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor ...
378-512 1.80e-73

p63RhoGEF pleckstrin homology (PH) domain, repeat 2; The guanine nucleotide exchange factor p63RhoGEF is an effector of the heterotrimeric G protein, Galphaq and linking Galphaq-coupled receptors (GPCRs) to the activation of RhoA. The Dbl(DH) and PH domains of p63RhoGEF interact with the effector-binding site and the C-terminal region of Galphaq and appear to relieve autoinhibition of the catalytic DH domain by the PH domain. Trio, Duet, and p63RhoGEF are shown to constitute a family of Galphaq effectors that appear to activate RhoA both in vitro and in intact cells. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270061  Cd Length: 140  Bit Score: 232.92  E-value: 1.80e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 378 LGRLQGFEGTLTAQGKLLQQDTFYVIELDAGMQSRTKERRVFLFEQIVIFSELLRKGS--LTPGYMFKRSIKMNYLVLED 455
Cdd:cd13241     1 VGRLQGFDGKITAQGKLLLQGTLLVSEPSAGLLQKGKERRVFLFEQIIIFSEILGKKTqfSNPGYIYKNHIKVNKMSLEE 80
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 456 NVDGDPCKFALMNRE---TSERVILQAANSDIQQAWVQDINQVLETQRDFLNALQSPIEY 512
Cdd:cd13241    81 NVDGDPLRFALKSRDpnnPSETFILQAASPEVRQEWVDTINQILDTQRDFLKALQSPIAY 140
RhoGEF pfam00621
RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called ...
204-373 3.35e-51

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 459876 [Multi-domain]  Cd Length: 176  Bit Score: 175.18  E-value: 3.35e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 204 VLNELVQTEKDYVKDLGIVVEGFMKRIEE--KGVPEDMrgkeKIVFGNIHQIYDWHKDFFLAELEKCIQEQDRLAQLFIK 281
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEVFLPPNSKplSESEEEI----KTIFSNIEEIYELHRQLLLEELLKEWISIQRIGDIFLK 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 282 HERKLHIYVWYCQNKPRSEYIV-------AEYDAYFEEV-KQEINQRLTLSDFLIKPIQRITKYQLLLKDFLRYSEKAGL 353
Cdd:pfam00621  77 FAPGFKVYSTYCSNYPKALKLLkkllkknPKFRAFLEELeANPECRGLDLNSFLIKPVQRIPRYPLLLKELLKHTPPDHP 156
                         170       180
                  ....*....|....*....|
gi 1039751490 354 ECSDIEKAVELMCLVPKRCN 373
Cdd:pfam00621 157 DYEDLKKALEAIKEVAKQIN 176
RhoGEF cd00160
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous ...
201-373 7.88e-48

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.


Pssm-ID: 238091 [Multi-domain]  Cd Length: 181  Bit Score: 166.32  E-value: 7.88e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 201 RMFVLNELVQTEKDYVKDLGIVVEGFMKRIEEKGVPeDMRGKEKIVFGNIHQIYDWHKDFfLAELEKCIQEQD----RLA 276
Cdd:cd00160     1 RQEVIKELLQTERNYVRDLKLLVEVFLKPLDKELLP-LSPEEVELLFGNIEEIYEFHRIF-LKSLEERVEEWDksgpRIG 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 277 QLFIKHERKLHIYVWYCQNKPRSEYIVAEYDA---YFEEVKQEIN---QRLTLSDFLIKPIQRITKYQLLLKDFLRYSEK 350
Cdd:cd00160    79 DVFLKLAPFFKIYSEYCSNHPDALELLKKLKKfnkFFQEFLEKAEsecGRLKLESLLLKPVQRLTKYPLLLKELLKHTPD 158
                         170       180
                  ....*....|....*....|...
gi 1039751490 351 AGLECSDIEKAVELMCLVPKRCN 373
Cdd:cd00160   159 GHEDREDLKKALEAIKEVASQVN 181
RhoGEF smart00325
Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange ...
204-374 1.02e-47

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.


