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Conserved domains on  [gi|2462542789|ref|XP_054233279|]
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cytosolic phospholipase A2 epsilon isoform X1 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Patatin_and_cPLA2 super family cl11396
Patatins and Phospholipases; Patatin-like phospholipase. This family consists of various ...
 291-551 1.03e-167

Patatins and Phospholipases; Patatin-like phospholipase. This family consists of various patatin glycoproteins from plants. The patatin protein accounts for up to 40% of the total soluble protein in potato tubers. Patatin is a storage protein, but it also has the enzymatic activity of a lipid acyl hydrolase, catalyzing the cleavage of fatty acids from membrane lipids. Members of this family have also been found in vertebrates. This family also includes the catalytic domain of cytosolic phospholipase A2 (PLA2; EC 3.1.1.4) hydrolyzes the sn-2-acyl ester bond of phospholipids to release arachidonic acid. At the active site, cPLA2 contains a serine nucleophile through which the catalytic mechanism is initiated. The active site is partially covered by a solvent-accessible flexible lid. cPLA2 displays interfacial activation as it exists in both "closed lid" and "open lid" forms.


The actual alignment was detected with superfamily member cd07201:

Pssm-ID: 416256 [Multi-domain]  Cd Length: 541  Bit Score: 488.77  E-value: 1.03e-167
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 291 MKSTPCPETLDVRLGFSLCPAELEFLQKRKVVVAKALKQVLQLEEDLQEDEVPLIAIMATGGGTRSMTSMYGHLLGLQKL 370
Cdd:cd07201     1 LKAEESSEDLDVRLGFDLCAEEQEFLQKRKKVVAAALKKALQLEEDLQEDEVPVVAVMTTGGGTRALTSMYGSLLGLQKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 371 NLLDCASYITGLSGATWTMATLYRDPDWSSKNLEPAIFEARRHVVKDKLPSLFPDQLRKFQEELRQRSQEGYRVTFTDFW 450
Cdd:cd07201    81 GLLDCVSYITGLSGSTWTMATLYEDPNWSQKDLEGPIEEARKHVTKSKLGCFSPERLKYYRQELSEREQEGHKVSFIDLW 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 451 GLLIETCLGDERNECKLSDQRAALSCGQNPLPIYLTINVKDDVSNQDFREWFEFSPYEVGLQKYGAFIPSELFGSEFFMG 530
Cdd:cd07201   161 GLIIESMLHDKKNDHKLSDQREAVSQGQNPLPIYLSLNVKDNLSTQDFREWVEFTPYEVGFLKYGAFIPAEDFGSEFFMG 240

                         250       260
                  ....*....|....*....|.
gi 2462542789 531 RLVKRIPESRICYMLASASSV 551
Cdd:cd07201   241 RLMKKLPESRICFLQGMWSSI 261
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 40-148 1.40e-58

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


:

Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 191.71  E-value: 1.40e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  40 LLTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVtPDD 119
Cdd:cd04036     1 LLTVRVLRATNITKGDLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV-MDD 79

                          90       100
                  ....*....|....*....|....*....
gi 2462542789 120 HLLTVLYDLTKLCFRKKTHVKFPLNPQGM 148
Cdd:cd04036    80 HLGTVLFDVSKLKLGEKVRVTFSLNPQGK 108
cPLA2_C2 pfam18695
Cytosolic phospholipases A2 C2-domain; Cytosolic phospholipases A2 (cPLA2s) consist of a ...
 180-292 2.63e-35

Cytosolic phospholipases A2 C2-domain; Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. In humans, the cPLA2 family contains six isoforms. Structural information of full length cPLA2alpha apo form, shows that it is composed of two domains; an N-terminal Ca2 + binding C2 domain and a C-terminal alpha/beta hydrolase core. This entry describes the N-terminal Ca2+ binding C2 domain which is composed of an eight-stranded antiparallel beta-sandwich consisting of two four-stranded beta-sheets. C2 domains are present in many lipid-binding proteins including Copines, CAPRI and Rabphilin-3A all of which are involved in membrane trafficking.


:

Pssm-ID: 465834  Cd Length: 111  Bit Score: 128.53  E-value: 2.63e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 180 CLEVHAQSRRRRKREKMKDLLVMVNESFENTQRVRPCLEPCCPTSacfqtaACFHYPKYFQSQVHVEVPKSHWSCGLCCR 259
Cdd:pfam18695   1 CLEVQVDSRGSKKEQGKKDLQLTVPGSYEGTQTISLGPEPGCPDP------FCFHYPKYWEPELHVELPKSSVLQSGWNS 74

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462542789 260 SRKKGPI--SQPLDCLSDGQVMTLPVGESYELHMK 292
Cdd:pfam18695  75 DLEKETSklTVPLKSLPLGQEVTVPLPEGQELHLR 109
 
Name Accession Description Interval E-value
cPLA2_Grp-IVB-IVD-IVE-IVF cd07201
Group IVB, IVD, IVE, and IVF cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group ...
 291-551 1.03e-167

Group IVB, IVD, IVE, and IVF cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group IVB, IVD, IVE, and IVF cPLA2 consists of two domains: the regulatory C2 domain and alpha/beta hydrolase PLA2 domain. Group IVB, IVD, IVE, and IVF cPLA2 are also referred to as cPLA2-beta, -delta, -epsilon, and -zeta respectively. cPLA2-beta is approximately 30% identical to cPLA2-alpha and it shows low enzymatic activity compared to cPLA2alpha. cPLA2-beta hydrolyzes palmitic acid from 1-[14C]palmitoyl-2-arachidonoyl-PC and arachidonic acid from 1-palmitoyl-2[14C]arachidonoyl-PC, but not from 1-O-alkyl-2[3H]arachidonoyl-PC. cPLA2-delta, -epsilon, and -zeta are approximately 45-50% identical to cPLA2-beta and 31-37% identical to cPLA2-alpha. It's possible that cPLA2-beta, -delta, -epsilon, and -zeta may have arisen by gene duplication from an ancestral gene. The catalytic domain of cytosolic phospholipase A2 (PLA2; EC 3.1.1.4) hydrolyzes the sn-2-acyl ester bond of phospholipids to release arachidonic acid. At the active site, cPLA2 contains a serine nucleophile through which the catalytic mechanism is initiated. The active site is partially covered by a solvent-accessible flexible lid. cPLA2 displays interfacial activation as it exists in both "closed lid" and "open lid" forms. Movement of the cPLA2 lid possibly exposes a greater hydrophobic surface and the active site. cPLA2 belongs to the alpha-beta hydrolase family which is identified by a characteristic nucleophile elbow with a consensus sequence of Sm-X-Nu-Sm (Sm = small residue, X = any residue and Nu = nucleophile). Calcium is required for cPLA2 to bind with membranes or phospholipids. The calcium-dependent phospholipid binding domain resides in the N-terminal region of cPLA2; it is homologous to the C2 domain superfamily which is not included in this hierarchy. It includes PLA2G4B, PLA2G4D, PLA2G4E, and PLA2G4F from humans.


