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Conserved domains on  [gi|1677530579|ref|NP_001298122|]
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cytosolic phospholipase A2 isoform 2 [Homo sapiens]

Protein Classification

cPLA2 family C2 domain-containing protein( domain architecture ID 10134213)

cPLA2 (cytosolic phospholipase A2) family C2 domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
cPLA2_Grp-IVA cd07200
Group IVA cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group IVA cPLA2, an 85 ...
 114-670 0e+00

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: 876.01  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 114 VGEKKEVPFIFNQVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCATYVAGLSGSTWYMSTLYSHPDFPEKGPEEINE 193
Cdd:cd07200    30 LGEEGPKVTSLREVPVIALLGSGGGFRAMVGMSGAMKALYDSGVLDCATYVAGLSGSTWYMSTLYSHPDFPEKGPGEINK 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 194 ELMKNVSHNPLLLLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIGETLIHNRMNTTLSSLKEKVNTAQCPLPLFTCLH 273
Cdd:cd07200   110 ELMRNVSSSPLLLLTPQLLKRYTEALWEKKSSGQPVTFTDFFGMLIGETLIKERMDTKLSDLQEKVNDGQVPLPLFTCLH 189

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 274 VKPDVSELMFADWVEFSPYEIGMAKYGTFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNRVLGvsgsqsr 353
Cdd:cd07200   190 VKPDVSALMFHDWVEFSPYEIGMAKYGTFMSPDLFGSKFFMGFLAKKYPENPLHFLMGVWGSAFSILFNRVLG------- 262

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 354 gstmeeelenittkhivsndssdsddeshepkgtenedagsdyqsdnqaswihrmimalvsdsalFNTREGRAGKVHNFM 433
Cdd:cd07200   263 -----------------------------------------------------------------RNSREGRAGKVHNFM 277

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 434 LGLNLNTSYPLSPLSDFATqdsfddDELDAAVADPDEFERIYEPLDVKSKKIHVVDSGLTFNLPYPLILRPQRGVDLIIS 513
Cdd:cd07200   278 LGLNLNTSYPLSPLSDLAT------DEPEAAVADADEFERIYEPLDTKSKKIHVVDSGLTFNLPYPLILRPQRGVDLIIS 351

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 514 FDFSARPSDSSPPFKELLLAEKWAKMNKLPFPKIDPYVFDREGLKECYVFKPKNpdmEKDCPTIIHFVLANINFRKYRAP 593
Cdd:cd07200   352 FDFSARPSDSSPPFKELLLAEKWARMNGLPFPPIDFKVFDREGLKECYVFKPKN---DDDCPTVIHFVLCNINFRNLKAP 428

                         490       500       510       520       530       540       550
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1677530579 594 GVPRETEEEKEIADFDIFDDPESPFSTFNFQYPNQAFKRLHDLMHFNTLNNIDVIKEAMVESIEYRRQNPSRCSVSL 670
Cdd:cd07200   429 GVPRETEEEKEFANFDIFDDPETPFSTFNFQYPNQAFDRLHELMEFNTLNNIDVIKDAIRESIEKRRRNPSRCSVSL 505
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 20-129 4.75e-54

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: 180.92  E-value: 4.75e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  20 FTVVVLRATKVTKGafgDMLDTPDPYVELFISTTPDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVMD 99
Cdd:cd04036     2 LTVRVLRATNITKG---DLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMD 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1677530579 100 ETLGTATFTVSSMKVGEKKEVPFIFNQVPV 129
Cdd:cd04036    79 DHLGTVLFDVSKLKLGEKVRVTFSLNPQGK 108
 
Name Accession Description Interval E-value
cPLA2_Grp-IVA cd07200
Group IVA cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group IVA cPLA2, an 85 ...
 114-670 0e+00

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: 876.01  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 114 VGEKKEVPFIFNQVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCATYVAGLSGSTWYMSTLYSHPDFPEKGPEEINE 193
Cdd:cd07200    30 LGEEGPKVTSLREVPVIALLGSGGGFRAMVGMSGAMKALYDSGVLDCATYVAGLSGSTWYMSTLYSHPDFPEKGPGEINK 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 194 ELMKNVSHNPLLLLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIGETLIHNRMNTTLSSLKEKVNTAQCPLPLFTCLH 273
Cdd:cd07200   110 ELMRNVSSSPLLLLTPQLLKRYTEALWEKKSSGQPVTFTDFFGMLIGETLIKERMDTKLSDLQEKVNDGQVPLPLFTCLH 189