Pssm-ID: 214619 [Multi-domain]  Cd Length: 180  Bit Score: 165.94  E-value: 1.02e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  204 VLNELVQTEKDYVKDLGIVVEGFMKRIEEKGVPEDMRgKEKIVFGNIHQIYDWHKDFfLAELEKCIQE----QDRLAQLF 279
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKLLSPN-ELETLFGNIEEIYEFHRDF-LDELEERIEEwddsVERIGDVF 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  280 IKHERKLHIYVWYCQNKPRSEYIVAE------YDAYFEEV-KQEINQRLTLSDFLIKPIQRITKYQLLLKDFLRYSEKAG 352
Cdd:smart00325  79 LKLEEFFKIYSEYCSNHPDALELLKKlkknprFQKFLKEIeSSPQCRRLTLESLLLKPVQRLTKYPLLLKELLKHTPEDH 158
                          170       180
                   ....*....|....*....|..
gi 1039751490  353 LECSDIEKAVELMCLVPKRCND 374
Cdd:smart00325 159 EDREDLKKALKAIKELANQVNE 180
SH3_Kalirin_2 cd11853
Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
595-651 3.14e-33

Second Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. 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: 212787  Cd Length: 59  Bit Score: 121.39  E-value: 3.14e-33
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039751490 595 TMTVIKDYYALKENEICVSQGEVVQVLAVNQQNMCLVYQPASDHSPAAEGWVPGSIL 651
Cdd:cd11853     1 TMPVIQDYYALKEDEICVSQGEVVQILAANQQNMFLVYRPATDQSPAAEGWIPGSVL 57
SH3-RhoG_link pfam16609
SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved ...
25-201 6.14e-29

SH3-RhoGEF linking unstructured region; This family of natively unstructured but conserved residues from higher eukaryotes is found to lie between an SH3 pfam00018 and the RhoGEF, pfam00621, domains. It is serine-rich and likely to be acidic and natively unstructured.


Pssm-ID: 465196  Cd Length: 261  Bit Score: 116.05  E-value: 6.14e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  25 FPCRDSYSHSSSENGgKSESVAHLQSQPSLNSiHSSPGPKRSTNTLKKWLTSPVRRLNSGKADGNIK----KQKKVRDGR 100
Cdd:pfam16609  17 FNHKDTLSVYSNDSI-MPGSSATLQPGHGISS-HASPGPKRPGNTLRKWLTSPVRRLSSGKADGHVKklahKHKKSREVR 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 101 KS--FDLGSPKPGDET--TPQGDSADEKSK-----------------KGWGEDEPDEESHT-PLPPPMKIFDNDPTQDEM 158
Cdd:pfam16609  95 KSreITAGSQKDSDDSaaTPQDETVEERVRneglssgtlskssssgmQSCGEEEGEEGADSvPLPPPMAIQQHSLLQPDS 174
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1039751490 159 TLEGGSYRGSLKdPTGclneGMTPPTPP--RNLEEEQKAK-ALRGR 201
Cdd:pfam16609 175 QDDKTSSRLFVR-PSS----SETPSAAElvSAIEELVKSKmALEDR 215
PH_puratrophin-1 cd13242
Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell ...
373-499 3.81e-21

Puratrophin-1 pleckstrin homology (PH) domain; Puratrophin-1 (also called Purkinje cell atrophy-associated protein 1 or PLEKHG4/Pleckstrin homology domain-containing family G member 4) contains a spectrin repeat, a RhoGEF (DH) domain, and a PH domain. It is thought to function in intracellular signaling and cytoskeleton dynamics at the Golgi. Puratrophin-1 is expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. A single nucleotide substitution in the puratrophin-1 gene were once thought to result in autosomal dominant cerebellar ataxia (ADCA), but now it has been demonstrated that this ataxia is a result of defects in the BEAN gene. Puratrophin contains a domain architecture similar to that of Dbl family members Dbs and Trio. Dbs is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a RhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Trio is a multidomain signaling protein that contains two RhoGEF(DH)-PH domains in tandem. 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: 270062  Cd Length: 136  Bit Score: 89.66  E-value: 3.81e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 373 NDMMNLGRLQGFEGTLTAQGKLLQQDTFYVIeldagmQSRTK-ERRVFLFEQIVIFSELLRKGSLTPGYMFKRSIKMNYL 451
Cdd:cd13242     8 NDLLAMDSIRGCDVNLKEQGQLLRQDEFLVW------QGRKKcLRHVFLFEDLILFSKPKKTPGGKDVYIYKHSIKTSDI 81
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1039751490 452 VLEDNVDGDPCKFAL--MNRETSERVILQAANSDIQQAWVQDINQVLETQ 499
Cdd:cd13242    82 GLTENVGDSGLKFEIwfRRRKARDTYILQATSPEIKQAWTSDIAKLLWKQ 131
PH_Dbs cd01227
DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming ...
383-499 6.76e-17

