NCBI Conserved Domain Search

Conserved domains on [gi|823429468|ref|XP_012422060|]

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PREDICTED: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 isoform X1 [Odobenus rosmarus divergens]

Protein Classification

PLC family C2 domain-containing protein( domain architecture ID 11598547)

PLC (phosphoinositide-specific phospholipase C) family C2 domain-containing protein similar to C2 domain region of PLCs that 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)

Graphical summary

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List of domain hits

Name

Accession

Description

Interval

E-value

PI-PLCc_delta

cd08593

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...

316-617

2.10e-170

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: 491.47 E-value: 2.10e-170

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08593    1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQlkgkillkgkklggllppggeggp 475
Cdd:cd08593   81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVLTALPSPEE------------------------ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 476 eatvvsdedeaaeiedeaVRSRVQRKPRedKLRLVKELSDMVIYCKSVHFGGFSSPGTPGQaFYEMVSFSENRALRLLQE 555
Cdd:cd08593  137 ------------------LKGKILVKGK--KLKLAKELSDLVIYCKSVHFKSFEHSKENYH-FYEMSSFSESKALKLAQE 195

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 823429468 556 SGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08593  196 SGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

EFh_PI-PLCdelta1

cd16217

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...

165-304

2.74e-83

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (PLCD1), or phospholipase C-III (PLC-III), or phospholipase C-delta-1 (PLC-delta-1), is present in high abundancy in the brain, heart, lung, skeletal muscle and testis. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. PI-PLC-delta1 is required for maintenance of homeostasis in skin and metabolic tissues. Moreover, it is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta1 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta1 can be positively or negatively regulated by several binding partners, including p122/Rho GTPase activating protein (RhoGAP), Gha/Transglutaminase II, RalA, and calmodulin. It is involved in Alzheimer's disease and hypertension. Furthermore, PI-PLC-delta1 regulates cell proliferation and cell-cycle progression from G1- to S-phase by control of cyclin E-CDK2 activity and p27 levels. It can be activated by alpha1-adrenoreceptors (AR) in a calcium-dependent manner and may be important for G protein-coupled receptors (GPCR) responses in vascular smooth muscle (VSM). PI-PLC-delta1 may also be involved in noradrenaline (NA)-induced phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis and modulate sustained contraction of mesenteric small arteries. In addition, it inhibits thermogenesis and induces lipid accumulation, and therefore contributes to the development of obesity. PI-PLC-delta1 contains 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 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. PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. In addition, PI-PLC-delta1 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, as well as a nuclear localization signal within its linker region, both of which may be responsible for translocating PI-PLC-delta1 into and out of the cell nucleus.

Pssm-ID: 320047 [Multi-domain] Cd Length: 139 Bit Score: 261.60 E-value: 2.74e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKMLTQREEIDRTFAEAAG 244
Cdd:cd16217    1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSKSGFLEGEEIEEFYKLLTKREEIDVIFGEYAK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 245 SREMLSVDQLVTFLQHQQREEaAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16217   81 SDGTMSRNNLLNFLQEEQREE-VAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139

PH_PLC_delta

cd13363

Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...

43-160

3.75e-68

Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) consists of three family members, delta 1, 2, and 3. PLC-delta1 is the most well studied. PLC-delta is activated by high calcium levels generated by other PLC family members, and functions as a calcium amplifier within the cell. PLC-delta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, and a C-terminal C2 domain. The PH domain binds PIP2 and promotes activation of the catalytic core as well as tethering the enzyme to the plasma membrane. The C2 domain has been shown to mediate calcium-dependent phospholipid binding as well. The PH and C2 domains operate in concert as a "tether and fix" apparatus necessary for processive catalysis by the enzyme. Its leucine-rich nuclear export signal (NES) in its EF hand motif, as well as a Nuclear localization signal within its linker region allow PLC-delta 1 to actively translocate into and out of the nucleus. 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: 270169 Cd Length: 117 Bit Score: 220.65 E-value: 3.75e-68

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  43 LLKGSQLLKVKSNSWRRERFYKLQEDCKTIWQESRKvMRTPESQLFSIEDIQEVRKGHRTEGMEKFARDVPEDRCFSIVF 122
Cdd:cd13363    1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKK-TRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVF 79

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 823429468 123 KDQRNTLDLIAPSPAEAQHWVQGLRKIIHHSGSMDQRQ 160
Cdd:cd13363   80 KGRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

685-806

3.21e-54

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: 183.13 E-value: 3.21e-54

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 685 QVISGQQLPKVNKNKNSIVDPKVTVEIHGVGRDV-ASCQTAVVTNNGFNPWWDTEFVFEVVVPELALVRFLVEDYDaSSK 763
Cdd:cd00275    7 KIISGQQLPKPKGDKGSIVDPYVEVEIHGLPADDsAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDED-SGD 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 823429468 764 NDFIGQSTIPLGSLKQGYRHVHLLSKNGDQHPSATLFVKVSLQ 806
Cdd:cd00275   86 DDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

Name

Accession

Description

Interval

E-value

PI-PLCc_delta

cd08593

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...

316-617

2.10e-170

Pssm-ID: 176535 [Multi-domain] Cd Length: 257 Bit Score: 491.47 E-value: 2.10e-170

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08593    1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQlkgkillkgkklggllppggeggp 475
Cdd:cd08593   81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVLTALPSPEE------------------------ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 476 eatvvsdedeaaeiedeaVRSRVQRKPRedKLRLVKELSDMVIYCKSVHFGGFSSPGTPGQaFYEMVSFSENRALRLLQE 555
Cdd:cd08593  137 ------------------LKGKILVKGK--KLKLAKELSDLVIYCKSVHFKSFEHSKENYH-FYEMSSFSESKALKLAQE 195

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 823429468 556 SGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08593  196 SGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

EFh_PI-PLCdelta1

cd16217

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...

165-304

2.74e-83

Pssm-ID: 320047 [Multi-domain] Cd Length: 139 Bit Score: 261.60 E-value: 2.74e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKMLTQREEIDRTFAEAAG 244
Cdd:cd16217    1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSKSGFLEGEEIEEFYKLLTKREEIDVIFGEYAK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 245 SREMLSVDQLVTFLQHQQREEaAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16217   81 SDGTMSRNNLLNFLQEEQREE-VAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139

PI-PLC-X

pfam00388

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...

319-451

7.34e-82

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: 7.34e-82

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  319 MGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIRDYA 398
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 823429468  399 FKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQ 451
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPED 133

PLN02228

Phosphoinositide phospholipase C

233-806

9.33e-78

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 261.89 E-value: 9.33e-78

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 233 EEIDRTFaEAAGSREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSADGSAFSLAh 312
Cdd:PLN02228  24 VSIKRLF-EAYSRNGKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSDTNSPLPMS- 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 313 RRVYQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPN-QEPIIYHGYTFTSKILLCDVL 391
Cdd:PLN02228 102 GQVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSgNAAEVRHGRTLTSHEDLQKCL 181

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 392 RAIRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLdRPLDGVTTSLPSPEQLKGKILLKGKKLGGLLPPGG 471
Cdd:PLN02228 182 NAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLF-RCTSESTKHFPSPEELKNKILISTKPPKEYLESKT 260

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 472 EggpEATVVSDEDEAAEIEDEAVRSRVQRKPREDKLRLVkELSDMViyckSVHFGGFSSP------GTPGQAFyeMVSFS 545
Cdd:PLN02228 261 V---QTTRTPTVKETSWKRVADAENKILEEYKDEESEAV-GYRDLI----AIHAANCKDPlkdclsDDPEKPI--RVSMD 330

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 546 ENRALRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDNGACGYVLK 625
Cdd:PLN02228 331 EQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKK 410

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 626 PAFLRDPNSTFNSraLAQGPwwTRKRLSVRVrpaTTGTGAHgppspLPFLNPHLsfaptqvisgqqlpkvnkNKNSIVDP 705
Cdd:PLN02228 411 PRILLDEHTLFDP--CKRLP--IKTTLKVKI---YTGEGWD-----LDFHLTHF------------------DQYSPPDF 460

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 706 KVTVEIHGVGRDVASCQTAVVTNNGFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKNDFIGQSTIPLGSLKQGYRHVH 785
Cdd:PLN02228 461 FVKIGIAGVPRDTVSYRTETAVDQWFPIWGNDEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRAVR 540

                        570       580
                 ....*....|....*....|.
gi 823429468 786 LLSKNGDQHPSATLFVKVSLQ 806
Cdd:PLN02228 541 LHDRAGKAYKNTRLLVSFALD 561

PLCXc

smart00148

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...

319-451

5.93e-72

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: 231.79 E-value: 5.93e-72

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468   319 MGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIRDYA 398
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 823429468   399 FKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQ 451
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQ 133

PH_PLC_delta

cd13363

Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...

43-160

3.75e-68

Pssm-ID: 270169 Cd Length: 117 Bit Score: 220.65 E-value: 3.75e-68

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  43 LLKGSQLLKVKSNSWRRERFYKLQEDCKTIWQESRKvMRTPESQLFSIEDIQEVRKGHRTEGMEKFARDVPEDRCFSIVF 122
Cdd:cd13363    1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKK-TRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVF 79

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 823429468 123 KDQRNTLDLIAPSPAEAQHWVQGLRKIIHHSGSMDQRQ 160
Cdd:cd13363   80 KGRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

685-806

3.21e-54

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 183.13 E-value: 3.21e-54

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 685 QVISGQQLPKVNKNKNSIVDPKVTVEIHGVGRDV-ASCQTAVVTNNGFNPWWDTEFVFEVVVPELALVRFLVEDYDaSSK 763
Cdd:cd00275    7 KIISGQQLPKPKGDKGSIVDPYVEVEIHGLPADDsAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDED-SGD 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 823429468 764 NDFIGQSTIPLGSLKQGYRHVHLLSKNGDQHPSATLFVKVSLQ 806
Cdd:cd00275   86 DDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

EF-hand_like

pfam09279

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...

225-309

1.32e-46

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are predominantly found in phosphoinositide-specific phospholipase C. They adopt a structure consisting of a core of four alpha helices, in an EF like fold, and are required for functioning of the enzyme.

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 160.49 E-value: 1.32e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  225 FYKMLTQREEIDRTFAEAAGSREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:pfam09279   1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                  ....*
gi 823429468  305 GSAFS 309
Cdd:pfam09279  81 GSIFN 85

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

686-786

2.91e-22

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: 92.17 E-value: 2.91e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468   686 VISGQQLPKvnKNKNSIVDPKVTVEIHGVGRDVAscQTAVVTNNGfNPWWDTEFVFEVVVPELALVRFLVEDYDASSKND 765
Cdd:smart00239   6 IISARNLPP--KDKGGKSDPYVKVSLDGDPKEKK--KTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                           90       100
                   ....*....|....*....|.
gi 823429468   766 FIGQSTIPLGSLKQGYRHVHL 786
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHEKL 101

pfam00168

C2 domain;

686-785

7.34e-19

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 82.37 E-value: 7.34e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  686 VISGQQLPkvNKNKNSIVDPKVTVEIHgvgRDVASCQTAVVtNNGFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKND 765
Cdd:pfam00168   7 VIEAKNLP--PKDGNGTSDPYVKVYLL---DGKQKKKTKVV-KNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80

                          90       100
                  ....*....|....*....|
gi 823429468  766 FIGQSTIPLGSLKQGYRHVH 785
Cdd:pfam00168  81 FIGEVRIPLSELDSGEGLDG 100

smart00233

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...