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 274 VKPDVSELMFADWVEFSPYEIGMAKYGTFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNRVLGvsgsqsr 353
Cdd:cd07200   190 VKPDVSALMFHDWVEFSPYEIGMAKYGTFMSPDLFGSKFFMGFLAKKYPENPLHFLMGVWGSAFSILFNRVLG------- 262

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 354 gstmeeelenittkhivsndssdsddeshepkgtenedagsdyqsdnqaswihrmimalvsdsalFNTREGRAGKVHNFM 433
Cdd:cd07200   263 -----------------------------------------------------------------RNSREGRAGKVHNFM 277

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 434 LGLNLNTSYPLSPLSDFATqdsfddDELDAAVADPDEFERIYEPLDVKSKKIHVVDSGLTFNLPYPLILRPQRGVDLIIS 513
Cdd:cd07200   278 LGLNLNTSYPLSPLSDLAT------DEPEAAVADADEFERIYEPLDTKSKKIHVVDSGLTFNLPYPLILRPQRGVDLIIS 351

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 514 FDFSARPSDSSPPFKELLLAEKWAKMNKLPFPKIDPYVFDREGLKECYVFKPKNpdmEKDCPTIIHFVLANINFRKYRAP 593
Cdd:cd07200   352 FDFSARPSDSSPPFKELLLAEKWARMNGLPFPPIDFKVFDREGLKECYVFKPKN---DDDCPTVIHFVLCNINFRNLKAP 428

                         490       500       510       520       530       540       550
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1677530579 594 GVPRETEEEKEIADFDIFDDPESPFSTFNFQYPNQAFKRLHDLMHFNTLNNIDVIKEAMVESIEYRRQNPSRCSVSL 670
Cdd:cd07200   429 GVPRETEEEKEFANFDIFDDPETPFSTFNFQYPNQAFDRLHELMEFNTLNNIDVIKDAIRESIEKRRRNPSRCSVSL 505
PLA2_B pfam01735
Lysophospholipase catalytic domain; This family consists of Lysophospholipase / phospholipase ...
 130-614 0e+00

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: 622.08  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 130 VAILGSGGGFRAMVGFSGVMKALY--------ESGILDCATYVAGLSGSTWYMSTL-----YSHPDFPEKgPEEINEELM 196
Cdd:pfam01735   1 IGIAGSGGGYRAMLGGAGVLAALDnrtdnetgLGGLLQSATYLAGLSGGSWLVGSLavnnfTSVQDFPDK-PEDISIWDL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 197 KNVSHNPLLLLTPQKVKRY---VESLWKKKSSGQPVTFTDIFGMLIGETLIH---NRMNTTLSSLK--EKVNTAQCPLPL 268
Cdd:pfam01735  80 NHSIFNPGGLNIPQNIKRYddiVDAVWKKKNAGFNVSLTDIWGRALSYTLIPslrGGPNYTWSSLRdaEWFQNAEMPFPI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 269 FTCLHVKPDVSELMF-ADWVEFSPYEIG--MAKYGTFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNRVL 345
Cdd:pfam01735 160 IVADGRKPGTTVINLnATVFEFSPYEFGswDPTLNSFTPTEYLGTKFFNGTPVKKGKCVPGFDNAGFVMGTSSTLFNQFL 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 346 GVSGSQSRgstmEEELENITTKHIVSNDSSDSDDESHEPkGTENEDAGSDYQSDNQaswihrmimALVSDSALFNTREGR 425
Cdd:pfam01735 240 LVINSTSS----LPSFLNIIIKHILKDLSEDSDDISQYP-PNPFQDANDINQNATN---------SIVDSDTLFLVDGGE 305

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 426 AGkvHNFMLGLNLNTSYPLSPLSDFATQDSFDDDELDaAVADPDEFERIYEPLDVKSKKIHVVDSGLTFNLpYPLILRP- 504
Cdd:pfam01735 306 DG--QNIPLWPLLQPERDVDVIFAVDNSADTDNDWPD-GVSLVDTYERQFEPLQVKGKKFPYVPDGNTFVN-LGLNTRPt 381

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 505 QRGVDLIISFDFSARPSDSSPPFKELLLAEKWAKMNKLPFPKIDPYVFDREGLKECyVFKPKNPDMEKDCPTIIHFVLAN 584
Cdd:pfam01735 382 FFGCDARNLTDLSARVSDSTPPLVVYLPNEPWSYMSNLSTFKISYNDSERQGLIEN-GFEAATQDNETDDPTFAHCVACA 460