Pssm-ID: 132840 [Multi-domain]  Cd Length: 541  Bit Score: 488.77  E-value: 1.03e-167
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 291 MKSTPCPETLDVRLGFSLCPAELEFLQKRKVVVAKALKQVLQLEEDLQEDEVPLIAIMATGGGTRSMTSMYGHLLGLQKL 370
Cdd:cd07201     1 LKAEESSEDLDVRLGFDLCAEEQEFLQKRKKVVAAALKKALQLEEDLQEDEVPVVAVMTTGGGTRALTSMYGSLLGLQKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 371 NLLDCASYITGLSGATWTMATLYRDPDWSSKNLEPAIFEARRHVVKDKLPSLFPDQLRKFQEELRQRSQEGYRVTFTDFW 450
Cdd:cd07201    81 GLLDCVSYITGLSGSTWTMATLYEDPNWSQKDLEGPIEEARKHVTKSKLGCFSPERLKYYRQELSEREQEGHKVSFIDLW 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 451 GLLIETCLGDERNECKLSDQRAALSCGQNPLPIYLTINVKDDVSNQDFREWFEFSPYEVGLQKYGAFIPSELFGSEFFMG 530
Cdd:cd07201   161 GLIIESMLHDKKNDHKLSDQREAVSQGQNPLPIYLSLNVKDNLSTQDFREWVEFTPYEVGFLKYGAFIPAEDFGSEFFMG 240

                         250       260
                  ....*....|....*....|.
gi 2462542789 531 RLVKRIPESRICYMLASASSV 551
Cdd:cd07201   241 RLMKKLPESRICFLQGMWSSI 261
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 40-148 1.40e-58

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


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 191.71  E-value: 1.40e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  40 LLTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVtPDD 119
Cdd:cd04036     1 LLTVRVLRATNITKGDLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV-MDD 79

                          90       100
                  ....*....|....*....|....*....
gi 2462542789 120 HLLTVLYDLTKLCFRKKTHVKFPLNPQGM 148
Cdd:cd04036    80 HLGTVLFDVSKLKLGEKVRVTFSLNPQGK 108
PLAc smart00022
Cytoplasmic phospholipase A2, catalytic subunit; Cytosolic phospholipases A2 hydrolyse ...
 284-535 3.41e-38

Cytoplasmic phospholipase A2, catalytic subunit; Cytosolic phospholipases A2 hydrolyse arachidonyl phospholipids. Family includes phospholipases B isoforms.


Pssm-ID: 214474  Cd Length: 549  Bit Score: 148.73  E-value: 3.41e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  284 GESYELHMKSTPCPETLdVRLGFSLCPAELEFLQKRKVVVAKALKQVLQLE-------EDLQEDEVPLIAIMATGGGTRS 356
Cdd:smart00022  11 VDSYAPYNVSCPSDIPL-VRFSMGLSDNETEFLQKRKDYTNEAMKSFLGRAnsnfldsSLLNSSDVPKIAIAGSGGGFRA 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  357 MTS-------MYGHLLGLQKLNLLDCASYITGLSGATWTMATLYRDPDWSSKNLEPAIFE-ARRHVVKDKLPSLF--PDQ 426
Cdd:smart00022  90 MVGgagvlkaMDNRTDGHGLGGLLQSATYLAGLSGGTWLVGTLASNNFTPVKGPEEINSEwMFSVSINNPGINLLltAQF 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  427 LRKFQEELRQRSQEGYRVTFTDFWGLLIETCLGD--ERNECKLSDQRAA--LSCGQNPLPIYLTINVKDDVSNQDFREW- 501
Cdd:smart00022 170 YKSIVDAVWKKKDAGFNISLTDIWGRALSYNLFDslGGPNYTLSSLRDQekFQNAEMPLPIFVADGRKPGESVINFNDTv 249

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 2462542789  502 FEFSPYEVGL--QKYGAFIPSELFGSEFFMGRLVKR 535
Cdd:smart00022 250 FEFSPFEFGSwdPKLNAFMPPEYLGSKFFNGTPVKK 285
cPLA2_C2 pfam18695
Cytosolic phospholipases A2 C2-domain; Cytosolic phospholipases A2 (cPLA2s) consist of a ...
 180-292 2.63e-35

Cytosolic phospholipases A2 C2-domain; Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. In humans, the cPLA2 family contains six isoforms. Structural information of full length cPLA2alpha apo form, shows that it is composed of two domains; an N-terminal Ca2 + binding C2 domain and a C-terminal alpha/beta hydrolase core. This entry describes the N-terminal Ca2+ binding C2 domain which is composed of an eight-stranded antiparallel beta-sandwich consisting of two four-stranded beta-sheets. C2 domains are present in many lipid-binding proteins including Copines, CAPRI and Rabphilin-3A all of which are involved in membrane trafficking.


Pssm-ID: 465834  Cd Length: 111  Bit Score: 128.53  E-value: 2.63e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 180 CLEVHAQSRRRRKREKMKDLLVMVNESFENTQRVRPCLEPCCPTSacfqtaACFHYPKYFQSQVHVEVPKSHWSCGLCCR 259
Cdd:pfam18695   1 CLEVQVDSRGSKKEQGKKDLQLTVPGSYEGTQTISLGPEPGCPDP------FCFHYPKYWEPELHVELPKSSVLQSGWNS 74

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462542789 260 SRKKGPI--SQPLDCLSDGQVMTLPVGESYELHMK 292
Cdd:pfam18695  75 DLEKETSklTVPLKSLPLGQEVTVPLPEGQELHLR 109
PLA2_B pfam01735
Lysophospholipase catalytic domain; This family consists of Lysophospholipase / phospholipase ...
 345-535 1.39e-27

Lysophospholipase catalytic domain; This family consists of Lysophospholipase / phospholipase B EC:3.1.1.5 and cytosolic phospholipase A2 EC:3.1.4 which also has a C2 domain pfam00168. Phospholipase B enzymes catalyze the release of fatty acids from lysophsopholipids and are capable in vitro of hydrolysing all phospholipids extractable form yeast cells. Cytosolic phospholipase A2 associates with natural membranes in response to physiological increases in Ca2+ and selectively hydrolyses arachidonyl phospholipids, the aligned region corresponds the the carboxy-terminal Ca2+-independent catalytic domain of the protein as discussed in.


Pssm-ID: 366778  Cd Length: 490  Bit Score: 116.70  E-value: 1.39e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 345 IAIMATGGGTRSMTSMYG--------HLLGLQKLNLLDCASYITGLSGATWTMATLYRD-----PDWSSKNLEPAIfEAR 411
Cdd:pfam01735   1 IGIAGSGGGYRAMLGGAGvlaaldnrTDNETGLGGLLQSATYLAGLSGGSWLVGSLAVNnftsvQDFPDKPEDISI-WDL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 412 RHVVKDKLPSLFPDQLRKFQ---EELRQRSQEGYRVTFTDFWGLLIETCLGD---ERNECKLSDQRAA--LSCGQNPLPI 483
Cdd:pfam01735  80 NHSIFNPGGLNIPQNIKRYDdivDAVWKKKNAGFNVSLTDIWGRALSYTLIPslrGGPNYTWSSLRDAewFQNAEMPFPI 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2462542789 484 YLTINVKDDVSNQDFR-EWFEFSPYEVGL--QKYGAFIPSELFGSEFFMGRLVKR 535
Cdd:pfam01735 160 IVADGRKPGTTVINLNaTVFEFSPYEFGSwdPTLNSFTPTEYLGTKFFNGTPVKK 214
C2 pfam00168
C2 domain;
39-143 2.61e-21

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 88.92  E-value: 2.61e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  39 HLLTVRVIRMKNVRQADMLSQTDCFVSLWLpTASQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPD 118
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYL-LDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*
gi 2462542789 119 DHLLTVLYDLTKLCFRKKTHVKFPL 143
Cdd:pfam00168  80 DFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 40-132 1.75e-19

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: 83.69  E-value: 1.75e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789   40 LLTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPDD 119
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                           90
                   ....*....|...
gi 2462542789  120 HLLTVLYDLTKLC 132
Cdd:smart00239  81 FIGQVTIPLSDLL 93
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
41-147 2.33e-10

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 64.01  E-value: 2.33e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789   41 LTVRVIRMKNVRQADMLSQTDCFVSLWLptASQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPDDH 120
Cdd:COG5038   1042 LTIMLRSGENLPSSDENGYSDPFVKLFL--NEKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDL 1119

                           90       100
                   ....*....|....*....|....*..
gi 2462542789  121 LLTVLYDLTKLCFRKKTHVKFPLNPQG 147
Cdd:COG5038   1120 LGTAEIDLSKLEPGGTTNSNIPLDGKT 1146
 