43-151

1.59e-08

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: 52.94 E-value: 1.59e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468    43 LLKGSQLLKVKS--NSWRRERFYKLQEDCKTIWQESRKVMRTPESQLFSIEDIQeVRKGHRTEGMEKfardvpeDRCFSI 120
Cdd:smart00233   1 VIKEGWLYKKSGggKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCT-VREAPDPDSSKK-------PHCFEI 72

                           90       100       110
                   ....*....|....*....|....*....|.
gi 823429468   121 VFKDqRNTLDLIAPSPAEAQHWVQGLRKIIH 151
Cdd:smart00233  73 KTSD-RKTLLLQAESEEEREKWVEALRKAIA 102

COG5038

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

685-780

5.45e-07

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 53.61 E-value: 5.45e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  685 QVISGQQLPKVNKNKNSivDPKVTVEIHGvgrdvASCQTAVVTNNGFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKN 764
Cdd:COG5038  1045 MLRSGENLPSSDENGYS--DPFVKLFLNE-----KSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKN 1117

                          90
                  ....*....|....*.
gi 823429468  765 DFIGQSTIPLGSLKQG 780
Cdd:COG5038  1118 DLLGTAEIDLSKLEPG 1133

PH_12

pfam16457

Pleckstrin homology domain;

40-147

2.33e-06

Pleckstrin homology domain;

Pssm-ID: 465123 [Multi-domain] Cd Length: 128 Bit Score: 47.64 E-value: 2.33e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468   40 LQALLKGSQLLKVKSNS-WRRERFYKLQEDCKTIW----QESRKVMRTPESQLFSIE--DIQEVRKGHRTEGM---EKFA 109
Cdd:pfam16457   6 LNCLLEGAWFPKVRGRRrKKKYRFCRLSPNRKVLHygdfEEKPTVDPSLESLPEKIDlsDIKEVVTGKECPHVresGKKS 85

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 823429468  110 RDVPEDRCFSIVF-KDQRNTLDLIAPSPAEAQHWVQGLR 147
Cdd:pfam16457  86 KKTSSTLAFSLIYgADEYELLDFVAPSESVAAIWLDGLN 124

FRQ1

COG5126

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

157-266

2.07e-04

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 42.09 E-value: 2.07e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 157 DQRQKLQHWIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKML-TQREEI 235
Cdd:COG5126   26 DFEALFRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALgVSEEEA 105

                         90       100       110
                 ....*....|....*....|....*....|..
gi 823429468 236 DRTFAEAAGSR-EMLSVDQLVTFLQHQQREEA 266
Cdd:COG5126  106 DELFARLDTDGdGKISFEEFVAAVRDYYTPDA 137

Name

Accession

Description

Interval

E-value

PI-PLCc_delta

cd08593

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...

316-617

2.10e-170

Pssm-ID: 176535 [Multi-domain] Cd Length: 257 Bit Score: 491.47 E-value: 2.10e-170

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08593    1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQlkgkillkgkklggllppggeggp 475
Cdd:cd08593   81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVLTALPSPEE------------------------ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 476 eatvvsdedeaaeiedeaVRSRVQRKPRedKLRLVKELSDMVIYCKSVHFGGFSSPGTPGQaFYEMVSFSENRALRLLQE 555
Cdd:cd08593  137 ------------------LKGKILVKGK--KLKLAKELSDLVIYCKSVHFKSFEHSKENYH-FYEMSSFSESKALKLAQE 195

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 823429468 556 SGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08593  196 SGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

PI-PLCc_delta1

cd08629

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...

316-617

5.96e-152

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: 444.48 E-value: 5.96e-152

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08629    1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQlkgkillkgkklggllppggeggp 475
Cdd:cd08629   81 DYAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDGVTTSLPSPEQ------------------------ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 476 eatvvsdedeaaeiedeaVRSRVQRKPRedKLRLVKELSDMVIYCKSVHFGGFSSPGTPGQAFYEMVSFSENRALRLLQE 555
Cdd:cd08629  137 ------------------LKGKILLKGK--KLKLVPELSDMIIYCKSVHFGGFSSPGTSGQAFYEMASFSESRALRLLQE 196

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 823429468 556 SGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08629  197 SGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258

PI-PLCc_eukaryota

cd08558

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...

316-617

8.15e-133

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: 393.74 E-value: 8.15e-133

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08558    1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQlkgkillkgkklggllppggeggp 475
Cdd:cd08558   81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENPVQLPSPEQ------------------------ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 476 eatvvsdedeaaeiedeavrsrvqrkpredkLR---LVKelsdmviyCKSvhfggfsspgtpgqafYEMVSFSENRALRL 552
Cdd:cd08558  137 -------------------------------LKgkiLIK--------GKK----------------YHMSSFSETKALKL 161

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 823429468 553 LQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08558  162 LKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226

PI-PLCc_delta3

cd08630

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...

316-617

2.21e-123

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: 370.89 E-value: 2.21e-123

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08630    1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVT-TSLPSPEQlkgkillkgkklggllppggegg 474
Cdd:cd08630   81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNpEELPSPEE----------------------- 137

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 475 peatvvsdedeaaeiedeaVRSRVQRKPRedKLRLVKELSDMVIYCKSVHFGGF-SSPGTPGQAfyEMVSFSENRALRLL 553
Cdd:cd08630  138 -------------------LKGRVLVKGK--KLQISPELSALAVYCQATRLRTLePAPVQPQPC--QVSSLSERKAKKLI 194

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 823429468 554 QESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08630  195 REAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258

PI-PLCc_delta4

cd08631

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...

316-617

3.87e-122

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: 367.74 E-value: 3.87e-122

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08631    1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVT-TSLPSPEQlkgkillkgkklggllppggegg 474
Cdd:cd08631   81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLpTQLPSPEE----------------------- 137

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 475 peatvvsdedeaaeiedeaVRSRVQRKPRedKLRLVKELSDMVIYCKSVHFGGFSSpGTPGQAFYEMVSFSENRALRLLQ 554
Cdd:cd08631  138 -------------------LRGKILLKGK--KIRLSPELSDCVIYCKSVSFRSFTH-SREHYHFYEISSFTETKARKLIR 195

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 823429468 555 ESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08631  196 EAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258

PI-PLCc_PRIP_metazoa

cd08597

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...

317-617

1.81e-112

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: 342.86 E-value: 1.81e-112

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 317 QDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIRD 396
Cdd:cd08597    2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 397 YAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEqlkgkillkgkklggllppggeggpe 476
Cdd:cd08597   82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGESYLPSPH-------------------------- 135

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 477 atvvsdedeaaeiedeAVRSRVQRKPREDKLR-LVKELSDMVIYCKSVHFGGFSSpGTPGQAFYEMVSFSENRALRLLQE 555
Cdd:cd08597  136 ----------------DLKGKIIIKGKKLKRRkLCKELSDLVSLCKSVRFQDFPT-SAQNQKYWEVCSFSENLARRLANE 198

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 823429468 556 SGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08597  199 FPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260

PI-PLCc_zeta

cd08595

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...

316-617

3.03e-103

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: 318.80 E-value: 3.03e-103

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08595    1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGV-TTSLPSPEqlkgkillkgkklggllppggegg 474
Cdd:cd08595   81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPaTGELPSPE------------------------ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 475 peatvvsdedeaaeiedeAVRSRVQRKpreDKLRLVKELSDMVIYCKSVHFGGFSSpGTPGQAFYEMVSFSENRALRLLQ 554
Cdd:cd08595  137 ------------------ALKFKILVK---NKKKIAKALSDLVIYTKSEKFCSFTH-SRDNQHSYENNSIGENKARKLLK 194

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 823429468 555 ESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08595  195 SSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257

PI-PLCc_beta

cd08591

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...

316-617

8.78e-100

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: 309.65 E-value: 8.78e-100

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDG--PNQEPIIYHGYTFTSKILLCDVLRA 393
Cdd:cd08591    1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 394 IRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLD------GVttSLPSPEQlkgkillkgkklggll 467
Cdd:cd08591   81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEkyplepGV--PLPSPND---------------- 142

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 468 ppggeggpeatvvsdedeaaeiedeavrsrVQRKPredklrLV--KELSDMVIYCKSVHFGGFSspgtpgQA-----FYE 540
Cdd:cd08591  143 ------------------------------LKRKI------LIknKKLSSLVNYIQPVKFQGFE------VAekrnkHYE 180

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 823429468 541 MVSFSENRALRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08591  181 MSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257

PI-PLCc

cd00137

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...

316-617

7.01e-97

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: 302.65 E-value: 7.01e-97

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLT-----GPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTsKILLCDV 390
Cdd:cd00137    1 HHPDTQPLAHYSIPGTHDTYLTAGQFTikqvwGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 391 LRAIRDYAFKASPYPVILSLENHCSL--EQQRVMARHLRTILGPMLLDrPLDGVTTSLPSPEQlkgkillkgkklggllp 468
Cdd:cd00137   80 IEAIAQFLKKNPPETIIMSLKNEVDSmdSFQAKMAEYCRTIFGDMLLT-PPLKPTVPLPSLED----------------- 141

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 469 pggeggpeatvvsdedeaaeiedeaVRSRVQRKPREDklrlvkELSDMVIYCKSvHFGGFSSPGTPGQAFYEMVSFSENR 548
Cdd:cd00137  142 -------------------------LRGKILLLNKKN------GFSGPTGSSND-TGFVSFEFSTQKNRSYNISSQDEYK 189

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 549 ALR----LLQESGNNLVRHNVSHLSRIYPAGWR---------TDSSNYSPVEMWNG---GCQIVALNFQTPGPEMDVYQG 612
Cdd:cd00137  190 AYDdekvKLIKATVQFVDYNKNQLSRNYPSGTSggtawyyyaMDSNNYMPQMFWNAnpaGCGIVILDFQTMDLPMQQYMA 269


                 ....*
gi 823429468 613 RFQDN 617
Cdd:cd00137  270 VIEFN 274

PI-PLCc_gamma

cd08592

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...

317-617

1.46e-95

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: 297.42 E-value: 1.46e-95

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 317 QDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIRD 396
Cdd:cd08592    2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 397 YAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQlkgkillkgkklggllppggeggpe 476
Cdd:cd08592   82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQ------------------------- 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 477 atvvsdedeaaeiedeavrsrVQRKpredklrlvkelsdMVIYCKSVhfggfsspgtpgqaFYEMVSFSENRALRLL-QE 555
Cdd:cd08592  137 ---------------------LKRK--------------IIIKHKKL--------------FYEMSSFPETKAEKYLnRQ 167

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 823429468 556 SGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08592  168 KGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFMLN 229

PI-PLC1c_yeast

cd08598

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...

316-617

4.89e-92

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: 288.38 E-value: 4.89e-92

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08598    1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQlkgkillkgkklggllppggeggp 475
Cdd:cd08598   81 KYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDGLEDELPSPEE------------------------ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 476 eatvvsdedeaaeiedeaVRSRVqrkpredklrLVKelsdmviyCKSVhfggfSSPgtpgqaFYEMVSFSENRALRLLQE 555
Cdd:cd08598  137 ------------------LRGKI----------LIK--------VKKE-----SKT------PNHIFSLSERSLLKLLKD 169

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 823429468 556 SGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08598  170 KRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMFAGS 231

PI-PLCc_beta4

cd08626

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...

316-617

1.64e-83

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: 267.02 E-value: 1.64e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGP--NQEPIIYHGYTFTSKILLCDVLRA 393
Cdd:cd08626    1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 394 IRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTT----SLPSPEQlkgkillkgkklggllpp 469
Cdd:cd08626   81 IKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLESHPLepgvPLPSPNK------------------ 142

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 470 ggeggpeatvvsdedeaaeiedeavrsrVQRKpredKLRLVKELSDMVIYCKSVHFGGFSSpGTPGQAFYEMVSFSENRA 549
Cdd:cd08626  143 ----------------------------LKRK----ILIKNKRLSSLVNYAQPVKFQGFDV-AEERNIHFNMSSFNESVG 189

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 823429468 550 LRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08626  190 LGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257

EFh_PI-PLCdelta1

cd16217

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...

165-304

2.74e-83

Pssm-ID: 320047 [Multi-domain] Cd Length: 139 Bit Score: 261.60 E-value: 2.74e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKMLTQREEIDRTFAEAAG 244
Cdd:cd16217    1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSKSGFLEGEEIEEFYKLLTKREEIDVIFGEYAK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 245 SREMLSVDQLVTFLQHQQREEaAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16217   81 SDGTMSRNNLLNFLQEEQREE-VAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139

PI-PLCc_gamma2

cd08628

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...

317-617

4.86e-83

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: 265.77 E-value: 4.86e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 317 QDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIRD 396
Cdd:cd08628    2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 397 YAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQlkgkillkgkklggllppggeggpe 476
Cdd:cd08628   82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEASADQLPSPTQ------------------------- 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 477 atvvsdedeaaeiedeaVRSRVQRKPRedKLrLVKELSDMVIYCK--SVHFGGFSSPgtpgqAFYEMVSFSENRALRLLQ 554
Cdd:cd08628  137 -----------------LKEKIIIKHK--KL-IAIELSDLVVYCKptSKTKDNLENP-----DFKEIRSFVETKAPSIIR 191

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 823429468 555 ESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08628  192 QKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFSLN 254

PI-PLC-X

pfam00388

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...

319-451

7.34e-82

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: 7.34e-82

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  319 MGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIRDYA 398
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 823429468  399 FKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQ 451
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPED 133

PI-PLCc_eta

cd08594

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...