                         490       500       510
                  ....*....|....*....|....*....|
gi 1677530579 585 INFRKYRAPGVPRETEEEKEIADFDIFDDP 614
Cdd:pfam01735 461 IIRRKLERLNITLPSECEQCFENYCWNGTV 490
PLAc smart00022
Cytoplasmic phospholipase A2, catalytic subunit; Cytosolic phospholipases A2 hydrolyse ...
 127-609 0e+00

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


Pssm-ID: 214474  Cd Length: 549  Bit Score: 616.36  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  127 VPVVAILGSGGGFRAMVGFSGVMKALYE-------SGILDCATYVAGLSGSTWYMSTLYSHPDFPEKGPEEINEELMKNV 199
Cdd:smart00022  75 VPKIAIAGSGGGFRAMVGGAGVLKAMDNrtdghglGGLLQSATYLAGLSGGTWLVGTLASNNFTPVKGPEEINSEWMFSV 154

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  200 SHN---PLLLLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIGETLIHN--RMNTTLSSLKE--KVNTAQCPLPLFTCL 272
Cdd:smart00022 155 SINnpgINLLLTAQFYKSIVDAVWKKKDAGFNISLTDIWGRALSYNLFDSlgGPNYTLSSLRDqeKFQNAEMPLPIFVAD 234

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  273 HVKPDVSELMFADWV-EFSPYEIGM--AKYGTFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNRVLGVsg 349
Cdd:smart00022 235 GRKPGESVINFNDTVfEFSPFEFGSwdPKLNAFMPPEYLGSKFFNGTPVKKGKCIPNFDNAGFIMGTSSSLFNRFLLV-- 312

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  350 sqSRGSTMEEELENITTKHIVSNDSSDSDDESHEPKGTENEDAgsdyqsdnqasWIHRMIMALVSDSALFNTREgragkv 429
Cdd:smart00022 313 --LSNSTMEESLIKIIIKHILKDLSSDSDDIAIYPPNPFKDDA-----------YVQRMLTNSLGDSDLLNLVD------ 373

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  430 hnfmlGLNLNTSYPLSPLsdFATQDSFDDDELDAAVADPDEFERIYEPLdVKSKKIHVVDSGLTFNLPYPLILRPQRGVD 509
Cdd:smart00022 374 -----GGEDGENIPLSPL--LQPERSVDVIFAVDASADTDEFWPNGSSL-VKTYERHVVDQGLTFNLPFPYVPDTQTFVN 445

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  510 LIISFDFSARPSDSS-----PPFKELLLAEKWAKMNKLPFPKIDPYVFDREGLK-ECYVFKPKNPDMEKDCptIIHFVLA 583
Cdd:smart00022 446 LGLSTKPTFFGCDSSnltyiPPLVVYLPNEKWAYNSNISTFKISYSVFEREGLIkNGYEFATVNNSTDDDC--FIHCVAC 523

                          490       500
                   ....*....|....*....|....*.
gi 1677530579  584 NINFRKYRAPGVPRETEEEKEIADFD 609
Cdd:smart00022 524 AIIFRKQEAPNVTLPSECSKCFYNYC 549
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 20-129 4.75e-54

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: 180.92  E-value: 4.75e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  20 FTVVVLRATKVTKGafgDMLDTPDPYVELFISTTPDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVMD 99
Cdd:cd04036     2 LTVRVLRATNITKG---DLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMD 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1677530579 100 ETLGTATFTVSSMKVGEKKEVPFIFNQVPV 129
Cdd:cd04036    79 DHLGTVLFDVSKLKLGEKVRVTFSLNPQGK 108
C2 pfam00168
C2 domain;
18-122 3.40e-17

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 77.36  E-value: 3.40e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  18 HKFTVVVLRATKVTKGafgDMLDTPDPYVELFIsTTPDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYV 97
Cdd:pfam00168   1 GRLTVTVIEAKNLPPK---DGNGTSDPYVKVYL-LDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRF 76

                          90       100
                  ....*....|....*....|....*.
gi 1677530579  98 -MDETLGTATFTVSSMKVGEKKEVPF 122
Cdd:pfam00168  77 gRDDFIGEVRIPLSELDSGEGLDGWY 102
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 19-120 3.84e-17

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: 77.14  E-value: 3.84e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579   19 KFTVVVLRATKVTKGafgDMLDTPDPYVELFISTTPDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVM 98
Cdd:smart00239   1 TLTVKIISARNLPPK---DKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFG 77