DBL's big sister protein pleckstrin homology (PH) domain; Dbs (also called MCF2-transforming sequence-like protein 2) is a guanine nucleotide exchange factor (GEF), which contains spectrin repeats, a rhoGEF (DH) domain and a PH domain. The Dbs PH domain participates in binding to both the Cdc42 and RhoA GTPases. 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: 269934 [Multi-domain]  Cd Length: 126  Bit Score: 77.24  E-value: 6.76e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 383 GFEGTLTAQGKLLQQDTFYV-IELDAG-----MQSRTKERRVFLFEQIVIFSELLRKGSLTPGYMFKRSIKMNYLVLEDN 456
Cdd:cd01227     4 GYDGNLGDLGKLLMQGSFNVwTEHKKGhtkklARFKPMQRHIFLYEKAVLFCKKRGENGEAPSYSYKNSLNTTAVGLTEN 83
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1039751490 457 VDGDPCKFALMNRETSERVILQAANSDIQQAWVQDINQVLETQ 499
Cdd:cd01227    84 VKGDTKKFEIWLNGREEVFIIQAPTPEIKAAWVKAIRQVLLSQ 126
PH1_Kalirin_Trio_like cd13240
Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; ...
381-497 1.40e-16

Triple functional domain pleckstrin homology pleckstrin homology (PH) domain, repeat 1; RhoGEFs, Kalirin and Trio, the mammalian homologs of Drosophila Trio and Caenorhabditis elegans UNC-73 regulate a novel step in secretory granule maturation. Their signaling modulates the extent to which regulated cargo enter and remain in the regulated secretory pathway. This allows for fine tuning of peptides released by a single secretory cell type with impaired signaling leading to pathological states. Trio plays an essential role in regulating the actin cytoskeleton during axonal guidance and branching. Kalirin and Trio are encoded by separate genes in mammals and by a single one in invertebrates. Kalirin and Trio share the same complex multidomain structure and display several splice variants. The longest Kalirin and Trio proteins have a Sec14 domain, a stretch of spectrin repeats, a RhoGEF(DH)/PH cassette (also called GEF1), an SH3 domain, a second RhoGEF(DH)/PH cassette (also called GEF2), a second SH3 domain, Ig/FNIII domains, and a kinase domain. The first RhoGEF(DH)/PH cassette catalyzes exchange on Rac1 and RhoG while the second RhoGEF(DH)/PH cassette is specific for RhoA. Kalirin and Trio are closely related to p63RhoGEF and have PH domains of similar function. 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.


Pssm-ID: 270060  Cd Length: 123  Bit Score: 76.27  E-value: 1.40e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 381 LQGFEGTLTAQGKLLQQDTFYVIELDAgMQSRTKERRVFLFEQIVIFSELLRKGSLTPGYMFKRSIKMNYLVLEDNVDGD 460
Cdd:cd13240     2 LEGCDEDLDSLGEVILQDSFQVWDPKQ-LIRKGRERHVFLFELCLVFSKEVKDSNGKSKYIYKSRLMTSEIGVTEHIEGD 80
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039751490 461 PCKFALMNRE--TSE-RVILQAANSDIQQAWVQDINQVLE 497
Cdd:cd13240    81 PCKFALWTGRvpTSDnKIVLKASSLEVKQTWVKKLREVIQ 120
PH_Obscurin cd13239
Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; ...
381-492 2.83e-11