316-617

3.43e-79

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: 254.34 E-value: 3.43e-79

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08594    1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPML-LDRPLDGVTTSLPSPEqlkgkillkgkklggllppggegg 474
Cdd:cd08594   81 KYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLdLSSVISGDSKQLPSPQ------------------------ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 475 peatvvsdedeaaeiedeAVRSRVqrkpredklrLVKelsdmviycksvhfggfsspGTPGQafyeMVSFSENRALRLLQ 554
Cdd:cd08594  137 ------------------SLKGKI----------LIK--------------------GKKWQ----VSSFSETRAHQIVQ 164

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 823429468 555 ESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08594  165 QKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227

PI-PLCc_eta2

cd08633

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...

317-617

3.59e-79

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: 255.35 E-value: 3.59e-79

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 317 QDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIRD 396
Cdd:cd08633    2 QDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 397 YAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPML-LDRPLDGVTTSLPSPEqlkgkillkgkklggllppggeggp 475
Cdd:cd08633   82 YAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLdLSSVISNDCTRLPSPE------------------------- 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 476 eatvvsdedeaaeiedeAVRSRVQRKPRedklRLVKELSDMVIYCKSVhfgGFSSPGTPGQAFYEMVSFSENRALRLLQE 555
Cdd:cd08633  137 -----------------ILKGKILVKGK----KLSRALSDLVKYTKSV---RVHDIETEATSSWQVSSFSETKAHQILQQ 192

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 823429468 556 SGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08633  193 KPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254

PI-PLCc_eta1

cd08632

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...

316-617

4.99e-79

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: 254.95 E-value: 4.99e-79

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08632    1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPML-LDRPLDGVTTSLPSPEqlkgkillkgkklggllppggegg 474
Cdd:cd08632   81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLdLSSVLTGDPKQLPSPQ------------------------ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 475 peatvvsdedeaaeiedeAVRSRVQRKPRedklRLVKELSDMVIYCKSVHFGGFSSPGTPGQafyeMVSFSENRALRLLQ 554
Cdd:cd08632  137 ------------------LLKGKILVKGK----KLCRDLSDLVVYTNSVAAQDIVDDGSTGN----VLSFSETRAHQLVQ 190

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 823429468 555 ESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08632  191 QKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253

PI-PLCc_epsilon

cd08596

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...

317-617

8.17e-79

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: 254.39 E-value: 8.17e-79

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 317 QDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIRD 396
Cdd:cd08596    2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 397 YAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPL---DGVTT-SLPSPEQlkgkillkgkklggllppgge 472
Cdd:cd08596   82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLfesDFSDDpSLPSPLQ--------------------- 140

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 473 ggpeatvvsdedeaaeiedeaVRSRVQRKPREdklrlVKELSDMVIYCKSVHFGGFSSPGTpgqafYEMVSFSENRALRL 552
Cdd:cd08596  141 ---------------------LKNKILLKNKK-----APELSDLVIYCQAVKFPGLSTPKC-----YHISSLNENAAKRL 189

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 823429468 553 LQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08596  190 CRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254

PLN02228

Phosphoinositide phospholipase C

233-806

9.33e-78

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 261.89 E-value: 9.33e-78

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 233 EEIDRTFaEAAGSREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSADGSAFSLAh 312
Cdd:PLN02228  24 VSIKRLF-EAYSRNGKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSDTNSPLPMS- 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 313 RRVYQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPN-QEPIIYHGYTFTSKILLCDVL 391
Cdd:PLN02228 102 GQVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSgNAAEVRHGRTLTSHEDLQKCL 181

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 392 RAIRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLdRPLDGVTTSLPSPEQLKGKILLKGKKLGGLLPPGG 471
Cdd:PLN02228 182 NAIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLF-RCTSESTKHFPSPEELKNKILISTKPPKEYLESKT 260

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 472 EggpEATVVSDEDEAAEIEDEAVRSRVQRKPREDKLRLVkELSDMViyckSVHFGGFSSP------GTPGQAFyeMVSFS 545
Cdd:PLN02228 261 V---QTTRTPTVKETSWKRVADAENKILEEYKDEESEAV-GYRDLI----AIHAANCKDPlkdclsDDPEKPI--RVSMD 330

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 546 ENRALRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDNGACGYVLK 625
Cdd:PLN02228 331 EQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKK 410

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 626 PAFLRDPNSTFNSraLAQGPwwTRKRLSVRVrpaTTGTGAHgppspLPFLNPHLsfaptqvisgqqlpkvnkNKNSIVDP 705
Cdd:PLN02228 411 PRILLDEHTLFDP--CKRLP--IKTTLKVKI---YTGEGWD-----LDFHLTHF------------------DQYSPPDF 460

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 706 KVTVEIHGVGRDVASCQTAVVTNNGFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKNDFIGQSTIPLGSLKQGYRHVH 785
Cdd:PLN02228 461 FVKIGIAGVPRDTVSYRTETAVDQWFPIWGNDEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRAVR 540

                        570       580
                 ....*....|....*....|.
gi 823429468 786 LLSKNGDQHPSATLFVKVSLQ 806
Cdd:PLN02228 541 LHDRAGKAYKNTRLLVSFALD 561

PI-PLCc_gamma1

cd08627

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...

317-617

2.26e-74

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: 241.86 E-value: 2.26e-74

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 317 QDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIRD 396
Cdd:cd08627    2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 397 YAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQlkgkillkgkklggllppggeggpe 476
Cdd:cd08627   82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPVDINADGLPSPNQ------------------------- 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 477 atvvsdedeaaeiedeavrsrVQRKpredklrlvkelsdMVIYCKSVhfggfsspgtpgqaFYEMVSFSENRALRLLQES 556
Cdd:cd08627  137 ---------------------LKRK--------------ILIKHKKL--------------YRDMSSFPETKAEKYVNRS 167

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 823429468 557 -GNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08627  168 kGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMLG 229

PI-PLCc_beta2

cd08624

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...

316-617

5.71e-72

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: 236.49 E-value: 5.71e-72

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDG--PNQEPIIYHGYTFTSKILLCDVLRA 393
Cdd:cd08624    1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 394 IRDYAFKASPYPVILSLENHC-SLEQQRVMARHLRTILGPMLLDRPLD------GVttSLPSPEQlkgkillkgkklggl 466
Cdd:cd08624   81 IAESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLTEPLEkyplkpGV--PLPSPED--------------- 143

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 467 lppggeggpeatvvsdedeaaeiedeaVRSRVQRKPREdklrlVKELSDMVIYCKSVHFGGFSSPGTPGQAfYEMVSFSE 546
Cdd:cd08624  144 ---------------------------LRGKILIKNKK-----YEEMSSLVNYIQPTKFVSFEFSAQKNRS-YVISSFTE 190

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 823429468 547 NRALRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08624  191 LKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLPMQQNMALFEFN 261

PLCXc

smart00148

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...

319-451

5.93e-72

Pssm-ID: 197543 [Multi-domain] Cd Length: 143 Bit Score: 231.79 E-value: 5.93e-72

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468   319 MGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIRDYA 398
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 823429468   399 FKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQ 451
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQ 133

PI-PLCc_beta3

cd08625

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...

318-617

8.11e-72

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: 236.10 E-value: 8.11e-72

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 318 DMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDG--PNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08625    3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHC-SLEQQRVMARHLRTILGPMLLDRPLD------GVttSLPSPEQlkgkillkgkklggllp 468
Cdd:cd08625   83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDkyplvpGV--QLPSPQE----------------- 143

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 469 pggeggpeatvvsdedeaaeiedeaVRSRVQRKPredklrlvKELSDMVIYCKSVHFGGFSSpGTPGQAFYEMVSFSENR 548
Cdd:cd08625  144 -------------------------LMGKILVKN--------KKMSTLVNYIEPVKFKSFEA-AAKRNKFFEMSSFVETK 189

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 823429468 549 ALRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08625  190 AMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258

PLN02952

phosphoinositide phospholipase C

233-802

2.76e-69

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 239.90 E-value: 2.76e-69

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 233 EEIDRTFAEAAGSREMLSVDQLVTFLQHQQREEAAGPALALSLIEryepsETAKAQRQMTK--------DGFLMYLLSAD 304
Cdd:PLN02952  38 DDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVE-----EVINRRHHVTRytrhglnlDDFFHFLLYDD 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 305 GSAFSLAHrrVYQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPI-IYHGYTFTS 383
Cdd:PLN02952 113 LNGPITPQ--VHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEIlVLHGRTLTT 190

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 384 KILLCDVLRAIRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTtSLPSP-------------- 449
Cdd:PLN02952 191 PVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYPESDSLV-QFPSPeslkhriiistkpp 269

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 450 ----EQLKGKILLKGKKLGGLLPPGGEGGPEATVVSDEDEAAEIEDEAVRSRVQRKPREDKLRLVKELSdmviyckSVHF 525
Cdd:PLN02952 270 keylESSGPIVIKKKNNVSPSGRNSSEETEEAQTLESMLFEQEADSRSDSDQDDNKSGELQKPAYKRLI-------TIHA 342

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 526 GgfSSPGTPGQAFYEMV------SFSENRALRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALN 599
Cdd:PLN02952 343 G--KPKGTLKDAMKVAVdkvrrlSLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFN 420

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 600 FQTPGPEMDVYQGRFQDNGACGYVLKPAFLRDP---NSTFNSRALAQgpwwTRKRLSVRVrpaTTGTGAHgppspLPFLN 676
Cdd:PLN02952 421 MQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDEVFDPKKKLP----VKKTLKVKV---YLGDGWR-----LDFSH 488

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 677 PHL-SFAPTqvisgqqlpkvnknknsivDPKVTVEIHGVGRDVASCQTAVVTNNgFNPWWDTEFVFEVVVPELALVRFLV 755
Cdd:PLN02952 489 THFdSYSPP-------------------DFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEV 548

                        570       580       590       600
                 ....*....|....*....|....*....|....*....|....*..
gi 823429468 756 EDYDASSKNDFIGQSTIPLGSLKQGYRHVHLLSKNGDQHPSATLFVK 802
Cdd:PLN02952 549 REYDMSEKDDFGGQTCLPVSELRPGIRSVPLHDKKGEKLKNVRLLMR 595

PH_PLC_delta

cd13363

Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...

43-160

3.75e-68

Pssm-ID: 270169 Cd Length: 117 Bit Score: 220.65 E-value: 3.75e-68

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  43 LLKGSQLLKVKSNSWRRERFYKLQEDCKTIWQESRKvMRTPESQLFSIEDIQEVRKGHRTEGMEKFARDVPEDRCFSIVF 122
Cdd:cd13363    1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKK-TRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVF 79

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 823429468 123 KDQRNTLDLIAPSPAEAQHWVQGLRKIIHHSGSMDQRQ 160
Cdd:cd13363   80 KGRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117

PLN02222

phosphoinositide phospholipase C 2

237-805

2.79e-65

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 228.38 E-value: 2.79e-65

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 237 RTFAEAAGSREMLSVDQLVTFLQHQQREEAAGPALALSLIEryePSETAKAQRQMTKDGFLMYLLSADGSAFSLahRRVY 316
Cdd:PLN02222  28 KTIFEKYSENGVMTVDHLHRFLIDVQKQDKATREDAQSIIN---SASSLLHRNGLHLDAFFKYLFGDNNPPLAL--HEVH 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 317 QDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPI-IYHGYTFTSKILLCDVLRAIR 395
Cdd:PLN02222 103 HDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKCLKAIR 182

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPeqlkgkilLKGKKLGGLLPPGGEGGP 475
Cdd:PLN02222 183 AHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFTPPVGESLKEFPSP--------NSLKKRIIISTKPPKEYK 254

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 476 EATVVSDEDEAAEIEDEAVRSR-----VQRKPRED-------------------KLRLVKELSDMVIYCKSVHFGGFSSP 531
Cdd:PLN02222 255 EGKDDEVVQKGKDLGDEEVWGRevpsfIQRNKSVDkndsngddddddddgedksKKNAPPQYKHLIAIHAGKPKGGITEC 334

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 532 GTPGQAFYEMVSFSENRALRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQ 611
Cdd:PLN02222 335 LKVDPDKVRRLSLSEEQLEKAAEKYAKQIVRFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQ 414

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 612 GRFQDNGACGYVLKPAFLRDPNST---FNSRALAqgPWWTRKRLSVRVrpattGTGAHgppsplpFLNPHLSFaptqvis 688
Cdd:PLN02222 415 GMFRANGGCGYIKKPDLLLKSGSDsdiFDPKATL--PVKTTLRVTIYM-----GEGWY-------FDFRHTHF------- 473

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 689 gqqlpkvnkNKNSIVDPKVTVEIHGVGRDVASCQTAVVTNNgFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKNDFIG 768
Cdd:PLN02222 474 ---------DQYSPPDFYTRVGIAGVPGDTVMKKTKTLEDN-WIPAWDEVFEFPLTVPELALLRLEVHEYDMSEKDDFGG 543

                        570       580       590
                 ....*....|....*....|....*....|....*..
gi 823429468 769 QSTIPLGSLKQGYRHVHLLSKNGDQHPSATLFVKVSL 805
Cdd:PLN02222 544 QTCLPVWELSQGIRAFPLHSRKGEKYKSVKLLVKVEF 580

PI-PLCc_beta1

cd08623

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...