Name Accession Description Interval E-value
cPLA2_Grp-IVB-IVD-IVE-IVF cd07201
Group IVB, IVD, IVE, and IVF cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group ...
 291-551 1.03e-167

Group IVB, IVD, IVE, and IVF cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group IVB, IVD, IVE, and IVF cPLA2 consists of two domains: the regulatory C2 domain and alpha/beta hydrolase PLA2 domain. Group IVB, IVD, IVE, and IVF cPLA2 are also referred to as cPLA2-beta, -delta, -epsilon, and -zeta respectively. cPLA2-beta is approximately 30% identical to cPLA2-alpha and it shows low enzymatic activity compared to cPLA2alpha. cPLA2-beta hydrolyzes palmitic acid from 1-[14C]palmitoyl-2-arachidonoyl-PC and arachidonic acid from 1-palmitoyl-2[14C]arachidonoyl-PC, but not from 1-O-alkyl-2[3H]arachidonoyl-PC. cPLA2-delta, -epsilon, and -zeta are approximately 45-50% identical to cPLA2-beta and 31-37% identical to cPLA2-alpha. It's possible that cPLA2-beta, -delta, -epsilon, and -zeta may have arisen by gene duplication from an ancestral gene. The catalytic domain of cytosolic phospholipase A2 (PLA2; EC 3.1.1.4) hydrolyzes the sn-2-acyl ester bond of phospholipids to release arachidonic acid. At the active site, cPLA2 contains a serine nucleophile through which the catalytic mechanism is initiated. The active site is partially covered by a solvent-accessible flexible lid. cPLA2 displays interfacial activation as it exists in both "closed lid" and "open lid" forms. Movement of the cPLA2 lid possibly exposes a greater hydrophobic surface and the active site. cPLA2 belongs to the alpha-beta hydrolase family which is identified by a characteristic nucleophile elbow with a consensus sequence of Sm-X-Nu-Sm (Sm = small residue, X = any residue and Nu = nucleophile). Calcium is required for cPLA2 to bind with membranes or phospholipids. The calcium-dependent phospholipid binding domain resides in the N-terminal region of cPLA2; it is homologous to the C2 domain superfamily which is not included in this hierarchy. It includes PLA2G4B, PLA2G4D, PLA2G4E, and PLA2G4F from humans.


Pssm-ID: 132840 [Multi-domain]  Cd Length: 541  Bit Score: 488.77  E-value: 1.03e-167
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 291 MKSTPCPETLDVRLGFSLCPAELEFLQKRKVVVAKALKQVLQLEEDLQEDEVPLIAIMATGGGTRSMTSMYGHLLGLQKL 370
Cdd:cd07201     1 LKAEESSEDLDVRLGFDLCAEEQEFLQKRKKVVAAALKKALQLEEDLQEDEVPVVAVMTTGGGTRALTSMYGSLLGLQKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 371 NLLDCASYITGLSGATWTMATLYRDPDWSSKNLEPAIFEARRHVVKDKLPSLFPDQLRKFQEELRQRSQEGYRVTFTDFW 450
Cdd:cd07201    81 GLLDCVSYITGLSGSTWTMATLYEDPNWSQKDLEGPIEEARKHVTKSKLGCFSPERLKYYRQELSEREQEGHKVSFIDLW 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 451 GLLIETCLGDERNECKLSDQRAALSCGQNPLPIYLTINVKDDVSNQDFREWFEFSPYEVGLQKYGAFIPSELFGSEFFMG 530
Cdd:cd07201   161 GLIIESMLHDKKNDHKLSDQREAVSQGQNPLPIYLSLNVKDNLSTQDFREWVEFTPYEVGFLKYGAFIPAEDFGSEFFMG 240

                         250       260
                  ....*....|....*....|.
gi 2462542789 531 RLVKRIPESRICYMLASASSV 551
Cdd:cd07201   241 RLMKKLPESRICFLQGMWSSI 261
cPLA2_like cd00147
Cytosolic phospholipase A2, catalytic domain; hydrolyses arachidonyl phospholipids; Catalytic ...
 302-551 2.51e-121

Cytosolic phospholipase A2, catalytic domain; hydrolyses arachidonyl phospholipids; Catalytic domain of cytosolic phospholipase A2 (PLA2; EC 3.1.1.4) hydrolyzes the sn-2-acyl ester bond of phospholipids to release arachidonic acid. At the active site, cPLA2 contains a serine nucleophile through which the catalytic mechanism is initiated. The active site is partially covered by a solvent-accessible flexible lid. cPLA2 displays interfacial activation as it exists in both "closed lid" and "open lid" forms. Movement of the cPLA2 lid possibly exposes a greater hydrophobic surface and the active site. cPLA2 belongs to the alpha-beta hydrolase family which is identified by a characteristic nucleophile elbow with a consensus sequence of Sm-X-Nu-Sm (Sm = small residue, X = any residue and Nu = nucleophile). Calcium is required for cPLA2 to bind with membranes or phospholipids. Group IV cPLA2 includes six intercellular enzymes: cPLA2alpha, cPLA2beta, cPLA2gamma, cPLA2delta, cPLA2epsilon, and cPLA2zeta.


Pssm-ID: 132835 [Multi-domain]  Cd Length: 438  Bit Score: 366.19  E-value: 2.51e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 302 VRLGFSLCPAELEFLQKRKVVVAKALKQVLQLEEDLQEDEVPLIAIMATGGGTRSMTSMYGHLLGLQKLNLLDCASYITG 381
Cdd:cd00147     1 VRLASDLCDEEKEFLEKRRKVVAKALKKFLGLENDLNPDEVPVIAILGSGGGYRAMTGGAGALKALDEGGLLDCVTYLSG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 382 LSGATWTMATLYRDPDWSSKNLEPAIFEARRHVVKDKLPSLFPDQLRKFQEELRQRSQEGYRVTFTDFWGLLIETCLGDE 461
Cdd:cd00147    81 LSGSTWLMASLYSNPDWSQKDLDEAIEWLKRHVIKSPLLLFSPERLKYYAKELEEKKKAGFNVSLTDFWGLLLGYTLLKE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 462 RNECKLSDQRAALSCGQNPLPIYLTINVKDDV-SNQDFREWFEFSPYEVGLQKYGAFIPSELFGSEFFMGRLVKRIPESR 540
Cdd:cd00147   161 LTDSSLSDQREFVQNGQNPLPIYTALNVKPGEtSINDFATWFEFTPYEVGFPKYGAFIPTEYFGSKFFMGRLVKKIPEDR 240

                         250
                  ....*....|.
gi 2462542789 541 ICYMLASASSV 551
Cdd:cd00147   241 LGFLMGTWGSA 251
cPLA2_Grp-IVA cd07200
Group IVA cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group IVA cPLA2, an 85 ...
 303-538 7.05e-63

Group IVA cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group IVA cPLA2, an 85 kDa protein, consists of two domains: the regulatory C2 domain and the alpha/beta hydrolase PLA2 domain. Group IVA cPLA2 is also referred to as cPLA2-alpha. The catalytic domain of cytosolic phospholipase A2 (cPLA2; EC 3.1.1.4) hydrolyzes the sn-2-acyl ester bond of phospholipids to release arachidonic acid. At the active site, cPLA2 contains a serine nucleophile through which the catalytic mechanism is initiated. The active site is partially covered by a solvent-accessible flexible lid. cPLA2 displays interfacial activation as it exists in both "closed lid" and "open lid" forms. Movement of the cPLA2 lid possibly exposes a greater hydrophobic surface and the active site. cPLA2 belongs to the alpha-beta hydrolase family which is identified by a characteristic nucleophile elbow with a consensus sequence of Sm-X-Nu-Sm (Sm = small residue, X = any residue and Nu = nucleophile). Calcium is required for cPLA2 to bind with membranes or phospholipids. A calcium-dependent phospholipid binding domain resides in the N-terminal region of cPLA2; it is homologous to the C2 domain superfamily which is not included in this hierarchy. Includes PLA2G4A from chicken, human, and frog.