Obscurin pleckstrin homology (PH) domain; Obscurin (also called Obscurin-RhoGEF; Obscurin-myosin light chain kinase/Obscurin-MLCK) is a giant muscle protein that is concentrated at the peripheries of Z-disks and M-lines. It binds small ankyrin I, a component of the sarcoplasmic reticulum (SR) membrane. It is associated with the contractile apparatus through binding with titin and sarcomeric myosin. It plays important roles in the organization and assembly of the myofibril and the SR. Obscurin has been observed as alternatively-spliced isoforms. The major isoform in sleletal muscle, approximately 800 kDa in size, is composed of many adhesion modules and signaling domains. It harbors 49 Ig and 2 FNIII repeats at the N-terminues, a complex middle region with additional Ig domains, an IQ motif, and a conserved SH3 domain near RhoGEF and PH domains, and a non-modular C-terminus with phosphorylation motifs. The obscurin gene also encodes two kinase domains, which are not part of the 800 kDa form of the protein, but is part of smaller spliced products that present in heart muscle. 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: 270059  Cd Length: 125  Bit Score: 61.41  E-value: 2.83e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 381 LQGFEGTLTAQGKLLQQDTFYVIELDAG--MQSRTKERRVFLFEQIVIFSELLRKGSL-TPGYMFKRSIKMNYLVLEDNV 457
Cdd:cd13239     2 IENYPAPLQALGEPIRQGHFTVWEEAPEvkTSSRGHHRHVFLFKNCVVICKPKRDSRTdTVTYVFKNKMKLSDIDVKDTV 81
                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1039751490 458 DGDPCKFALMN--RETSERVILQAANSDIQQAWVQDI 492
Cdd:cd13239    82 EGDDRSFGLWHehRGSVRKYTLQARSAIIKSSWLKDL 118
ROM1 COG5422
RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction ...
192-365 3.53e-11

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];


Pssm-ID: 227709 [Multi-domain]  Cd Length: 1175  Bit Score: 66.84  E-value: 3.53e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  192 EQKAKALRGRMFVLNELVQTEKDYVKDLGIVVEGFMKRIEE-KGVPEDMRGK-EKIVFGNIHQIYDWHKDFF--LAELEK 267
Cdd:COG5422    476 ESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEEsNIIPENARRNfIKHVFANINEIYAVNSKLLkaLTNRQC 555
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  268 CIQEQDRLAQLFIKHERKLHIYVWYCQNKPRSEYI----------VAEYDAYFEEVKQeiNQRLTLSDFLIKPIQRITKY 337
Cdd:COG5422    556 LSPIVNGIADIFLDYVPKFEPFIKYGASQPYAKYEfereksvnpnFARFDHEVERLDE--SRKLELDGYLTKPTTRLARY 633
                          170       180
                   ....*....|....*....|....*...
gi 1039751490  338 QLLLKDFLRYSEKAGLECSDIEKAVELM 365
Cdd:COG5422    634 PLLLEEVLKFTDPDNPDTEDIPKVIDML 661
SH3_Kalirin_1 cd11852
First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or ...
598-651 5.82e-08

First Src homology 3 domain of the RhoGEF kinase, Kalirin; Kalirin, also called Duo, Duet, or TRAD, is a large neuronal dual Rho guanine nucleotide exchange factor (RhoGEF) that activates Rac1, RhoA, and RhoG using two RhoGEF domains. Kalirin exists in many isoforms generated by alternative splicing and the use of multiple promoters; the major isoforms are kalirin-7, -9, and -12, which differ at their C-terminal ends. Kalirin-12, the longest isoform, contains an N-terminal Sec14p domain, spectrin-like repeats, two RhoGEF domains, two SH3 domains, as well as Ig, FNIII, and kinase domains at the C-terminal end. Kalirin-7 contains only a single RhoGEF domain and does not contain an SH3 domain. Kalirin, through its many isoforms, interacts with many different proteins and is able to localize to different locations within the cell. It influences neurite initiation, axon growth, dendritic morphogenesis, vesicle trafficking, neuronal maintenance, and neurodegeneration. 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: 212786  Cd Length: 62  Bit Score: 49.70  E-value: 5.82e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039751490 598 VIKDYYALKENEICVSQGEVVQVL--AVNQQNMCLVYQPASDHSPAAEGWVPGSIL 651
Cdd:cd11852     5 VIEDFEATSSQELTVSKGQTVEVLerPSSRPDWCLVRTLEQDNSPPQEGLVPSSIL 60
PH_PLEKHG1_G2_G3 cd13243
Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) ...
356-496 2.57e-06