317-617

7.03e-62

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: 209.17 E-value: 7.03e-62

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 317 QDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDG--PNQEPIIYHGYTFTSKILLCDVLRAI 394
Cdd:cd08623    2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 395 RDYAFKASPYPVILSLENHC-SLEQQRVMARHLRTILGPMLLDRPLD------GVttSLPSPEQlkgkillkgkklggll 467
Cdd:cd08623   82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEkyplesGV--PLPSPMD---------------- 143

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 468 ppggeggpeatvvsdedeaaeiedeaVRSRVQRKPredklrlvKELSDMVIYCKSVHFGGFSSPGTPGQAfYEMVSFSEN 547
Cdd:cd08623  144 --------------------------LMYKILVKN--------KKMSNLVNYIQPVKFESFEASKKRNKS-FEMSSFVET 188

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 548 RALRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08623  189 KGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 258

PI-PLC-Y

pfam00387

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...

513-628

1.40e-61

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

Pssm-ID: 459794 Cd Length: 114 Bit Score: 202.69 E-value: 1.40e-61

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  513 LSDMVIYCKSVHFGGFSSPGTpgQAFYEMVSFSENRALRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGG 592
Cdd:pfam00387   1 LSDLVVYTQSVKFKSFSTPES--KTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCG 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 823429468  593 CQIVALNFQTPGPEMDVYQGRFQDNGACGYVLKPAF 628
Cdd:pfam00387  79 VQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114

PLCYc

smart00149

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...

514-629

3.96e-60

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: 199.00 E-value: 3.96e-60

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468   514 SDMVIYCKSVHFGGFSSPgTPGQAFYEMVSFSENRALRLLQESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGC 593
Cdd:smart00149   1 SDLVIYCAPVKFRSFESA-ESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGC 79

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 823429468   594 QIVALNFQTPGPEMDVYQGRFQDNGACGYVLKPAFL 629
Cdd:smart00149  80 QMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PI-PLCc_plant

cd08599

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...

316-617

2.13e-59

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: 201.06 E-value: 2.13e-59

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAIR 395
Cdd:cd08599    1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 396 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQlkgkillkgkklggllppggeggp 475
Cdd:cd08599   81 ENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPDSEDLPEEFPSPEE------------------------ 136

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 476 eatvvsdedeaaeiedeaVRSRV--QRKPRedklrlvkelsdmviycksvhfggfsspgtpgqafYEMVSFSEnRALRLL 553
Cdd:cd08599  137 ------------------LKGKIliSDKPP-----------------------------------VIRNSLSE-TQLKKV 162

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 823429468 554 --QESGNNLVRHNVSHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDN 617
Cdd:cd08599  163 ieGEHPTDLIEFTQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKFRAN 228

EFh_PI-PLCdelta

cd16202

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...

165-304

6.78e-58

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta 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 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 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. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.

Pssm-ID: 320032 [Multi-domain] Cd Length: 140 Bit Score: 193.60 E-value: 6.78e-58

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKMLTQREEIDRTFAEAAG 244
Cdd:cd16202    1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQFYNRLTKRPEIEELFKKYSG 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 245 SREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16202   81 DDEALTVEELRRFLQEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSPD 140

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

685-806

3.21e-54

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 183.13 E-value: 3.21e-54

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 685 QVISGQQLPKVNKNKNSIVDPKVTVEIHGVGRDV-ASCQTAVVTNNGFNPWWDTEFVFEVVVPELALVRFLVEDYDaSSK 763
Cdd:cd00275    7 KIISGQQLPKPKGDKGSIVDPYVEVEIHGLPADDsAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYDED-SGD 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 823429468 764 NDFIGQSTIPLGSLKQGYRHVHLLSKNGDQHPSATLFVKVSLQ 806
Cdd:cd00275   86 DDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

PLN02230

phosphoinositide phospholipase C 4

288-802

5.41e-48

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 179.90 E-value: 5.41e-48

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 288 QRQMTKDGFLMYLLSADGSafSLAHRRVYQDMGQPLSHYLMSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCVELDCWD 367
Cdd:PLN02230  88 RRNLTLDDFNYYLFSTDLN--PPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWP 165

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 368 GPNQEPIIYHGYTFTSKILLCDVLRAIRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVtTSLP 447
Cdd:PLN02230 166 RGTDDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYHDSEGC-QEFP 244

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 448 SPEQLKGKILLKGKKLGGLLPPGGEGGPEATVVSDEDE------------AAEIEDEAVRSRVQRKPREDKLRLVKElSD 515
Cdd:PLN02230 245 SPEELKEKILISTKPPKEYLEANDAKEKDNGEKGKDSDedvwgkepedliSTQSDLDKVTSSVNDLNQDDEERGSCE-SD 323

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 516 MVIYCKSVHFGGFSS--PGTPGQAFYEMVSFSENRALRL-LQES---------GNNLVRHNVSHLSRIYPAGWRTDSSNY 583
Cdd:PLN02230 324 TSCQLQAPEYKRLIAihAGKPKGGLRMALKVDPNKIRRLsLSEQllekavasyGADVIRFTQKNFLRIYPKGTRFNSSNY 403

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 584 SPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDNGACGYVLKPAFLRDPNSTfnsralAQGPW-----WTRKRLSVRVrp 658
Cdd:PLN02230 404 KPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDFLMDAGPN------GQDFYpkdnsCPKKTLKVKV-- 475

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 659 attgtgAHGPPSPLPFLNPHL-SFAPTqvisgqqlpkvnknknsivDPKVTVEIHGVGRDVASCQTAVVTNNgFNPWWDT 737
Cdd:PLN02230 476 ------CMGDGWLLDFKKTHFdSYSPP-------------------DFFVRVGIAGAPVDEVMEKTKIEYDT-WTPIWNK 529

                        490       500       510       520       530       540
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 823429468 738 EFVFEVVVPELALVRFLVEDYDASSKNDFIGQSTIPLGSLKQGYRHVHLLSKNGDQHPSATLFVK 802
Cdd:PLN02230 530 EFIFPLAVPELALLRVEVHEHDINEKDDFGGQTCLPVSEIRQGIHAVPLFNRKGVKYSSTRLLMR 594

EF-hand_like

pfam09279

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...

225-309

1.32e-46

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 160.49 E-value: 1.32e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  225 FYKMLTQREEIDRTFAEAAGSREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:pfam09279   1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                  ....*
gi 823429468  305 GSAFS 309
Cdd:pfam09279  81 GSIFN 85

EFh_PI-PLCdelta4

cd16219

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...

165-304

1.46e-42

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (PLCD4), or phospholipase C-delta-4 (PLC-delta-4), is expressed in various tissues with the highest levels detected selectively in the brain, skeletal muscle, testis and kidney. It plays a significant role in cell growth, cell proliferation, tumorigenesis, and in an early stage of fertilization. PI-PLC-delta4 may function as a key enzyme in the regulation of PtdIns(4,5)P2 levels and Ca2+ metabolism in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+. Moreover, PI-PLC-delta4 binds glutamate receptor-interacting protein1 (GRIP1) in testis and is required for calcium mobilization essential for the zona pellucida-induced acrosome reaction in sperm. Overexpression or dysregulated expression of PLCdelta4 may initiate oncogenesis in certain tissues through upregulating erbB1/2 expression, extracellular signal-regulated kinase (ERK) signaling pathway, and proliferation in MCF-7 cells. PI-PLC-delta4 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, 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. 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.

Pssm-ID: 320049 [Multi-domain] Cd Length: 140 Bit Score: 151.15 E-value: 1.46e-42

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKMLTQREEIDRTFAEAAG 244
Cdd:cd16219    1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSESGTLEGEEFVLFYKALTQREDVLKIFQDFSA 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 245 SREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16219   81 DGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140

EFh_PI-PLCdelta3

cd16218

EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...

165-304

6.29e-41

EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 (PLCD3), phospholipase C-delta-3 (PLC-delta-3), is expressed abundantly in brain, skeletal muscle and heart. PI-PLC-delta3 gene expression is down-regulation by cAMP and calcium. PI-PLC-delta3 acts as anchoring of myosin VI on plasma membrane, and further modulates Myosin IV expression and microvilli formation in enterocytes. It negatively regulates RhoA expression, inhibits RhoA/Rho kinase signaling, and plays an essential role in normal neuronal migration by promoting neuronal outgrowth in the developing brain. Moreover, PI-PLC-delta3 is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta3 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta3 contains 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 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. In addition, PI-PLC-delta3 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, which may be responsible transporting PI-PLC-delta3 from the cell nucleus.

Pssm-ID: 320048 [Multi-domain] Cd Length: 138 Bit Score: 146.43 E-value: 6.29e-41

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKMLTQREEIDRTFAEAAG 244
Cdd:cd16218    1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRSNDDRLEEHEIEEFCRRLMQRPELEEIFHQYSG 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 245 SREMLSVDQLVTFLqHQQREEAAgPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16218   81 EDCVLSAEELREFL-KDQGEDAS-LVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138

EFh_PI-PLC

cd15898

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...

165-304

8.37e-38

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.

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 137.80 E-value: 8.37e-38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKMLTQREEIDRTFAEAAG 244
Cdd:cd15898    1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTERPELEPIFKKYAG 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 823429468 245 S-REMLSVDQLVTFLQHQQREEAAgPALALSLIERYEPSETakaQRQMTKDGFLMYLLSAD 304
Cdd:cd15898   81 TnRDYMTLEEFIRFLREEQGENVS-EEECEELIEKYEPERE---NRQLSFEGFTNFLLSPE 137

PH_PLC_ELMO1

cd01248

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...

43-150

8.34e-37

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The C-terminal region of ELMO1, the PH domain and Pro-rich sequences, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle allowing for DOCK mediated Rac1 activation. ELMO1, a mammalian homolog of C. elegans CED-12, contains an N-terminal RhoG-binding region, a ELMO domain, a PH domain, and a C-terminal sequence with three PxxP motifs. 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 which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). All PLCs, except for PLCzeta, have a PH domain which is for most part N-terminally located, though lipid binding specificity is not conserved between them. In addition PLC gamma contains a split PH domain within its catalytic domain that is separated by 2 SH2 domains and a single SH3 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: 269952 Cd Length: 108 Bit Score: 133.60 E-value: 8.34e-37

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  43 LLKGSQLLKVKSNSWRRERFYKLQEDCKTIWQESRKVMrtPESQLFSIEDIQEVRKGHRTEGMEKF--ARDVPEDRCFSI 120
Cdd:cd01248    1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKK--SEKKSIDISDIKEIRPGKDTDGFKRKkkSNKPKEERCFSI 78

                         90       100       110
                 ....*....|....*....|....*....|
gi 823429468 121 VFKDQRNTLDLIAPSPAEAQHWVQGLRKII 150
Cdd:cd01248   79 IYGSNNKTLDLVAPSEDEANLWVEGLRALL 108

PLN02223

phosphoinositide phospholipase C

316-802

2.53e-32

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 132.45 E-value: 2.53e-32

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 316 YQDMGQPLSHYLMSSSHNTYLLEDQLTGPS-STEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFTSKILLCDVLRAI 394
Cdd:PLN02223 105 HHDMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLLPDGKDGICVRPKWNFEKPLELQECLDAI 184

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 395 RDYAF-KASPYPVILSLENHCSLEQQRVMARHLRTILGPMLLDRPLDGVTTSLPSPEQLkGKILLKGKKLGGLLPPGGEG 473
Cdd:PLN02223 185 KEHAFtKCRSYPLIITFKDGLKPDLQSKATQMIDQTFGDMVYHEDPQHSLEEFPSPAEL-QNKILISRRPPKELLYAKAD 263

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 474 GPEATVVSDEDEAAEIEDEAVRSRVQRKPREDKLRLVKELSdmviycksvhfGGFSSPGTPGQAFYEMVSFSENRALRLL 553
Cdd:PLN02223 264 DGGVGVRNELEIQEGPADKNYQSLVGFHAVEPRGMLQKALT-----------GKADDIQQPGWYERDIISFTQKKFLRTR 332

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 554 QESGNNLvrhnvshlsrIYPAgwrtdssnYSPVEMWNGGCQIVALNFQTPGPEMDVYQGRFQDNGACGYVLKPAFLRDPN 633
Cdd:PLN02223 333 PKKKNLL----------INAP--------YKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNAG 394

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 634 STfnsralaqGPWWtrkrlsvrvrpattgtgahgppsplPFLNPhlsfaptqVISGQQLPKVNKNKNSIVDPK------- 706
Cdd:PLN02223 395 PS--------GVFY-------------------------PTENP--------VVVKILKVKIYMGDGWIVDFKkrigrls 433

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 707 -----VTVEIHGVGRDVASCQTaVVTNNGFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKNDFIGQSTIPLGSLKQGY 781
Cdd:PLN02223 434 kpdlyVRISIAGVPHDEKIMKT-TVKNNEWKPTWGEEFTFPLTYPDLALISFEVYDYEVSTADAFCGQTCLPVSELIEGI 512

                        490       500
                 ....*....|....*....|.
gi 823429468 782 RHVHLLSKNGDQHPSATLFVK 802
Cdd:PLN02223 513 RAVPLYDERGKACSSTMLLTR 533

PI-PLCc_GDPD_SF

cd08555

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...