Pssm-ID: 132839  Cd Length: 505  Bit Score: 215.78  E-value: 7.05e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 303 RLGFSLCPAELEFLQKRKVVVAKALKQVLQLE--EDLQEDEVPLIAIMATGGGTRSMTSMYGHLLGLQKLNLLDCASYIT 380
Cdd:cd07200     2 RFSMALCDEEKEFRQARKMRVREALRKLLGEEgpKVTSLREVPVIALLGSGGGFRAMVGMSGAMKALYDSGVLDCATYVA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 381 GLSGATWTMATLYRDPDWSSKNLEPAIFEARRHVVKDKLPSLFPDQLRKFQEELRQRSQEGYRVTFTDFWGLLI-ETCLG 459
Cdd:cd07200    82 GLSGSTWYMSTLYSHPDFPEKGPGEINKELMRNVSSSPLLLLTPQLLKRYTEALWEKKSSGQPVTFTDFFGMLIgETLIK 161

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462542789 460 DERNEcKLSDQRAALSCGQNPLPIYLTINVKDDVSNQDFREWFEFSPYEVGLQKYGAFIPSELFGSEFFMGRLVKRIPE 538
Cdd:cd07200   162 ERMDT-KLSDLQEKVNDGQVPLPLFTCLHVKPDVSALMFHDWVEFSPYEIGMAKYGTFMSPDLFGSKFFMGFLAKKYPE 239
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 40-148 1.40e-58

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


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 191.71  E-value: 1.40e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  40 LLTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVtPDD 119
Cdd:cd04036     1 LLTVRVLRATNITKGDLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV-MDD 79

                          90       100
                  ....*....|....*....|....*....
gi 2462542789 120 HLLTVLYDLTKLCFRKKTHVKFPLNPQGM 148
Cdd:cd04036    80 HLGTVLFDVSKLKLGEKVRVTFSLNPQGK 108
cPLA2_Grp-IVC cd07202
Group IVC cytoplasmic phospholipase A2; catalytic domain; Ca-independent; Group IVC cPLA2, a ...
 301-546 1.04e-40

Group IVC cytoplasmic phospholipase A2; catalytic domain; Ca-independent; Group IVC cPLA2, a small 61 kDa protein, is a single domain alpha/beta hydrolase. It lacks a C2 domain; therefore, it has no Ca-dependence. Group IVC cPLA2 is also referred to as cPLA2-gamma. The cPLA2-gamma enzyme is predominantly found in cardiac and skeletal muscles, and to a lesser extent in the brain. Human cPLA2-gamma is approximately 30% identical to cPLA2-alpha. The catalytic domain of cytosolic phospholipase A2 (PLA2; EC 3.1.1.4) hydrolyzes the sn-2-acyl ester bond of phospholipids to release arachidonic acid. At the active site, cPLA2 contains a serine nucleophile through which the catalytic mechanism is initiated. The active site is partially covered by a solvent-accessible flexible lid. cPLA2 displays interfacial activation as it exists in both "closed lid" and "open lid" forms. Movement of the cPLA2 lid possibly exposes a greater hydrophobic surface and the active site. cPLA2 belongs to the alpha-beta hydrolase family which is identified by a characteristic nucleophile elbow with a consensus sequence of Sm-X-Nu-Sm (Sm = small residue, X = any residue and Nu = nucleophile). Includes PLA2G4C protein from human and Pla2g4c protein from mouse.


Pssm-ID: 132841 [Multi-domain]  Cd Length: 430  Bit Score: 153.40  E-value: 1.04e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 301 DVRLGFSLCPAELEFLQKRKVVVAKALKQVlqleeDLQEDEVPLIAIMATGGGTRSMTSMYGHLLGLQKLNLLDCASYIT 380
Cdd:cd07202     2 EVRIAPGLNKEEKAAVVKRRKDVLQSLQKL-----GINADKAPVIAVLGSGGGLRAMIACLGVLSELDKAGLLDCVTYLA 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 381 GLSGATWTMATLYRDPDWSSkNLEpaifearrhVVKDKLPSLFPDQLRKFQEELRQRSQEGYRVTF--TDFWGLLIETCL 458
Cdd:cd07202    77 GVSGSTWCMSSLYTEPDWST-KLQ---------TVEDELKRRLQKVSWDFAYALKKEIQAAKSDNFslTDFWAYLVVTTF 146

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 459 GDERNECKLSDQRAALSCGQNPLPIYLTINVKDDVSNQ--DFREWFEFSPYEVGLQKYGAFIPSELFGSEFFMGRLVKRI 536
Cdd:cd07202   147 TKELDESTLSDQRKQSEEGKDPYPIFAAIDKDLSEWKErkTGDPWFEFTPHEAGYPLPGAFVSTTHFGSKFENGKLVKQE 226

                         250
                  ....*....|
gi 2462542789 537 PESRICYMLA 546
Cdd:cd07202   227 PERDLLYLRA 236
PLAc smart00022
Cytoplasmic phospholipase A2, catalytic subunit; Cytosolic phospholipases A2 hydrolyse ...
 284-535 3.41e-38

Cytoplasmic phospholipase A2, catalytic subunit; Cytosolic phospholipases A2 hydrolyse arachidonyl phospholipids. Family includes phospholipases B isoforms.


Pssm-ID: 214474  Cd Length: 549  Bit Score: 148.73  E-value: 3.41e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  284 GESYELHMKSTPCPETLdVRLGFSLCPAELEFLQKRKVVVAKALKQVLQLE-------EDLQEDEVPLIAIMATGGGTRS 356
Cdd:smart00022  11 VDSYAPYNVSCPSDIPL-VRFSMGLSDNETEFLQKRKDYTNEAMKSFLGRAnsnfldsSLLNSSDVPKIAIAGSGGGFRA 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  357 MTS-------MYGHLLGLQKLNLLDCASYITGLSGATWTMATLYRDPDWSSKNLEPAIFE-ARRHVVKDKLPSLF--PDQ 426
Cdd:smart00022  90 MVGgagvlkaMDNRTDGHGLGGLLQSATYLAGLSGGTWLVGTLASNNFTPVKGPEEINSEwMFSVSINNPGINLLltAQF 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  427 LRKFQEELRQRSQEGYRVTFTDFWGLLIETCLGD--ERNECKLSDQRAA--LSCGQNPLPIYLTINVKDDVSNQDFREW- 501
Cdd:smart00022 170 YKSIVDAVWKKKDAGFNISLTDIWGRALSYNLFDslGGPNYTLSSLRDQekFQNAEMPLPIFVADGRKPGESVINFNDTv 249

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 2462542789  502 FEFSPYEVGL--QKYGAFIPSELFGSEFFMGRLVKR 535
Cdd:smart00022 250 FEFSPFEFGSwdPKLNAFMPPEYLGSKFFNGTPVKK 285
cPLA2_C2 pfam18695
Cytosolic phospholipases A2 C2-domain; Cytosolic phospholipases A2 (cPLA2s) consist of a ...
 180-292 2.63e-35

Cytosolic phospholipases A2 C2-domain; Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. In humans, the cPLA2 family contains six isoforms. Structural information of full length cPLA2alpha apo form, shows that it is composed of two domains; an N-terminal Ca2 + binding C2 domain and a C-terminal alpha/beta hydrolase core. This entry describes the N-terminal Ca2+ binding C2 domain which is composed of an eight-stranded antiparallel beta-sandwich consisting of two four-stranded beta-sheets. C2 domains are present in many lipid-binding proteins including Copines, CAPRI and Rabphilin-3A all of which are involved in membrane trafficking.