Pleckstrin homology domain-containing family G members 1, 2, and 3 pleckstrin homology (PH) domain; PLEKHG1 (also called ARHGEF41), PLEKHG2 (also called ARHGEF42 or CLG/common-site lymphoma/leukemia guanine nucleotide exchange factor2), and PLEKHG3 (also called ARHGEF43) have RhoGEF DH/double-homology domains in tandem with a PH domain which is involved in phospholipid binding. They function as a guanine nucleotide exchange factor (GEF) and are involved in the regulation of Rho protein signal transduction. Mutations in PLEKHG1 have been associated panic disorder (PD), an anxiety disorder characterized by panic attacks and anticipatory anxiety. 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: 270063 [Multi-domain]  Cd Length: 147  Bit Score: 47.73  E-value: 2.57e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 356 SDIEKAVELMCLVPKRCNDM-------MNLGRLQ----GFEG-TLTAQGKLLQQDTFyvieldaGMQSRTKERRVFLFEQ 423
Cdd:cd13243     2 SVVEEALDTMTQVAWHINDMkrkhehaVRVQEIQslldGWEGpELTTYGDLVLEGTF-------RMAGAKNERLLFLFDK 74
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1039751490 424 IVifseLLRKGSLTPGYMFKRSIKMNYLVLEDNVDGDPCKFALMNRETSE-RVILQAANSDIQQAWVQDINQVL 496
Cdd:cd13243    75 ML----LITKKREDGILQYKTHIMCSNLMLSESIPKEPLSFQVLPFDNPKlQYTLQAKNQEQKRLWTQEIKRLI 144
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
401-496 1.32e-05

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 44.46  E-value: 1.32e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490  401 YVIELDAGMQSRTKERRVFLFEQIVIFSellRKGSLTPGYMFKRSIKMNYLVLEDNVDGD----PCKFALMNRETsERVI 476
Cdd:smart00233   6 WLYKKSGGGKKSWKKRYFVLFNSTLLYY---KSKKDKKSYKPKGSIDLSGCTVREAPDPDsskkPHCFEIKTSDR-KTLL 81
                           90       100
                   ....*....|....*....|
gi 1039751490  477 LQAANSDIQQAWVQDINQVL 496
Cdd:smart00233  82 LQAESEEEREKWVEALRKAI 101
PH_19 pfam19057
PH domain; This entry contains a PH domain found in RhoGEF proteins.
385-446 2.15e-05

PH domain; This entry contains a PH domain found in RhoGEF proteins.


Pssm-ID: 465965  Cd Length: 151  Bit Score: 45.14  E-value: 2.15e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 385 EGTLTAQGKLLQQDTFYVIEL-DAGMQSRTKERRVFLFEQIVIFSELLRKGS-------LTPGYMFKRSI 446
Cdd:pfam19057   4 KLLSSGQRYLIRQDDVVETVYnERGEVLKSKERRLFLLNDLLVCVTVNSKSGsdfgslpGGEKYKLKWSV 73
PH_unc89 cd13325
unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest ...
386-494 1.20e-04