330-437

5.26e-28

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: 111.37 E-value: 5.26e-28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 330 SSHNTYLLEDQltgPSSTEAYIRALCKGCRCVELDCWDGPNQEPIIYHGYTFT------SKILLCDVLRAIRDYAFkASP 403
Cdd:cd08555    2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 823429468 404 YPVILSLENHCS----LEQQRVMARHLRTILGPMLLDR 437
Cdd:cd08555   78 YTIILSLEIKQDspeyDEFLAKVLKELRVYFDYDLRGK 115

PH_PLC_eta

cd13364

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...

45-150

5.66e-24

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of two enzymes, PLCeta1 and PLCeta2. They hydrolyze phosphatidylinositol 4,5-bisphosphate, are more sensitive to Ca2+ than other PLC isozymes, and involved in PKC activation in the brain and neuroendocrine systems. PLC-eta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves by a variable linker, a C2 domain, and a C-terminal PDZ domain. 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.involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. 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 kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.

Pssm-ID: 270170 Cd Length: 109 Bit Score: 97.35 E-value: 5.66e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  45 KGSQLLKVKSNSWRRERFYKLQEDCKTI-WQESRKvmrTPESQLFSIEDIQEVRKGHRTEGMEK--FARDVPEDRCFSIV 121
Cdd:cd13364    3 EGSELVKVRSNSRQYRRFFYLDEDKSSIrWKPSKK---KSEKAKIPISSIREVREGKTTDIFRScdISGDFPEECCFSII 79

                         90       100
                 ....*....|....*....|....*....
gi 823429468 122 FKDQRNTLDLIAPSPAEAQHWVQGLRKII 150
Cdd:cd13364   80 YGEEYETLDLVASSPDEANIWITGLRYLM 108

EF-hand_10

pfam14788

EF hand;

180-229

4.19e-23

EF hand;

Pssm-ID: 405477 Cd Length: 50 Bit Score: 92.48 E-value: 4.19e-23

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 823429468  180 KMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKML 229
Cdd:pfam14788   1 KMSFKELKNFLRLINIEVDDSYARKLFQKCDTSQSGRLEGEEIEEFYKLL 50

EFh_PI-PLCeta

cd16205

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...

165-304

9.03e-23

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, 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. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.

Pssm-ID: 320035 [Multi-domain] Cd Length: 141 Bit Score: 94.76 E-value: 9.03e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTD-SLEDDEIEAFYKMLTQREEIDRTFAEAA 243
Cdd:cd16205    1 WLKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNQgTLDFEEFCAFYKMMSTRRELYLLLLSYS 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 823429468 244 GSREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16205   81 NKKDYLTLEDLARFLEVEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

686-786

2.91e-22

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 92.17 E-value: 2.91e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468   686 VISGQQLPKvnKNKNSIVDPKVTVEIHGVGRDVAscQTAVVTNNGfNPWWDTEFVFEVVVPELALVRFLVEDYDASSKND 765
Cdd:smart00239   6 IISARNLPP--KDKGGKSDPYVKVSLDGDPKEKK--KTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                           90       100
                   ....*....|....*....|.
gi 823429468   766 FIGQSTIPLGSLKQGYRHVHL 786
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRHEKL 101

EFh_PI-PLCzeta

cd16204

EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...

174-304

7.16e-19

EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1, or phospholipase C-zeta-1 (PLC-zeta-1), or testis-development protein NYD-SP27, is only found in the testis. The sperm-specific PI-PLC 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. PI-PLC-zeta1 contains an N-terminal four atypical EF-hand motifs, 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. Unlike other PI-PLCs, PI-PLC-zeta is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. There is only one PLC-zeta isozyme. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.

Pssm-ID: 320034 [Multi-domain] Cd Length: 142 Bit Score: 83.71 E-value: 7.16e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 174 DKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKMLTQREEIDRTFAEAAGSREMLSVDQ 253
Cdd:cd16204   12 DRFRKGKINLESTLKLLEKLDIPFDYIHVKYIFKKNDSFKAGNITIEDFRAIYRAIAHRCEIHEIFNTYSENRKILSAPN 91

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 823429468 254 LVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16204   92 LVGFLKKEQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTSED 142

pfam00168

C2 domain;

686-785

7.34e-19

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 82.37 E-value: 7.34e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  686 VISGQQLPkvNKNKNSIVDPKVTVEIHgvgRDVASCQTAVVtNNGFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKND 765
Cdd:pfam00168   7 VIEAKNLP--PKDGNGTSDPYVKVYLL---DGKQKKKTKVV-KNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80

                          90       100
                  ....*....|....*....|
gi 823429468  766 FIGQSTIPLGSLKQGYRHVH 785
Cdd:pfam00168  81 FIGEVRIPLSELDSGEGLDG 100

EFh_PRIP

cd16206

EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...

165-304

8.66e-18

EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); This family represents a class of 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, four atypical EF-hand motifs, 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(also known as p130 or PLC-L1), which is predominantly expressed in the brain, and PRIP-2 (also known as PLC-L2), 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: 320036 [Multi-domain] Cd Length: 143 Bit Score: 80.72 E-value: 8.66e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTD---SLEDDEIEAFYKMLTQREEIDRTFAE 241
Cdd:cd16206    1 WLESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTSRIKQKLKELQKKKDGargRVSSDEFVELFKELATRPEIYFLLVR 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 823429468 242 AAGSREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16206   81 YASNKDYLTVDDLMLFLEAEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSEE 143

EFh_ScPlc1p_like

cd16207

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...

163-304

1.35e-17

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar proteins; This family represents 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 family is protein Plc1p (also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1) encoded by PLC1 genes from Saccharomyces cerevisiae. ScPlc1p 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 ScPlc1p 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 SCPlc1p, 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: 320037 [Multi-domain] Cd Length: 142 Bit Score: 79.99 E-value: 1.35e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 163 QHWihsclRKADKNK---DNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKMLTQREEIDRTF 239
Cdd:cd16207    3 IHW-----KRADSKKqdgDERLDFEDVEKLCRRLHINCSESYLRELFDKADTDKKGYLNFEEFQEFVKLLKRRKDIKAIF 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 823429468 240 AEAAGSREM-LSVDQLVTFLQHQQREEAAgPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16207   78 KQLTKPGSDgLTLEEFLKFLRDVQKEDVD-RETWEKIFEKFARRIDDSDSLTMTLEGFTSFLLSSY 142

EFh_PI-PLC21

cd16213

EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...

225-304

5.36e-16

EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family includes invertebrate homologs of phosphoinositide phospholipase C beta (PI-PLC-beta) named PLC21 from cephalopod retina. It also includes PLC21 encoded by plc-21 gene, which is expressed in the central nervous system of Drosophila. Like beta-class of vertebrate PI-PLCs, PLC21 contains 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.

Pssm-ID: 320043 Cd Length: 154 Bit Score: 75.80 E-value: 5.36e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 225 FYKMLTQREEIDRTFAE-AAGSREMLSVDQLVTFLQHQQREEA--------AGPALALSLIERYEPSETAKAQRQMTKDG 295
Cdd:cd16213   66 FYRRLTGRQEVEKIFDElGAKKKPYLTTEQFVDFLNKTQRDPRlneilypyANPKRARDLINQYEPNKSFAKKGHLSVEG 145


                 ....*....
gi 823429468 296 FLMYLLSAD 304
Cdd:cd16213  146 FLRYLMSED 154

EFh_PI-PLCeta2

cd16221

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...

165-302

2.85e-15

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also 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. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, 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. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.

Pssm-ID: 320051 [Multi-domain] Cd Length: 141 Bit Score: 73.43 E-value: 2.85e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECD-NSQTDSLEDDEIEAFYKMLTQREEIDRTFAEAA 243
Cdd:cd16221    1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADtDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 823429468 244 GSREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLS 302
Cdd:cd16221   81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRS 139

EFh_PI-PLCeta1

cd16220

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...

165-302

4.72e-15

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, or phospholipase C-eta-1 (PLC-eta-1), or phospholipase C-like protein 3 (PLC-L3), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the zona incerta and in the spinal cord. PI-PLC-eta1 may perform a fundamental role in the brain. It may also act in synergy with other PLC subtypes. For instance, it is activated via intracellular Ca2+ mobilization and then plays a role in the amplification of GPCR (G-protein-coupled receptor)-mediated PLC-beta signals. In addition, its activity can be stimulated by ionomycin. PI-PLC-eta1 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, 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. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.

Pssm-ID: 320050 [Multi-domain] Cd Length: 141 Bit Score: 72.75 E-value: 4.72e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTD-SLEDDEIEAFYKMLTQREEIDRTFAEAA 243
Cdd:cd16220    1 WVKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENQgTLTFEEFCVFYKMMSLRRDLYLLLLSYS 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 823429468 244 GSREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLS 302
Cdd:cd16220   81 DKKDHLTVEELAQFLKVEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRS 139

EFh_PI-PLCbeta

cd16200

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...

215-304

9.75e-14

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta isozymes; PI-PLC-beta 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 (EC 3.1.4.11). They have been implicated in numerous processes relevant to central nervous system (CNS), including chemotaxis, cardiovascular function, neuronal signaling, and opioid sensitivity. Like other PI-PLC isozymes, PI-PLC-beta 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. Besides, they have 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 PI-PLC-beta isozymes (1-4). PI-PLC-beta1 and PI-PLC-beta3 are expressed in a wide range of tissues and cell types, whereas PI-PLC-beta2 and PI-PLC-beta4 have been found only in hematopoietic and neuronal tissues, respectively. All PI-PLC-beta isozymes are activated by the heterotrimeric G protein alpha subunits of the Gq class through their C2 domain and long C-terminal extension. They are GTPase-activating proteins (GAPs) for these G alpha(q) proteins. PI-PLC-beta2 and PI-PLC-beta3 can also be activated by beta-gamma subunits of the G alpha(i/o) family of heterotrimeric G proteins and the small GTPases such as Rac and Cdc42. This family also includes two invertebrate homologs of PI-PLC-beta, PLC21 from cephalopod retina and No receptor potential A protein (NorpA) from Drosophila melanogaster.

Pssm-ID: 320030 [Multi-domain] Cd Length: 153 Bit Score: 69.20 E-value: 9.75e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 215 DSLEDDEIEAFYKMLTQREEIDRTFAEAAGSREM-LSVDQLVTFLQHQQRE----EAAGPAL----ALSLIERYEPSETA 285
Cdd:cd16200   55 EDFTFEKFFKLYNKLCPRPDIDEIFKELGGKRKPyLTLEQLVDFLNEEQRDprlnEILFPFHtkeqAKKLIDKYEPNEKN 134

                         90
                 ....*....|....*....
gi 823429468 286 KAQRQMTKDGFLMYLLSAD 304
Cdd:cd16200  135 KKKGQLTLEGFLRYLMSDE 153

cd00030

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

685-779

1.07e-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: 67.48 E-value: 1.07e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 685 QVISGQQLPKVNKNKNSivDPKVTVEIHGVGRdvasCQTAVVTNNgFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKN 764
Cdd:cd00030    4 TVIEARNLPAKDLNGKS--DPYVKVSLGGKQK----FKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKD 76

                         90
                 ....*....|....*
gi 823429468 765 DFIGQSTIPLGSLKQ 779
Cdd:cd00030   77 DFLGEVEIPLSELLD 91

PH_PLC_plant-like

cd13365

Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the ...