Pssm-ID: 465834  Cd Length: 111  Bit Score: 128.53  E-value: 2.63e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 180 CLEVHAQSRRRRKREKMKDLLVMVNESFENTQRVRPCLEPCCPTSacfqtaACFHYPKYFQSQVHVEVPKSHWSCGLCCR 259
Cdd:pfam18695   1 CLEVQVDSRGSKKEQGKKDLQLTVPGSYEGTQTISLGPEPGCPDP------FCFHYPKYWEPELHVELPKSSVLQSGWNS 74

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462542789 260 SRKKGPI--SQPLDCLSDGQVMTLPVGESYELHMK 292
Cdd:pfam18695  75 DLEKETSklTVPLKSLPLGQEVTVPLPEGQELHLR 109
PLA2_B pfam01735
Lysophospholipase catalytic domain; This family consists of Lysophospholipase / phospholipase ...
 345-535 1.39e-27

Lysophospholipase catalytic domain; This family consists of Lysophospholipase / phospholipase B EC:3.1.1.5 and cytosolic phospholipase A2 EC:3.1.4 which also has a C2 domain pfam00168. Phospholipase B enzymes catalyze the release of fatty acids from lysophsopholipids and are capable in vitro of hydrolysing all phospholipids extractable form yeast cells. Cytosolic phospholipase A2 associates with natural membranes in response to physiological increases in Ca2+ and selectively hydrolyses arachidonyl phospholipids, the aligned region corresponds the the carboxy-terminal Ca2+-independent catalytic domain of the protein as discussed in.


Pssm-ID: 366778  Cd Length: 490  Bit Score: 116.70  E-value: 1.39e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 345 IAIMATGGGTRSMTSMYG--------HLLGLQKLNLLDCASYITGLSGATWTMATLYRD-----PDWSSKNLEPAIfEAR 411
Cdd:pfam01735   1 IGIAGSGGGYRAMLGGAGvlaaldnrTDNETGLGGLLQSATYLAGLSGGSWLVGSLAVNnftsvQDFPDKPEDISI-WDL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 412 RHVVKDKLPSLFPDQLRKFQ---EELRQRSQEGYRVTFTDFWGLLIETCLGD---ERNECKLSDQRAA--LSCGQNPLPI 483
Cdd:pfam01735  80 NHSIFNPGGLNIPQNIKRYDdivDAVWKKKNAGFNVSLTDIWGRALSYTLIPslrGGPNYTWSSLRDAewFQNAEMPFPI 159

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2462542789 484 YLTINVKDDVSNQDFR-EWFEFSPYEVGL--QKYGAFIPSELFGSEFFMGRLVKR 535
Cdd:pfam01735 160 IVADGRKPGTTVINLNaTVFEFSPYEFGSwdPTLNSFTPTEYLGTKFFNGTPVKK 214
C2 pfam00168
C2 domain;
39-143 2.61e-21

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 88.92  E-value: 2.61e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  39 HLLTVRVIRMKNVRQADMLSQTDCFVSLWLpTASQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPD 118
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYL-LDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*
gi 2462542789 119 DHLLTVLYDLTKLCFRKKTHVKFPL 143
Cdd:pfam00168  80 DFIGEVRIPLSELDSGEGLDGWYPL 104
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 41-143 2.01e-20

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: 86.35  E-value: 2.01e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLptASQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPDDH 120
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSL--GGKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDF 78

                          90       100
                  ....*....|....*....|....
gi 2462542789 121 LLTVLYDLTKLCFRKKTHVK-FPL 143
Cdd:cd00030    79 LGEVEIPLSELLDSGKEGELwLPL 102
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 40-132 1.75e-19

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: 83.69  E-value: 1.75e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789   40 LLTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPDD 119
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                           90
                   ....*....|...
gi 2462542789  120 HLLTVLYDLTKLC 132
Cdd:smart00239  81 FIGQVTIPLSDLL 93
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 41-147 3.79e-13

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: 66.05  E-value: 3.79e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLPTasQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPDDH 120
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKFYLNG--EKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKDDL 78

                          90       100
                  ....*....|....*....|....*..
gi 2462542789 121 LLTVLYDLTKLCFRKKTHVKFPLNPQG 147
Cdd:cd04040    79 LGSAYIDLSDLEPEETTELTLPLDGQG 105
cPLA2_Fungal_PLB cd07203
Fungal Phospholipase B-like; cPLA2 GrpIVA homologs; catalytic domain; Fungal phospholipase B ...
 307-543 4.94e-13

Fungal Phospholipase B-like; cPLA2 GrpIVA homologs; catalytic domain; Fungal phospholipase B are Group IV cPLA2 homologs. Aspergillus PLA2 is Ca-dependent, yet it does not contain a C2 domain. PLB deacylates both sn-1 and sn-2 chains of phospholipids and are abundantly expressed in fungi. It shows lysophospholipase (lysoPL) and transacylase activities. The active site residues from cPLA2 are also conserved in PLB. Like cPLA2, PLB also has a consensus sequence of Sm-X-Nu-Sm (Sm = small residue, X = any residue and Nu = nucleophile). It includes PLB1 from Schizosaccharomyces pombe, PLB2 from Candida glabrata, and PLB3 from Saccharomyces cerevisiae. PLB1, PLB2, and PLB3 show PLB and lysoPL activities; PLB3 is specific for phosphoinositides.


Pssm-ID: 132842  Cd Length: 552  Bit Score: 72.01  E-value: 4.94e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 307 SLCPAELEFLQKRKVVVAKALKQVLQ---LEEDLQED-----EVPLIAIMATGGGTRSMT----------SMYGHLLGLQ 368
Cdd:cd07203    19 GLSTNEQEYLEKRRSITNSALKDFLSranLNGDDDLDsnnssNGPRIGIAVSGGGYRAMLtgagaiaamdNRTDNATEHG 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 369 KLNLLDCASYITGLSGATWTMATLYRDpDWSSKNlepaifearrHVVKDKL-----PSLFPDQLRKFQ---------EEL 434
Cdd:cd07203    99 LGGLLQSSTYLSGLSGGSWLVGSLASN-NFTSVQ----------DLLADSIwnldhSIFNPYGAAIVKtlnyytnlaNEV 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789 435 RQRSQEGYRVTFTDFWGLLIETCLGDERNE------CKLSDQRAALScGQNPLPIYLT---------INVKDDVsnqdfr 499
Cdd:cd07203   168 AQKKDAGFNVSLTDIWGRALSYQLFPALRGgpnltwSSIRNQSWFQN-AEMPFPIIVAdgrypgetiINLNATV------ 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 2462542789 500 ewFEFSPYEVGL--QKYGAFIPSELFGSEFFMGRlvkriPESRICY 543
Cdd:cd07203   241 --FEFTPYEFGSwdPSLNSFTPTEYLGTNVSNGV-----PPNGSCV 279
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 40-119 2.46e-12

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


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 64.66  E-value: 2.46e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  40 LLTVRVIRMKNVRQADMLSqTDCFVSLWLptaSQKKLRTRTISNCPNPEWNESFNFQIQSrVKNVLELSVCDEDTVTPDD 119
Cdd:cd04038     3 LLKVRVVRGTNLAVRDFTS-SDPYVVLTL---GNQKVKTRVIKKNLNPVWNEELTLSVPN-PMAPLKLEVFDKDTFSKDD 77
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 41-113 8.02e-11

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


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 59.60  E-value: 8.02e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLW-LPTASQK-KLRTRTISNCPNPEWNESFNF------QIQSRvknVLELSVCDE 112
Cdd:cd04035    17 LHCTIIRAKGLKAMDANGLSDPYVKLNlLPGASKAtKLRTKTVHKTRNPEFNETLTYygiteeDIQRK---TLRLLVLDE 93


                  .
gi 2462542789 113 D 113
Cdd:cd04035    94 D 94
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
41-147 2.33e-10

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 64.01  E-value: 2.33e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789   41 LTVRVIRMKNVRQADMLSQTDCFVSLWLptASQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPDDH 120
Cdd:COG5038   1042 LTIMLRSGENLPSSDENGYSDPFVKLFL--NEKSVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDL 1119