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. 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: 270134  Cd Length: 114  Bit Score: 41.95  E-value: 1.20e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 386 GTLTAQGKLLQQDTFYVIEldagMQSRTKERRVFLFEQIVIFSELLRKGSLTPGYMFKRSIKMNYLVLEDnVDGDPCKFA 465
Cdd:cd13325     1 GNIHKLGRLLRHDWFTVTD----GEGKAKERYLFLFKSRILITKVRRISEDRSVFILKDIIRLPEVNVKQ-HPDDERTFE 75
                          90       100       110
                  ....*....|....*....|....*....|..
gi 1039751490 466 LMNRETSER--VILQAANSD-IQQAWVQDINQ 494
Cdd:cd13325    76 LQPKLPAFGilPIDFKAHKDeIKDYWLNEIEE 107
PH pfam00169
PH domain; PH stands for pleckstrin homology.
411-497 4.73e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 39.85  E-value: 4.73e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 411 SRTKERRVFLFE-QIVIFSELLRKGSLTPgymfKRSIKMN----YLVLEDNVDGDPCKFALM--NRETSERVILQAANSD 483
Cdd:pfam00169  16 KSWKKRYFVLFDgSLLYYKDDKSGKSKEP----KGSISLSgcevVEVVASDSPKRKFCFELRtgERTGKRTYLLQAESEE 91
                          90
                  ....*....|....
gi 1039751490 484 IQQAWVQDINQVLE 497
Cdd:pfam00169  92 ERKDWIKAIQSAIR 105
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
401-492 6.45e-04

Pleckstrin homology (PH) domain; 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: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 39.45  E-value: 6.45e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 401 YVIELDAGMQSRTKERRVFLFEQIVIFSellrKGSLTPGYMFKRSIKMN--YLVLEDNVDGDPCKFALmNRETSERVILQ 478
Cdd:cd00821     4 YLLKRGGGGLKSWKKRWFVLFEGVLLYY----KSKKDSSYKPKGSIPLSgiLEVEEVSPKERPHCFEL-VTPDGRTYYLQ 78
                          90
                  ....*....|....
gi 1039751490 479 AANSDIQQAWVQDI 492
Cdd:cd00821    79 ADSEEERQEWLKAL 92
PH_RhoGEF3_XPLN cd10572
Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain; RhoGEF3/XPLN, a Rho ...
418-495 3.19e-03

Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain; RhoGEF3/XPLN, a Rho family GEF, preferentially stimulates guanine nucleotide exchange on RhoA and RhoB, but not RhoC, RhoG, Rac1, or Cdc42 in vitro. It also possesses transforming activity. RhoGEF3/XPLN contains a tandem Dbl homology and PH domain, but lacks homology with other known functional domains or motifs. It is expressed in the brain, skeletal muscle, heart, kidney, platelets, and macrophage and neuronal cell lines. 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: 269976  Cd Length: 133  Bit Score: 38.11  E-value: 3.19e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039751490 418 VFLFEQIVIFSELLRKGSLTPGYMFKRSIKMNYLVLEDNVDGDP-----CKFALMNRETSERVI--------------LQ 478
Cdd:cd10572    36 VFLFEEVLVLTRPVTRNEQLCYQVYRQPIPVADLVLEDLPDGEVrlggsFRGAFSNNERAKNFFrvsftdrslgqshtLQ 115
                          90
                  ....*....|....*..
gi 1039751490 479 AANSDIQQAWVQDINQV 495
Cdd:cd10572   116 ANDEFDKQQWLNCIRQA 132
SH3_Tks_1 cd12015
First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; Tks proteins are Src ...
597-651 3.54e-03

First Src homology 3 domain of Tyrosine kinase substrate (Tks) proteins; 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. Vertebrates contain two Tks proteins, Tks4 (Tyr kinase substrate with four SH3 domains) and Tks5 (Tyr kinase substrate with five SH3 domains), which display partially overlapping but non-redundant functions. Both associate with the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. Tks5 interacts with N-WASP and Nck, while Tks4 is essential for the localization of MT1-MMP (membrane-type 1 matrix metalloproteinase) to invadopodia. Tks proteins contain an N-terminal Phox homology (PX) domain and four or five SH3 domains. This model characterizes the first SH3 domain of Tks 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: 212948  Cd Length: 53  Bit Score: 35.86  E-value: 3.54e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039751490 597 TVIKDYYALKENEICVSQGEVVQVLAVNQQNMCLVyqpasdHSPAAEGWVPGSIL 651
Cdd:cd12015     3 VVVADYKKQQPNEISLRAGDVVDVIEKNENGWWFV------SLEDEQGWVPATYL 51
 
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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