40-147

1.51e-13

Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the second class of PLC discovered. 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. 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). This cd contains PLC members from fungi and plants. 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: 270171 Cd Length: 115 Bit Score: 67.69 E-value: 1.51e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  40 LQALLKGSQLLKVKSNSWRRERFYKLQEDCKT-IWQESRKVMRTPesqlFSIEDIQEVRKGHRTEGMEKFARDVPEDRCF 118
Cdd:cd13365    7 ITQLKIGSYLLKYGRRGKPHFRYFWLSPDELTlYWSSPKKGSEKR----VRLSSVSRIIPGQRTVVFKRPPPPGLEEHSF 82

                         90       100
                 ....*....|....*....|....*....
gi 823429468 119 SIVFKDQRNTLDLIAPSPAEAQHWVQGLR 147
Cdd:cd13365   83 SIIYADGERSLDLTCKDRQEFDTWFTGLR 111

EFh_PRIP2

cd16223

EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...

165-304

7.19e-10

EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); PRIP-2, also termed phospholipase C-L2, or phospholipase C-epsilon-2 (PLC-epsilon-2), or inactive phospholipase C-like protein 2 (PLC-L2), is a novel inositol 1,4,5-trisphosphate (InsP3) binding protein that exhibits a relatively ubiquitous expression. It functions as a novel negative regulator of B-cell receptor (BCR) signaling and immune responses. PRIP-2 has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, 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-2 does not have PLC enzymatic activity.

Pssm-ID: 320053 [Multi-domain] Cd Length: 144 Bit Score: 57.99 E-value: 7.19e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQ----TDSLEDDEIEAFYKMLTqREEIDRTFA 240
Cdd:cd16223    1 WLSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTSKIELKFKELHKSKekggTEVTKEEFIEVFHELCT-RPEIYFLLV 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 823429468 241 EAAGSREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16223   80 QFSSNKEFLDTKDLMMFLEAEQGMAHVTEEISLDIIHKYEPSKEGQEKGWLSLDGFTNYLMSPE 143

EFh_PI-PLCbeta4

cd16211

EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...

177-304

9.72e-10

EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4, or phospholipase C-beta-4 (PLC-beta4), is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It may play a critical role in linking anxiety behaviors and theta rhythm heterogeneity. PI-PLC-beta4 is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta4 functions as a downstream signaling molecule of type 1 metabotropic glutamate receptors (mGluR1s). The thalamic mGluR1-PI-PLC-beta4 cascade is essential for formalin-induced inflammatory pain by regulating the response of ventral posterolateral thalamic nucleus (VPL) neurons. Moreover, PI-PLC-beta4 is essential for long-term depression (LTD) in the rostral cerebellum, which may be required for the acquisition of the conditioned eyeblink response. Besides, PI-PLC-beta4 may play an important role in maintenance of the status epilepticus. The mutations of PI-PLC-beta4 has been identified as the major cause of autosomal dominant auriculocondylar syndrome (ACS). PI-PLC-beta4 contains 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. Besides, it has 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.

Pssm-ID: 320041 Cd Length: 153 Bit Score: 57.82 E-value: 9.72e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 177 KDNKMSFKELqnflKELNIQvddsyarkifrecdNSQTDSLEDDEI--EAFYKmLTQ----REEIDRTFAEAAG-SREML 249
Cdd:cd16211   30 KTEKIVFQSL----KELGLP--------------SGKNDEIEPEAFtfEKFYE-LYHkicpRTDIEELFKKINGdKKDYL 90

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 823429468 250 SVDQLVTFLQHQQREEAAGPAL--------ALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16211   91 TVDQLISFLNEHQRDPRLNEILfpfydrkrVMQIIETYEVDEEFKKKEQLSSDGFCRYLMSDE 153

PH_PLC_fungal

cd13360

Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been ...

43-162

1.03e-09

Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been characterized in the yeast Saccharomyces cerevisiae via deletion studies which resulted in a pleiotropic phenotype, with defects in growth, carbon source utilization, and sensitivity to osmotic stress and high temperature. Unlike Saccharomyces several other fungi including Neurospora crassa, Cryphonectria parasitica , and Magnaporthe oryzae (Mo) have several PLC proteins, some of which lack a PH domain, with varied functions. MoPLC1-mediated regulation of Ca2+ level is important for conidiogenesis and appressorium formation while both MoPLC2 and MoPLC3 are required for asexual reproduction, cell wall integrity, appressorium development, and pathogenicity. The fungal PLCs in this hierarchy contain an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, and a C-terminal C2 domain. 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: 241514 Cd Length: 118 Bit Score: 56.81 E-value: 1.03e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  43 LLKGSQLLKVKSNSwRRERFYKLQEDCKTIWQESRKvmrtpESQLFSIEDIQEVRKG-----HRTE--GMEKFardvpED 115
Cdd:cd13360    1 LRQGTPLLKVTKKK-KKRILFKLDPESGKITWDSKK-----PSKSLYIDDIKEIRTGedarnYREEfgISEEF-----ED 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 823429468 116 RCFSIVFKDQRN----TLDLIAPSPAEAQHWVQGLRKIIHHsgsmdqRQKL 162
Cdd:cd13360   70 RWITIIYFVPKKnklkTLHLIADTEEDFKLWTTTLEGLVKL------RREL 114

EFh_NorpA_like

cd16212

EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...

215-304

1.12e-09

EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and similar proteins; NorpA, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, is an eye-specific phosphoinositide phospholipase C (PI-PLC) encoded by norpA gene in Drosophila. It is expressed predominantly in photoreceptors and plays an essential role in the phototransduction pathway of Drosophila. A mutation within the norpA gene can render the fly blind without affecting any of the obvious structures of the eye. Like beta-class of vertebrate PI-PLCs, NorpA contains 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.

Pssm-ID: 320042 [Multi-domain] Cd Length: 153 Bit Score: 57.56 E-value: 1.12e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 215 DSLEDDEI--EAFYKM---LTQREEIDRTFAE-AAGSREMLSVDQLVTFLQHQQREEAAGPAL--------ALSLIERYE 280
Cdd:cd16212   50 DSIEKEDFtfEKFYALyhkICPRNDIEELFTSiTKGKGEHISLAQLINFMNDKQRDPRLNEILyplydekrCTEIIKAYE 129

                         90       100
                 ....*....|....*....|....
gi 823429468 281 PSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16212  130 QNEENIKNKRMSKDGFIRYLMSDE 153

EFh_PI-PLCbeta1

cd16208

EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, ...

212-300

2.07e-09

EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1, or PLC-154, or phospholipase C-I (PLC-I), or phospholipase C-beta-1 (PLC-beta1), is expressed at highest levels in specific regions of the brain, as well as in the cardiovascular system. It has two splice variants, PI-PLC-beta1a and PI-PLC-beta1b, both of which are present within the nucleus. Nuclear PI-PLC-beta1 is a key molecule for nuclear inositide signaling, where it plays a role in cell cycle progression, proliferation and differentiation. It also contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta1 acts as an effector and a GTPase activating protein (GAP) specifically activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It regulates neuronal activity in the cerebral cortex and hippocampus, and has been implicated for participations in diverse critical functions related to forebrain diseases such as schizophrenia. It may play an important role in maintenance of the status epilepticus, and in osteosarcoma-related signal transduction pathways. PI-PLC-beta1 also functions as a regulator of erythropoiesis in kinamycin F, a potent inducer of gamma-globin production in K562 cells. The G protein activation and the degradation of PI-PLC-beta1 can be regulated by the interaction of alpha-synuclein. As a result, it may reduce cell damage under oxidative stress. Moreover, PI-PLC-beta1 works as a new intermediate in the HIV-1 gp120-triggered phosphatidylcholine-specific phospholipase C (PC-PLC)-driven signal transduction pathway leading to cytoplasmic CCL2 secretion in macrophages. PI-PLC-beta1 contains 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. Besides, it has 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.

Pssm-ID: 320038 Cd Length: 151 Bit Score: 56.81 E-value: 2.07e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 212 SQTDS--LEDDEIEAFYKMLTQ---REEIDRTFAE-AAGSREMLSVDQLVTFLQHQQRE----EAAGPAL----ALSLIE 277
Cdd:cd16208   45 SRNDSipQEDFTPEVYRVFLNNlcpRPEIDHIFSEfGAKSKPYLSVDQMTEFINSKQRDprlnEILYPPLkqeqVQQLIE 124

                         90       100
                 ....*....|....*....|...
gi 823429468 278 RYEPSETAKAQRQMTKDGFLMYL 300
Cdd:cd16208  125 KYEPNSTLAKKGQISVDGFMRYL 147

EFh_PRIP1

cd16222

EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...

165-304

2.69e-09

EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); PRIP-1, also termed phospholipase C-deleted in lung carcinoma, or inactive phospholipase C-like protein 1 (PLC-L1), or p130, is a novel inositol 1,4,5-trisphosphate (InsP3) binding protein that is predominantly expressed in the brain. It is involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. It interacts with the catalytic subunits of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), and functions as a scaffold to regulate the activities and subcellular localizations of both PP1 and PP2A in phospho-dependent cellular signaling. It also promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of hormone-sensitive lipase (HSL) and perilipin A, thus reducing protein kinase A (PKA)-mediated lipolysis. Moreover, PRIP-1 plays an important role in insulin granule exocytosis through the association with GABAA-receptor-associated protein (GABARAP) to form a complex to regulate KIF5B-mediated insulin secretion. It also inhibits regulated exocytosis through direct interactions with syntaxin 1 and synaptosomal-associated protein 25 (SNAP-25) via its C2 domain. Furthermore, PRIP-1 has been implicated in the negative regulation of bone formation. PRIP-1 has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, 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-1 does not have PLC enzymatic activity.

Pssm-ID: 320052 [Multi-domain] Cd Length: 143 Bit Score: 56.41 E-value: 2.69e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 165 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQ---TDSLEDDEIEAFYKMLTQREEIDRTFAE 241
Cdd:cd16222    1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKeklTTRVTEEEFCEAYSELCTRPEVYFLLVQ 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 823429468 242 AAGSREMLSVDQLVTFLQHQQREEAAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 304
Cdd:cd16222   81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSSE 143

smart00233

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...

43-151

1.59e-08

Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 52.94 E-value: 1.59e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468    43 LLKGSQLLKVKS--NSWRRERFYKLQEDCKTIWQESRKVMRTPESQLFSIEDIQeVRKGHRTEGMEKfardvpeDRCFSI 120
Cdd:smart00233   1 VIKEGWLYKKSGggKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCT-VREAPDPDSSKK-------PHCFEI 72

                           90       100       110
                   ....*....|....*....|....*....|.
gi 823429468   121 VFKDqRNTLDLIAPSPAEAQHWVQGLRKIIH 151
Cdd:smart00233  73 KTSD-RKTLLLQAESEEEREKWVEALRKAIA 102

EFh_PI-PLCbeta3

cd16210

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...

205-300

3.70e-08

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3, or phospholipase C-beta-3 (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. PI-PLC-beta3 associates with CXC chemokine receptor 2 (CXCR2) and Na+/H+ exchanger regulatory factor-1 (NHERF1) to form macromolecular complexes at the plasma membrane of pancreatic cancer cells, which functionally couple chemokine signaling to PI-PLC-beta3-mediated signaling cascade. Moreover, PI-PLC-beta3 directly interacts with the M3 muscarinic receptor (M3R), a prototypical G alpha-q-coupled receptor that promotes PI-PLC-beta3 localization to the plasma membrane. This binding can alter G alpha-q-dependent PLC activation. Furthermore, PI-PLC-beta3 inhibits the proliferation of hematopoietic stem cells (HSCs) and myeloid cells through the interaction of SH2-domain-containing protein phosphatase 1 (SHP-1) and signal transducer and activator of transcription 5 (Stat5), and the augment of the dephosphorylating activity of SHP-1 toward Stat5, leading to the inactivation of Stat5. It is also involved in atopic dermatitis (AD) pathogenesis via regulating the expression of periostin in fibroblasts and thymic stromal lymphopoietin (TSLP) in keratinocytes. In addition, PI-PLC-beta3 mediates the thrombin-induced Ca2+ response in glial cells. PI-PLC-beta3 contains 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. Besides, it has 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.

Pssm-ID: 320040 Cd Length: 151 Bit Score: 53.38 E-value: 3.70e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 205 IFRECDNSQTDSLEDDEIEAFYKMLTQREEIDRTFAE-AAGSREMLSVDQLVTFLQHQQRE----EAAGPAL----ALSL 275
Cdd:cd16210   43 KFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEiGAKGKPYLTLEQLMDFINQKQRDprlnEVLYPPLrpsqVRQL 122

                         90       100
                 ....*....|....*....|....*
gi 823429468 276 IERYEPSETAKAQRQMTKDGFLMYL 300
Cdd:cd16210  123 IEKYEPNQQFLERDQMSMEGFSRYL 147

C2B_Synaptotagmin

cd00276

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...