                           90       100
                   ....*....|....*....|....*..
gi 2462542789  121 LLTVLYDLTKLCFRKKTHVKFPLNPQG 147
Cdd:COG5038   1120 LGTAEIDLSKLEPGGTTNSNIPLDGKT 1146
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 39-119 3.84e-10

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


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 58.04  E-value: 3.84e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  39 HLLTVRVIRMKNVRQADMLSQTDCFVSLwLPTASQKKL-RTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTP 117
Cdd:cd04043     1 HLFTIRIVRAENLKADSSNGLSDPYVTL-VDTNGKRRIaKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGK 79


                  ..
gi 2462542789 118 DD 119
Cdd:cd04043    80 HD 81
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 35-121 4.19e-10

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: 57.98  E-value: 4.19e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  35 LSPCHL-----LTVRVIRMKNVRQADMLSQTDCFV--SLWLPTASQKKLRTRTISNCPNPEWNESFNFQI-QSRVKNV-L 105
Cdd:cd00276     5 LSLSYLptaerLTVVVLKARNLPPSDGKGLSDPYVkvSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVpAEQLEEVsL 84

                          90
                  ....*....|....*.
gi 2462542789 106 ELSVCDEDTVTPDDHL 121
Cdd:cd00276    85 VITVVDKDSVGRNEVI 100
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 40-121 8.44e-10

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: 56.54  E-value: 8.44e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  40 LLTVRVIRMKNVRQADMLSQTDCFVSLWLPTAsqkKLRTRTISNCPNPEWNESFNFQIQSrVKNVLELSVCDEDTVTPDD 119
Cdd:cd08377     2 FLQVKVIRASGLAAADIGGKSDPFCVLELVNA---RLQTHTIYKTLNPEWNKIFTFPIKD-IHDVLEVTVYDEDKDKKPE 77


                  ..
gi 2462542789 120 HL 121
Cdd:cd08377    78 FL 79
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 40-145 1.17e-09

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


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 56.11  E-value: 1.17e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  40 LLTVRVIRMKNVRQADMLSQTDCFVSLWLptaSQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPDD 119
Cdd:cd08376     1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRL---GNEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKKDE 77

                          90       100
                  ....*....|....*....|....*..
gi 2462542789 120 HLLTVLYDLTKLCfRKKTH-VKFPLNP 145
Cdd:cd08376    78 FIGRCEIDLSALP-REQTHsLELELED 103
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
 16-123 3.38e-08

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. 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: 175998 [Multi-domain]  Cd Length: 127  Bit Score: 52.26  E-value: 3.38e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  16 DPCQAEDSRPSAT----CALKEGLSPchlLTVRVIRMKNVRqADMLSQTDCFVSLWLptaSQKKLRTRTISNCPNPEWNE 91
Cdd:cd04032     4 DNCPCVCSSSPNVnsncCPTRRGLAT---LTVTVLRATGLW-GDYFTSTDGYVKVFF---GGQEKRTEVIWNNNNPRWNA 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2462542789  92 SFNFQ-IQSRVKNVLELSVCDEDTVTPDDHLLT 123
Cdd:cd04032    77 TFDFGsVELSPGGKLRFEVWDRDNGWDDDLLGT 109
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 41-119 5.23e-08

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: 52.04  E-value: 5.23e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQK--KLRTRTISNCPNPEWNESFNFQIQ-SRVKNV-LELSVCDEDTVT 116
Cdd:cd08405    17 ITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRveKKKTVIKKRTLNPVFNESFIFNIPlERLRETtLIITVMDKDRLS 96


                  ...
gi 2462542789 117 PDD 119
Cdd:cd08405    97 RND 99
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 41-119 1.11e-07

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 51.11  E-value: 1.11e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWL-PTAS-QKKLRTRTISNCPNPEWNESFNFQIQSRVKNV-LELSVCDEDTVTP 117
Cdd:cd04026    15 LTVEVREAKNLIPMDPNGLSDPYVKLKLiPDPKnETKQKTKTIKKTLNPVWNETFTFDLKPADKDRrLSIEVWDWDRTTR 94


                  ..
gi 2462542789 118 DD 119
Cdd:cd04026    95 ND 96
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 41-128 2.18e-07

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176024 [Multi-domain]  Cd Length: 121  Bit Score: 50.00  E-value: 2.18e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRqadmLSQTDCFVSLWLPTasqKKLRTRTISNCPNPEWNESFNF---QIQSrvkNVLELSVCDEDTVTp 117
Cdd:cd08378     2 LYVRVVKARGLP----ANSNDPVVEVKLGN---YKGSTKAIERTSNPEWNQVFAFskdRLQG---STLEVSVWDKDKAK- 70

                          90
                  ....*....|.
gi 2462542789 118 DDHLLTVLYDL 128
Cdd:cd08378    71 DDFLGGVCFDL 81
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 40-121 3.50e-07

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: 49.66  E-value: 3.50e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  40 LLTVRVIRMKNVRQADMLSQTD--CFVSLWLPTASQK--KLRTRTISNCPNPEWNESFNFQIQSRvKNVLELSVCDEDTV 115
Cdd:cd04033     1 ILRVKVLAGIDLAKKDIFGASDpyVKISLYDPDGNGEidSVQTKTIKKTLNPKWNEEFFFRVNPR-EHRLLFEVFDENRL 79


                  ....*.
gi 2462542789 116 TPDDHL 121
Cdd:cd04033    80 TRDDFL 85
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 41-121 3.89e-07

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


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 49.34  E-value: 3.89e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQKkLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPDDH 120
Cdd:cd04024     3 LRVHVVEAKDLAAKDRSGKGKSDPYAILSVGAQR-FKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKDY 81


                  .
gi 2462542789 121 L 121
Cdd:cd04024    82 L 82
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 41-139 7.29e-07

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: 48.07  E-value: 7.29e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQ-TDCFVSLWLPTASQKklrTRTISNCPNPEWN-ESFNFQIQSRV--KNVLELSVCDEDTVT 116
Cdd:cd08688     1 LKVRVVAARDLPVMDRSSDlTDAFVEVKFGSTTYK---TDVVKKSLNPVWNsEWFRFEVDDEElqDEPLQIRVMDHDTYS 77

                          90       100
                  ....*....|....*....|...
gi 2462542789 117 PDDHLLTVLYDLTKLCFRKKTHV 139
Cdd:cd08688    78 ANDAIGKVYIDLNPLLLKDSVSQ 100
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 41-121 7.44e-07

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: 48.50  E-value: 7.44e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWL-PTASQK-KLRTRTISNCPNPEWNESFNFQIQSR--VKNVLELSVCDEDTVT 116
Cdd:cd08384    15 LIVGIIRCVNLAAMDANGYSDPFVKLYLkPDAGKKsKHKTQVKKKTLNPEFNEEFFYDIKHSdlAKKTLEITVWDKDIGK 94


                  ....*
gi 2462542789 117 PDDHL 121
Cdd:cd08384    95 SNDYI 99
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 41-128 1.23e-06

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: 47.63  E-value: 1.23e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLW-LPTASQK-KLRTRTISNCPNPEWNESFNFQIQSR---VKNVLELSVCDEDTV 115
Cdd:cd04031    18 LIVTVLQARDLPPRDDGSLRNPYVKVYlLPDRSEKsKRRTKTVKKTLNPEWNQTFEYSNVRRetlKERTLEVTVWDYDRD 97

                          90
                  ....*....|...
gi 2462542789 116 TPDDHLLTVLYDL 128
Cdd:cd04031    98 GENDFLGEVVIDL 110
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 41-121 3.67e-06

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH 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. The members here have topology I.