678-783

1.64e-07

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: 51.04 E-value: 1.64e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 678 HLSFAPT------QVISGQQLPKVNKNKNSivDPKVTVEIHGVGRDVASCQTAVVTNNgFNPWWDTEFVFEV---VVPEL 748
Cdd:cd00276    6 SLSYLPTaerltvVVLKARNLPPSDGKGLS--DPYVKVSLLQGGKKLKKKKTSVKKGT-LNPVFNEAFSFDVpaeQLEEV 82

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 823429468 749 ALVrFLVEDYDASSKNDFIGQSTIPLGSLKQGYRH 783
Cdd:cd00276   83 SLV-ITVVDKDSVGRNEVIGQVVLGPDSGGEELEH 116

COG5038

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

685-780

5.45e-07

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 53.61 E-value: 5.45e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  685 QVISGQQLPKVNKNKNSivDPKVTVEIHGvgrdvASCQTAVVTNNGFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKN 764
Cdd:COG5038  1045 MLRSGENLPSSDENGYS--DPFVKLFLNE-----KSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKN 1117

                          90
                  ....*....|....*.
gi 823429468  765 DFIGQSTIPLGSLKQG 780
Cdd:COG5038  1118 DLLGTAEIDLSKLEPG 1133

PH_12

pfam16457

Pleckstrin homology domain;

40-147

2.33e-06

Pleckstrin homology domain;

Pssm-ID: 465123 [Multi-domain] Cd Length: 128 Bit Score: 47.64 E-value: 2.33e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468   40 LQALLKGSQLLKVKSNS-WRRERFYKLQEDCKTIW----QESRKVMRTPESQLFSIE--DIQEVRKGHRTEGM---EKFA 109
Cdd:pfam16457   6 LNCLLEGAWFPKVRGRRrKKKYRFCRLSPNRKVLHygdfEEKPTVDPSLESLPEKIDlsDIKEVVTGKECPHVresGKKS 85

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 823429468  110 RDVPEDRCFSIVF-KDQRNTLDLIAPSPAEAQHWVQGLR 147
Cdd:pfam16457  86 KKTSSTLAFSLIYgADEYELLDFVAPSESVAAIWLDGLN 124

C2B_Synaptotagmin-7

cd08405

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...

679-785

2.93e-06

C2 domain second 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 47.41 E-value: 2.93e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 679 LSFAPTQ------VISGQQLPKVNKNKNSivDPKVTVEIHGVGRDVASCQTAVVTNNgFNPWWDTEFVFEV---VVPELA 749
Cdd:cd08405    8 LCYNPTAnritvnIIKARNLKAMDINGTS--DPYVKVWLMYKDKRVEKKKTVIKKRT-LNPVFNESFIFNIpleRLRETT 84

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 823429468 750 LVrFLVEDYDASSKNDFIGQstIPLGSLKQGYRHVH 785
Cdd:cd08405   85 LI-ITVMDKDRLSRNDLIGK--IYLGWKSGGLELKH 117

C2B_Munc13-like

cd04009

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...

685-777

3.04e-06

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: 47.23 E-value: 3.04e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 685 QVISGQQLPKVNKNKNSivDPKVTVEI--HGVGRDVASCQTAVVTNNgFNPWWDTEFVFEV----VVPELALVRFLVEDY 758
Cdd:cd04009   21 EILNARNLLPLDSNGSS--DPFVKVELlpRHLFPDVPTPKTQVKKKT-LFPLFDESFEFNVppeqCSVEGALLLFTVKDY 97

                         90
                 ....*....|....*....
gi 823429468 759 DASSKNDFIGQSTIPLGSL 777
Cdd:cd04009   98 DLLGSNDFEGEAFLPLNDI 116

C2_C21orf25-like

cd08678

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...

722-791

8.65e-06

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: 45.82 E-value: 8.65e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 722 QTAVVTNNGfNPWWDTEFVFEvVVPELALVRFLVEDYDASSKNDFIGQSTIPLGSLKQGYRHVHLLSKNG 791
Cdd:cd08678   34 QSSTQKNTS-NPFWDEHFLFE-LSPNSKELLFEVYDNGKKSDSKFLGLAIVPFDELRKNPSGRQIFPLQG 101

C2A_Synaptotagmin-8

cd08387

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...

732-774

2.46e-05

C2A domain first repeat present in Synaptotagmin 8; 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: 176033 [Multi-domain] Cd Length: 124 Bit Score: 44.32 E-value: 2.46e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 823429468 732 NPWWDTEFVFEVVVPELA--LVRFLVEDYDASSKNDFIGQSTIPL 774
Cdd:cd08387   63 NPEFDESFVFEVPPQELPkrTLEVLLYDFDQFSRDECIGVVELPL 107

EFh

cd00051

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...

170-210

2.88e-05

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 42.53 E-value: 2.88e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 823429468 170 LRKA----DKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECD 210
Cdd:cd00051    2 LREAfrlfDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVD 46

EFh_HEF_SCGN

cd16178

EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand ...

146-227

3.06e-05

EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a calcium sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. It also serves as a calcium buffer in neurons. Thus, SCGN may be linked to the pathogenesis of neurological diseases such as Alzheimer's, and also acts as a serum marker of neuronal damage, or as a tumor biomarker. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. All six EF hand motifs of SCGN in some eukaryotes, including D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, could potentially bind six calcium ions. In contrast, SCGNs from higher eukaryotes have at least one non-functional EF-hand motif due to the mutation(s) or deletions. For instance, the EF1 loop does not coordinate calcium ion due to the key residue asparagine replaced by lysine in SCGNs of many mammalian species. Moreover, the EF2 loop seems to be competent for calcium-binding in most mammalian SCGNs except for human and chimpanzee orthologs.

Pssm-ID: 320078 [Multi-domain] Cd Length: 257 Bit Score: 46.24 E-value: 3.06e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 146 LRKIIHHSGSMDQRQKLQHWIHSCLRKADKNKDNKMSFKEL-------QNFLkeLNIQVDDSYAR-------KIFRECDN 211
Cdd:cd16178  118 LRDLFLQHKKVITEDKLDEYTDTMMKIFDKNKDGRLDLNDMarilalqENFL--LQFKMDAMSEEerkrdfeKIFAHYDV 195

                         90
                 ....*....|....*.
gi 823429468 212 SQTDSLEDDEIEAFYK 227
Cdd:cd16178  196 SKTGALEGPEVDGFVK 211

C2A_Copine

cd04048

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...

704-794

3.48e-05

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176013 [Multi-domain] Cd Length: 120 Bit Score: 43.71 E-value: 3.48e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 704 DPKVTVEIHGVGRDVASC--QTAVVTNNgFNPWWDTEFVFEVVVPELALVRFLVEDYDASS----KNDFIGQSTIPLGSL 777
Cdd:cd04048   22 DPFVVVYVKTGGSGQWVEigRTEVIKNN-LNPDFVTTFTVDYYFEEVQKLRFEVYDVDSKSkdlsDHDFLGEAECTLGEI 100

                         90
                 ....*....|....*....
gi 823429468 778 --KQGYRhVHLLSKNGDQH 794
Cdd:cd04048  101 vsSPGQK-LTLPLKGGKGK 118

cd00821

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...

51-146

3.49e-05

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: 43.30 E-value: 3.49e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468  51 KVKSNSWRReRFYKLQEDCKTIWQESRKVMRTPEsQLFSIEDIQEVRKGHRTEgmekfardvpEDRCFSIVFKDQRnTLD 130
Cdd:cd00821   10 GGGLKSWKK-RWFVLFEGVLLYYKSKKDSSYKPK-GSIPLSGILEVEEVSPKE----------RPHCFELVTPDGR-TYY 76

                         90
                 ....*....|....*.
gi 823429468 131 LIAPSPAEAQHWVQGL 146
Cdd:cd00821   77 LQADSEEERQEWLKAL 92

C2D_Tricalbin-like

cd04040

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...

685-777

6.11e-05

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: 42.94 E-value: 6.11e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 685 QVISGQQLPKVNKNKNSivDPKVTVEIHGvgRDVAscQTAVVTNNgFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKN 764
Cdd:cd04040    4 DVISAENLPSADRNGKS--DPFVKFYLNG--EKVF--KTKTIKKT-LNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKD 76

                         90
                 ....*....|...
gi 823429468 765 DFIGQSTIPLGSL 777
Cdd:cd04040   77 DLLGSAYIDLSDL 89

C2_NEDD4_NEDD4L

cd04033

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...

685-777

9.04e-05

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. 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: 175999 [Multi-domain] Cd Length: 133 Bit Score: 43.11 E-value: 9.04e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 685 QVISGQQLPKvnKNKNSIVDP--KVTVEIHGVGRDVASCQTAVVTNNgFNPWWDTEFVFEVVVPELALVrFLVEDYDASS 762
Cdd:cd04033    5 KVLAGIDLAK--KDIFGASDPyvKISLYDPDGNGEIDSVQTKTIKKT-LNPKWNEEFFFRVNPREHRLL-FEVFDENRLT 80

                         90
                 ....*....|....*
gi 823429468 763 KNDFIGQSTIPLGSL 777
Cdd:cd04033   81 RDDFLGQVEVPLNNL 95

EFh_PI-PLCgamma

cd16201

EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...

170-267

1.14e-04

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: 42.94 E-value: 1.14e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 170 LRK----ADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKMLTQRE-EIDRTFAEAAG 244
Cdd:cd16201    2 LRKefysMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDTRRRGELGFDDFAQLYHKLMFDQkIIEDFFKKYSY 81

                         90       100
                 ....*....|....*....|....*....
gi 823429468 245 SREmlsvDQLVT------FLQHQQREEAA 267
Cdd:cd16201   82 SSD----GQTVTledfqrFLLEEQKEPWA 106

pfam00169

PH domain; PH stands for pleckstrin homology.

51-151

1.43e-04

PH domain; PH stands for pleckstrin homology.

Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 41.78 E-value: 1.43e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468   51 KVKSNSWRReRFYKLQEDCKTIWQESRKVMRTPESQLFSIEDIQEVRKGHRTEGmekfardvPEDRCFSIVFKDQRN--T 128
Cdd:pfam00169  12 GGKKKSWKK-RYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEVVEVVASDSP--------KRKFCFELRTGERTGkrT 82

                          90       100
                  ....*....|....*....|...
gi 823429468  129 LDLIAPSPAEAQHWVQGLRKIIH 151
Cdd:pfam00169  83 YLLQAESEEERKDWIKAIQSAIR 105

FRQ1

COG5126

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

157-266

2.07e-04

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 42.09 E-value: 2.07e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 157 DQRQKLQHWIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYKML-TQREEI 235
Cdd:COG5126   26 DFEALFRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALgVSEEEA 105

                         90       100       110
                 ....*....|....*....|....*....|..
gi 823429468 236 DRTFAEAAGSR-EMLSVDQLVTFLQHQQREEA 266
Cdd:COG5126  106 DELFARLDTDGdGKISFEEFVAAVRDYYTPDA 137

C2B_Munc13

cd04027

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...

684-777

2.33e-04

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: 41.79 E-value: 2.33e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 684 TQVISGQQLpkVNKNKNSIVDPKVTVEIHGVGRdvascQTAVVTNNgFNPWWDTEFVFEV-VVPELALVRFLVEDYDASS 762
Cdd:cd04027    5 ITVVCAQGL--IAKDKTGTSDPYVTVQVGKTKK-----RTKTIPQN-LNPVWNEKFHFEChNSSDRIKVRVWDEDDDIKS 76

                         90       100
                 ....*....|....*....|....
gi 823429468 763 K---------NDFIGQSTIPLGSL 777
Cdd:cd04027   77 RlkqkftresDDFLGQTIIEVRTL 100

C2_putative_Elicitor-responsive_gene

cd04049

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...

697-777

2.67e-04

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: 41.55 E-value: 2.67e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 697 KNKNSIVDPKVTVEIHGVGRDVAScqtAVVTNNGFNPWWDTEFVFEVVVPELALVRFL---VEDYDASSKNDFIGQSTIP 773
Cdd:cd04049   14 QDTDFLGKIDPYVIIQCRTQERKS---KVAKGDGRNPEWNEKFKFTVEYPGWGGDTKLilrIMDKDNFSDDDFIGEATIH 90


                 ....
gi 823429468 774 LGSL 777
Cdd:cd04049   91 LKGL 94

C2B_RasA1_RasA4

cd04025

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...

685-779

3.39e-04

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: 41.32 E-value: 3.39e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 685 QVISGQQLPKvnKNKNSIVDPKVTVEIHGvgrdvASCQTAVVTNNGFnPWWDTEFVFEVVVPELALVRFLVEDYDASSKN 764
Cdd:cd04025    5 HVLEARDLAP--KDRNGTSDPFVRVFYNG-----QTLETSVVKKSCY-PRWNEVFEFELMEGADSPLSVEVWDWDLVSKN 76

                         90
                 ....*....|....*
gi 823429468 765 DFIGQSTIPLGSLKQ 779
Cdd:cd04025   77 DFLGKVVFSIQTLQQ 91

C2A_RIM1alpha

cd04031

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...

722-776

3.50e-04

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). 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-I topology and do not bind Ca2+.

Pssm-ID: 175997 [Multi-domain] Cd Length: 125 Bit Score: 41.08 E-value: 3.50e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 823429468 722 QTAVVTNNgFNPWWDTEFVFEVVVPELALVRFL---VEDYDASSKNDFIGQSTIPLGS 776
Cdd:cd04031   56 RTKTVKKT-LNPEWNQTFEYSNVRRETLKERTLevtVWDYDRDGENDFLGEVVIDLAD 112

C2E_Ferlin

cd04037

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

729-774

5.94e-04

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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: 176002 [Multi-domain] Cd Length: 124 Bit Score: 40.61 E-value: 5.94e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 823429468 729 NGFNPWWDTEFVFEVVVPELALVRFLVEDYDASSKNDFIGQSTIPL 774
Cdd:cd04037   43 NTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDLIGETVIDL 88

C2A_C2C_Synaptotagmin_like

cd08391

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...

686-781

6.22e-04

C2 domain first and third repeat 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 either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 40.35 E-value: 6.22e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 686 VISGQQLPKVNKNKNSIV----DPKVTVEihgVGRDvaSCQTAVVTNNgFNPWWDTefVFEVVVPELALVRFLVEDYDAS 761
Cdd:cd08391    7 VIEAQDLVAKDKFVGGLVkgksDPYVIVR---VGAQ--TFKSKVIKEN-LNPKWNE--VYEAVVDEVPGQELEIELFDED 78

                         90       100
                 ....*....|....*....|..
gi 823429468 762 -SKNDFIGQSTIPLGS-LKQGY 781
Cdd:cd08391   79 pDKDDFLGRLSIDLGSvEKKGF 100

EFh_HEF

cd15902

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...

160-236

6.46e-04

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.

Pssm-ID: 320075 [Multi-domain] Cd Length: 254 Bit Score: 42.34 E-value: 6.46e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 160 QKLQHWIHSCLRKADKNKDNKMSFKEL-------QNFLKELNIQVDDSYAR----KIFRECDNSQTDSLEDDEIEAFYK- 227
Cdd:cd15902  130 PKLDEYTKLILKEFDANKDGKLELDEMakllpvqENFLLKFQILGAMDLTKedfeKVFEHYDKDNNGVIEGNELDALLKd 209

                         90
                 ....*....|
gi 823429468 228 -MLTQREEID 236
Cdd:cd15902  210 lLEKNKADID 219

C2B_Rabphilin_Doc2

cd08384

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...

719-768

7.35e-04

C2 domain second 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 40.41 E-value: 7.35e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 823429468 719 ASCQTAVVTNNGFNPWWDTEFVFEVVVPELAlVRFL---VEDYDASSKNDFIG 768
Cdd:cd08384   49 KSKHKTQVKKKTLNPEFNEEFFYDIKHSDLA-KKTLeitVWDKDIGKSNDYIG 100

C2_Ras_p21A1

cd08400

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...

717-780

8.34e-04

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, 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. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. 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-I topology.

Pssm-ID: 176045 [Multi-domain] Cd Length: 126 Bit Score: 40.04 E-value: 8.34e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 823429468 717 DVASCQTAVVTnnGFNPWWDTEFVFEVVVPElaLVRFLVEDYDAS--SKNDFIGQSTIPLGSLKQG 780
Cdd:cd08400   32 EVKVARTKVRE--GPNPVWSEEFVFDDLPPD--VNSFTISLSNKAkrSKDSEIAEVTVQLSKLQNG 93

PH_PLC_gamma

cd13362

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...

90-150

9.33e-04

Phospholipase C-gamma (PLC-gamma) 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. Only the first 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: 270168 Cd Length: 121 Bit Score: 39.95 E-value: 9.33e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 823429468  90 IEDIQEVRKGHRTEGMEKF---ARDVPEDRCFSIVFKDQ--RNTLDLIAPSPAEAQHWVQGLRKII 150
Cdd:cd13362   46 IREIKEIRPGKNSKDFERWpdeAKKLDPSCCFVILYGTEfrLKTLSVAATSEEECDMWIKGLRYLV 111

C2B_Synaptotagmin-1

cd08402

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...

704-783

1.05e-03

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. 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: 176047 [Multi-domain] Cd Length: 136 Bit Score: 40.08 E-value: 1.05e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 704 DPKVTVEIHGVGRDVASCQTAVvTNNGFNPWWDTEFVFEVVVPELALVRFLVE--DYDASSKNDFIGQSTIPLGSLKQGY 781
Cdd:cd08402   37 DPYVKIHLMQNGKRLKKKKTTI-KKRTLNPYYNESFSFEVPFEQIQKVHLIVTvlDYDRIGKNDPIGKVVLGCNATGAEL 115


                 ..
gi 823429468 782 RH 783
Cdd:cd08402  116 RH 117

EFh_PI-PLCbeta2

cd16209

EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, ...

219-300

1.10e-03

EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2, or phospholipase C-beta-2 (PLC-beta2), is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits (G alpha(q)) through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins. PI-PLC-beta2 has two cellular binding partners, alpha- and gamma-synuclein. The binding of either alpha- and gamma-synuclein inhibits PI-PLC-beta2 activity through preventing the binding of its activator G alpha(q). However, the binding of gamma-synuclein to PI-PLC-beta2 does not affect its binding to G beta(gamma) subunits or small G proteins, but enhances these signals. Meanwhile, gamma-synuclein may protect PI-PLC-beta2 from protease degradation and contribute to its over-expression in breast cancer. In leukocytes, the G beta(gamma)-mediated activation of PI-PLC-beta2 can be promoted by a scaffolding protein WDR26, which is also required for the translocation of PI-PLC-beta2 from the cytosol to the membrane in polarized leukocytes. PI-PLC-beta2 contains 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. Besides, it has 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.

Pssm-ID: 320039 Cd Length: 151 Bit Score: 40.25 E-value: 1.10e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 219 DDEIEAFYKM----LTQREEIDRTFAE-AAGSREMLSVDQLVTFLQHQQREE--------AAGPALALSLIERYEPSETA 285
Cdd:cd16209   53 EDFPEAVFKTflmqLCPRPEIDEIFTSyHAKAKPYMTKEHLTKFINKKQRDSrlneelfpPARPDQVQGLIEKYEPSGIN 132

                         90
                 ....*....|....*
gi 823429468 286 KAQRQMTKDGFLMYL 300
Cdd:cd16209  133 AQRGQLSPEGMVWFL 147

C2_KIAA0528-like

cd08688

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...

685-777

1.26e-03

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. 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: 176070 [Multi-domain] Cd Length: 110 Bit Score: 39.21 E-value: 1.26e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 685 QVISGQQLPKVNKNKNSiVDPKVTVEIhgvGRDVAscQTAVVTNNgFNPWWDTE-FVFEVvvPELAL----VRFLVEDYD 759
Cdd:cd08688    4 RVVAARDLPVMDRSSDL-TDAFVEVKF---GSTTY--KTDVVKKS-LNPVWNSEwFRFEV--DDEELqdepLQIRVMDHD 74

                         90
                 ....*....|....*...
gi 823429468 760 ASSKNDFIGQSTIPLGSL 777
Cdd:cd08688   75 TYSANDAIGKVYIDLNPL 92

PI-PLCc_bacteria_like

cd08557

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...

322-438

1.45e-03

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: 41.31 E-value: 1.45e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 322 PLSHYLMSSSHNTY-----LLEDQLTGPSST-EAYIR-ALCKGCRCVELDCWDGPNQEPI-IYHGYTFTSKILLCDVLRA 393
Cdd:cd08557    8 PLSQLSIPGTHNSYaytidGNSPIVSKWSKTqDLSITdQLDAGVRYLDLRVAYDPDDGDLyVCHGLFLLNGQTLEDVLNE 87

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 823429468 394 IRDYAfKASPY-PVILSLENHCSLEQQRVMA---RHLRTILGPMLLDRP 438
Cdd:cd08557   88 VKDFL-DAHPSeVVILDLEHEYGGDNGEDHDeldALLRDVLGDPLYRPP 135

C2B_RasGAP

cd08675

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...

684-779

4.77e-03

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 38.12 E-value: 4.77e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 684 TQVISGQQLPKVNkNKNSivDPKVTVEIHGVGRDVAScQTAVV--TNNgfnPWWDTEFVFEVVVPE-------------L 748
Cdd:cd08675    3 VRVLECRDLALKS-NGTC--DPFARVTLNYSSKTDTK-RTKVKkkTNN---PRFDEAFYFELTIGFsyekksfkveeedL 75

                         90       100       110
                 ....*....|....*....|....*....|...
gi 823429468 749 ALVRFLVEDYDAS--SKNDFIGQSTIPLGSLKQ 779
Cdd:cd08675   76 EKSELRVELWHASmvSGDDFLGEVRIPLQGLQQ 108

C2A_Synaptotagmin-1-5-6-9-10

cd08385

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...

732-776

5.07e-03

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. 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: 176031 [Multi-domain] Cd Length: 124 Bit Score: 37.63 E-value: 5.07e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 823429468 732 NPWWDTEFVFEVVVPELA--LVRFLVEDYDASSKNDFIGQSTIPLGS 776
Cdd:cd08385   63 NPVFNETFTFKVPYSELGnkTLVFSVYDFDRFSKHDLIGEVRVPLLT 109

C2A_MCTP_PRT

cd04042

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...

732-805

5.19e-03

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three 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: 176007 [Multi-domain] Cd Length: 121 Bit Score: 37.64 E-value: 5.19e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 823429468 732 NPWWDTEFVFEVVVPElALVRFLVEDYDASSKNDFIGQSTIPLGSLKQGYR---HVHLLSKNGDqHPSATLFVKVSL 805
Cdd:cd04042   45 NPVWDEKFTLPIEDVT-QPLYIKVFDYDRGLTDDFMGSAFVDLSTLELNKPtevKLKLEDPNSD-EDLGYISLVVTL 119

C2B_Synaptotagmin-4

cd08404

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...

686-791

6.42e-03

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. 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: 176049 [Multi-domain] Cd Length: 136 Bit Score: 37.79 E-value: 6.42e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 686 VISGQQLPKVNKNKNSivDPKVTVEIHGVGRDVASCQTAVvTNNGFNPWWDTEFVFEVVVPEL--ALVRFLVEDYDASSK 763
Cdd:cd08404   21 VLKARHLPKMDVSGLA--DPYVKVNLYYGKKRISKKKTHV-KKCTLNPVFNESFVFDIPSEELedISVEFLVLDSDRVTK 97

                         90       100
                 ....*....|....*....|....*...
gi 823429468 764 NDFIGQSTIPLGSLKQGYRHVHLLSKNG 791
Cdd:cd08404   98 NEVIGRLVLGPKASGSGGHHWKEVCNPP 125

C2C_MCTP_PRT

cd08377

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...

686-787

6.76e-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: 37.28 E-value: 6.76e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 823429468 686 VISGQQLPKVNKNKNSivDPKVTVEihgVGRDVASCQTAVVTnngFNPWWDTEFVFEV----VVPELAlvrflVEDYDAS 761
Cdd:cd08377    7 VIRASGLAAADIGGKS--DPFCVLE---LVNARLQTHTIYKT---LNPEWNKIFTFPIkdihDVLEVT-----VYDEDKD 73

                         90       100
                 ....*....|....*....|....*.
gi 823429468 762 SKNDFIGQSTIPLGSLKQGYRHVHLL 787
Cdd:cd08377   74 KKPEFLGKVAIPLLSIKNGERKWYAL 99

EF-hand_7

pfam13499

EF-hand domain pair;

165-227

6.81e-03

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 35.69 E-value: 6.81e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 823429468  165 WIHSCLRKADKNKDNKMSFKELQNFLK--ELNIQVDDSYARKIFRECDNSQTDSLEDDEIEAFYK 227
Cdd:pfam13499   3 KLKEAFKLLDSDGDGYLDVEELKKLLRklEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

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