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 46.61  E-value: 3.67e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTD--CFVSLwlptASQKKlRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPD 118
Cdd:cd08375    17 LMVVIVEGRDLKPCNSNGKSDpyCEVSM----GSQEH-KTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSPD 91


                  ...
gi 2462542789 119 DHL 121
Cdd:cd08375    92 DFL 94
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 41-131 6.19e-06

C2 domain first 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 45.62  E-value: 6.19e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQT-DCFVSLWLpTASQKKLRTRTISNCPNPEWNESFNFQIQSrVKNVLELSVCDEDTVTPDD 119
Cdd:cd04044     4 LAVTIKSARGLKGSDIIGGTvDPYVTFSI-SNRRELARTKVKKDTSNPVWNETKYILVNS-LTEPLNLTVYDFNDKRKDK 81

                          90
                  ....*....|..
gi 2462542789 120 HLLTVLYDLTKL 131
Cdd:cd04044    82 LIGTAEFDLSSL 93
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
 41-119 8.05e-06

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. 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: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 45.65  E-value: 8.05e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQ--KKLRTRTISNCPNPEWNESFNFQI-QSRVKNV-LELSVCDEDTVT 116
Cdd:cd08410    16 LNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLKliKTKKTSCMRGTIDPFYNESFSFKVpQEELENVsLVFTVYGHNVKS 95


                  ...
gi 2462542789 117 PDD 119
Cdd:cd08410    96 SND 98
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 25-121 3.25e-05

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 44.62  E-value: 3.25e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  25 PSATCALKEGLSPCHLLTVRVIRMKNVRQADMLSQTDCFV-SLWLPTASQK-KLRTRTISNCPNPEWNESFNF------Q 96
Cdd:cd04020    13 PESEGALKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVkCYLLPDKSKKsKQKTPVVKKSVNPVWNHTFVYdgvspeD 92

                          90       100
                  ....*....|....*....|....*
gi 2462542789  97 IQSRvknVLELSVCDEDTVTPDDHL 121
Cdd:cd04020    93 LSQA---CLELTVWDHDKLSSNDFL 114
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 37-131 3.90e-05

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


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 43.47  E-value: 3.90e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  37 PCHLLTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQKKLRTRTISNCPNPEWNESFNFQ------IQSRvknVLELSVC 110
Cdd:cd08386    14 QESTLTLKILKAVELPAKDFSGTSDPFVKIYLLPDKKHKLETKVKRKNLNPHWNETFLFEgfpyekLQQR---VLYLQVL 90

                          90       100
                  ....*....|....*....|.
gi 2462542789 111 DEDTVTPDDHLLTVLYDLTKL 131
Cdd:cd08386    91 DYDRFSRNDPIGEVSLPLNKV 111
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 39-119 4.29e-05

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: 43.57  E-value: 4.29e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  39 HLLTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQKKLRTRT-ISNC-PNPEWNESFNFQIQS-RVKNV-LELSVCDEDT 114
Cdd:cd08404    15 NRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRISKKKThVKKCtLNPVFNESFVFDIPSeELEDIsVEFLVLDSDR 94


                  ....*
gi 2462542789 115 VTPDD 119
Cdd:cd08404    95 VTKNE 99
Patatin_and_cPLA2 cd01819
Patatins and Phospholipases; Patatin-like phospholipase. This family consists of various ...
 347-393 4.74e-05

Patatins and Phospholipases; Patatin-like phospholipase. This family consists of various patatin glycoproteins from plants. The patatin protein accounts for up to 40% of the total soluble protein in potato tubers. Patatin is a storage protein, but it also has the enzymatic activity of a lipid acyl hydrolase, catalyzing the cleavage of fatty acids from membrane lipids. Members of this family have also been found in vertebrates. This family also includes the catalytic domain of cytosolic phospholipase A2 (PLA2; EC 3.1.1.4) hydrolyzes the sn-2-acyl ester bond of phospholipids to release arachidonic acid. At the active site, cPLA2 contains a serine nucleophile through which the catalytic mechanism is initiated. The active site is partially covered by a solvent-accessible flexible lid. cPLA2 displays interfacial activation as it exists in both "closed lid" and "open lid" forms.


Pssm-ID: 132836 [Multi-domain]  Cd Length: 155  Bit Score: 43.94  E-value: 4.74e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2462542789 347 IMATGGGTRSMtSMYGHLLGLQKLNLLDCASYITGLSGATWTMATLY 393
Cdd:cd01819     1 LSFSGGGFRGM-YHAGVLSALAERGLLDCVTYLAGTSGGAWVAATLY 46
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 74-130 6.82e-05

C2 domain third 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 third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 43.39  E-value: 6.82e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462542789  74 KKLRTRTISNCPNPEWNESFNFQIQ-----SRVKnvleLSVCDEDTVTPDDHLLTVLYDLTK 130
Cdd:cd04018    46 QKVKTSVKKNSYNPEWNEQIVFPEMfpplcERIK----IQIRDWDRVGNDDVIGTHFIDLSK 103
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 68-118 9.70e-05

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: 42.53  E-value: 9.70e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2462542789  68 LPTASQKKLRTRTIS-NCPNPEWNESFNFQIqsRVKN--VLELSVCDEDTVTPD 118
Cdd:cd00275    36 LPADDSAKFKTKVVKnNGFNPVWNETFEFDV--TVPElaFLRFVVYDEDSGDDD 87
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 41-119 1.90e-04

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: 41.62  E-value: 1.90e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFV--SLWLPTASQKKLRTRTISNCPNPEWNESFNFQIQS-RVKNV-LELSVCDEDTVT 116
Cdd:cd08402    17 LTVVILEAKNLKKMDVGGLSDPYVkiHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFeQIQKVhLIVTVLDYDRIG 96


                  ...
gi 2462542789 117 PDD 119
Cdd:cd08402    97 KND 99
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 41-121 5.62e-04

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


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 40.30  E-value: 5.62e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWL-PT---ASQKKLRTRTISNCPNPEWNESFNFQI---QSRVKN-VLELSVCDE 112
Cdd:cd04009    18 LRVEILNARNLLPLDSNGSSDPFVKVELlPRhlfPDVPTPKTQVKKKTLFPLFDESFEFNVppeQCSVEGaLLLFTVKDY 97


                  ....*....
gi 2462542789 113 DTVTPDDHL 121
Cdd:cd04009    98 DLLGSNDFE 106
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 41-122 7.54e-04

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


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 40.01  E-value: 7.54e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLptaSQKKLRTRTISNCPNPEWNESFNFQIQSRVKN---VLELSVCDEDTVTP 117
Cdd:cd04022     2 LVVEVVDAQDLMPKDGQGSSSAYVELDF---DGQKKRTRTKPKDLNPVWNEKLVFNVSDPSRLsnlVLEVYVYNDRRSGR 78


                  ....*
gi 2462542789 118 DDHLL 122
Cdd:cd04022    79 RRSFL 83
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 35-119 8.11e-04

C2 domain second repeat present in Synaptotagmins 3, 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 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. 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 second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 39.80  E-value: 8.11e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  35 LSPCHL-----LTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQ--KKLRTRTISNCPNPEWNESFNFQIQSR-VKNV-L 105
Cdd:cd08403     5 FSLCYLptagrLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRrlKKKKTSVKKNTLNPTYNEALVFDVPPEnVDNVsL 84

                          90
                  ....*....|....
gi 2462542789 106 ELSVCDEDTVTPDD 119
Cdd:cd08403    85 IIAVVDYDRVGHNE 98
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 41-144 1.02e-03

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 39.20  E-value: 1.02e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMlSQTDCFVSLWLPTASQK--KLRTRTISNCPNPEWNESFNF------QIQSRvknVLELSVCDE 112
Cdd:cd08381    15 LFVMVMHAKNLPLLDG-SDPDPYVKTYLLPDPQKttKRKTKVVRKTRNPTFNEMLVYdglpveDLQQR---VLQVSVWSH 90

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2462542789 113 DTVTPDDHLLTVLYDLTKLCFRKKTHVKFPLN 144
Cdd:cd08381    91 DSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 77-115 1.09e-03

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


Pssm-ID: 175982 [Multi-domain]  Cd Length: 158  Bit Score: 39.98  E-value: 1.09e-03
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 2462542789  77 RTRTISNCPNPEWNESFNFQIQSRVKNVlELSVCDEDTV 115
Cdd:cd04015    73 RTRVIENSENPVWNESFHIYCAHYASHV-EFTVKDNDVV 110
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
41-131 1.96e-03

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 41.28  E-value: 1.96e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789   41 LTVRVIRMKnVRQADMLSQTDCFVS------LWLPTASQKKLRTRTISNCPNPEWNESFNFQIQSrVKNVLELSVCDEDT 114
Cdd:COG5038    433 TAIGVVEVK-IKSAEGLKKSDSTINgtvdpyITVTFSDRVIGKTRVKKNTLNPVWNETFYILLNS-FTDPLNLSLYDFNS 510

                           90
                   ....*....|....*..
gi 2462542789  115 VTPDDHLLTVLYDLTKL 131
Cdd:COG5038    511 FKSDKVVGSTQLDLALL 527
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 42-131 2.40e-03

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


Pssm-ID: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 38.01  E-value: 2.40e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  42 TVRVI--RMKNVRQADM-LSQTDCFVSLWLPTASQKKLRTRTISNCPNPEWNES-FNFQIQSRVKNVLELSVC--DEDTV 115
Cdd:cd04041     2 VLVVTihRATDLPKADFgTGSSDPYVTASFAKFGKPLYSTRIIRKDLNPVWEETwFVLVTPDEVKAGERLSCRlwDSDRF 81

                          90
                  ....*....|....*.
gi 2462542789 116 TPDDHLLTVLYDLTKL 131
Cdd:cd04041    82 TADDRLGRVEIDLKEL 97
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 41-144 2.64e-03

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. 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: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 38.01  E-value: 2.64e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKN--VRQADMlSQTDCFVSLWL-P---TASQKKLRTRTisncPNPEWNESFNFQIQsrVKNVLELSVCdedt 114
Cdd:cd08390    16 LTVSLIKARNlpPRTKDV-AHCDPFVKVCLlPderRSLQSKVKRKT----QNPNFDETFVFQVS--FKELQRRTLR---- 84

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2462542789 115 vtpddhlLTVlYDLTKlcFRKKT---HVKFPLN 144
Cdd:cd08390    85 -------LSV-YDVDR--FSRHCiigHVLFPLK 107
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 41-113 2.69e-03

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: 38.32  E-value: 2.69e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLwlpTASQKKLRTRTISNCPNPEWNESFNFQIQS---RVKnvleLSVCDED 113
Cdd:cd04027     3 ISITVVCAQGLIAKDKTGTSDPYVTV---QVGKTKKRTKTIPQNLNPVWNEKFHFECHNssdRIK----VRVWDED 71
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
 41-118 2.93e-03

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. 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 synaptotagmin1. 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: 176063 [Multi-domain]  Cd Length: 118  Bit Score: 38.00  E-value: 2.93e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLptaSQKKLRTRTI-SNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTPD 118
Cdd:cd08681     3 LVVVVLKARNLPNKRKLDKQDPYCVLRI---GGVTKKTKTDfRGGQHPEWDEELRFEITEDKKPILKVAVFDDDKRKPD 78
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 41-113 2.97e-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: 38.01  E-value: 2.97e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQKKLRTRTISNCPNPEWNESFNFQI-QSRVKN-VLELSVCDED 113
Cdd:cd08385    18 LTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLNPVFNETFTFKVpYSELGNkTLVFSVYDFD 92
C2B_Synaptotagmin-15 cd08409
C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking ...
 39-100 3.00e-03

C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. 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: 176054 [Multi-domain]  Cd Length: 137  Bit Score: 38.47  E-value: 3.00e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462542789  39 HLLTVRVIRMKNVRQADmLSQTDCFV--SLWLPTASQKKLRTRTISNCPNPEWNESFNFQIQSR 100
Cdd:cd08409    15 NRLTVVVLRARGLRQLD-HAHTSVYVkvSLMIHNKVVKTKKTEVVDGAASPSFNESFSFKVTSR 77
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 41-119 3.03e-03

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


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 38.08  E-value: 3.03e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQKKLRTRtiSNCPNPEWNESFNFQI---QSRVKNVLELSVCDEDTVTP 117
Cdd:cd04049     3 LEVLLISAKGLQDTDFLGKIDPYVIIQCRTQERKSKVAK--GDGRNPEWNEKFKFTVeypGWGGDTKLILRIMDKDNFSD 80


                  ..
gi 2462542789 118 DD 119
Cdd:cd04049    81 DD 82
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 77-147 3.04e-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: 38.03  E-value: 3.04e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462542789  77 RTRTISNCPNPEWNESFNFQIQSrVKNVLELSVCDEDTVTPDDHLLTVLYDLTKLCFRKKTHVKFPL-NPQG 147
Cdd:cd04042    36 KSKTIYKNLNPVWDEKFTLPIED-VTQPLYIKVFDYDRGLTDDFMGSAFVDLSTLELNKPTEVKLKLeDPNS 106
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 75-118 3.19e-03

C2 domain first 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 38.00  E-value: 3.19e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2462542789  75 KLRTRTISNCPNPEWNESFNFQIQSRVKN--VLELSVCDEDTVTPD 118
Cdd:cd08373    27 KKKTRVLENELNPVWNETFEWPLAGSPDPdeSLEIVVKDYEKVGRN 72
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 38-147 6.81e-03

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: 37.08  E-value: 6.81e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  38 CHLLTVRVIRMKnvrqaDMLSQTDCFVSLWLptaSQKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLELSVCDEDTVTP 117
Cdd:cd04025     4 CHVLEARDLAPK-----DRNGTSDPFVRVFY---NGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSK 75

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2462542789 118 DDHLLTVLYDLTKLcfRKKTHVK--FPLNPQG 147
Cdd:cd04025    76 NDFLGKVVFSIQTL--QQAKQEEgwFRLLPDP 105
C2_C21orf25-like cd08678
C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...
 41-146 8.17e-03

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


Pssm-ID: 176060 [Multi-domain]  Cd Length: 126  Bit Score: 36.96  E-value: 8.17e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLPTasqKKLRTRTISNCPNPEWNESFNFQIQSRVKNVLeLSVCDeDTVTPDDH 120
Cdd:cd08678     1 LLVKNIKANGLSEAAGSSNPYCVLEMDEPP---QKYQSSTQKNTSNPFWDEHFLFELSPNSKELL-FEVYD-NGKKSDSK 75

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2462542789 121 LL---TVLYDLtklcFRK--KTHVKFPLNPQ 146
Cdd:cd08678    76 FLglaIVPFDE----LRKnpSGRQIFPLQGR 102
C2_Freud-1 cd08690
C2 domain found in 5' repressor element under dual repression binding protein-1 (Freud-1); ...
 41-98 9.16e-03

C2 domain found in 5' repressor element under dual repression binding protein-1 (Freud-1); Freud-1 is a novel calcium-regulated repressor that negatively regulates basal 5-HT1A receptor expression in neurons. It may also play a role in the altered regulation of 5-HT1A receptors associated with anxiety or major depression. Freud-1 contains two DM-14 basic repeats, a helix-loop-helix DNA binding domain, and a C2 domain. The Freud-1 C2 domain is thought to be calcium insensitive and it lacks several acidic residues that mediate calcium binding of the PKC C2 domain. In addition, it contains a poly-basic insert that is not present in calcium-dependent C2 domains and may function as a nuclear localization signal. 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: 176072 [Multi-domain]  Cd Length: 155  Bit Score: 37.29  E-value: 9.16e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462542789  41 LTVRVIRMKNVRQADMLSQTDCFVSLWLPTASQK--KLRTRTISNCPNPEWNESFNFQIQ 98
Cdd:cd08690     6 LTIVRCIGIPLPSGWNPKDLDTYVKFEFPYPNEEpqSGKTSTIKDTNSPEYNESFKLNIN 65
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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