                           90       100
                   ....*....|....*....|...
gi 1677530579   99 -DETLGTATFTVSSMKVGEKKEV 120
Cdd:smart00239  78 rDDFIGQVTIPLSDLLLGGRHEK 100
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
43-115 1.02e-04

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 45.91  E-value: 1.02e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1677530579   43 DPYVELFISTTpdSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYV-MDETLGTATFTVSSMKVG 115
Cdd:COG5038   1062 DPFVKLFLNEK--SVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGeKNDLLGTAEIDLSKLEPG 1133
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
41-252 9.30e-04

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 42.82  E-value: 9.30e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579   41 TPDPYVElfISTTPDSRKRTRHFNNDINPVWNETFeFILDPNQENVLEITLMDANYVM-DETLGTATF---TVSSMKVGE 116
Cdd:COG5038    458 TVDPYIT--VTFSDRVIGKTRVKKNTLNPVWNETF-YILLNSFTDPLNLSLYDFNSFKsDKVVGSTQLdlaLLHQNPVKK 534

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  117 KKEVPFIFNQVPvVAILGSGGGFRAMVGFSGVMKALYE------SGI----LDCATYVAGLSGSTWYMSTlyshpdfpek 186
Cdd:COG5038    535 NELYEFLRNTKN-VGRLTYDLRFFPVIEDKKELKGSVEpledsnTGIlkvtLREVKALDELSSKKDNKSA---------- 603

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  187 gpeeineelmkNVSHNPLLLLTPQKVKRYVESLW----------KKKSSGQPVTFTDIFGMLIGET------LIHNRMNT 250
Cdd:COG5038    604 -----------ELYTNAKEVYSTGKLKFTNHPSWnlqynvlvtdRKNSSIKVVTFDVQSGKVIATEgstlpdLIDRTLDT 672


                   ..
gi 1677530579  251 TL 252
Cdd:COG5038    673 FL 674
 
Name Accession Description Interval E-value
cPLA2_Grp-IVA cd07200
Group IVA cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group IVA cPLA2, an 85 ...
 114-670 0e+00

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: 876.01  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 114 VGEKKEVPFIFNQVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCATYVAGLSGSTWYMSTLYSHPDFPEKGPEEINE 193
Cdd:cd07200    30 LGEEGPKVTSLREVPVIALLGSGGGFRAMVGMSGAMKALYDSGVLDCATYVAGLSGSTWYMSTLYSHPDFPEKGPGEINK 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 194 ELMKNVSHNPLLLLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIGETLIHNRMNTTLSSLKEKVNTAQCPLPLFTCLH 273
Cdd:cd07200   110 ELMRNVSSSPLLLLTPQLLKRYTEALWEKKSSGQPVTFTDFFGMLIGETLIKERMDTKLSDLQEKVNDGQVPLPLFTCLH 189

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 274 VKPDVSELMFADWVEFSPYEIGMAKYGTFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNRVLGvsgsqsr 353
Cdd:cd07200   190 VKPDVSALMFHDWVEFSPYEIGMAKYGTFMSPDLFGSKFFMGFLAKKYPENPLHFLMGVWGSAFSILFNRVLG------- 262

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 354 gstmeeelenittkhivsndssdsddeshepkgtenedagsdyqsdnqaswihrmimalvsdsalFNTREGRAGKVHNFM 433
Cdd:cd07200   263 -----------------------------------------------------------------RNSREGRAGKVHNFM 277

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 434 LGLNLNTSYPLSPLSDFATqdsfddDELDAAVADPDEFERIYEPLDVKSKKIHVVDSGLTFNLPYPLILRPQRGVDLIIS 513
Cdd:cd07200   278 LGLNLNTSYPLSPLSDLAT------DEPEAAVADADEFERIYEPLDTKSKKIHVVDSGLTFNLPYPLILRPQRGVDLIIS 351

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 514 FDFSARPSDSSPPFKELLLAEKWAKMNKLPFPKIDPYVFDREGLKECYVFKPKNpdmEKDCPTIIHFVLANINFRKYRAP 593
Cdd:cd07200   352 FDFSARPSDSSPPFKELLLAEKWARMNGLPFPPIDFKVFDREGLKECYVFKPKN---DDDCPTVIHFVLCNINFRNLKAP 428

                         490       500       510       520       530       540       550
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1677530579 594 GVPRETEEEKEIADFDIFDDPESPFSTFNFQYPNQAFKRLHDLMHFNTLNNIDVIKEAMVESIEYRRQNPSRCSVSL 670
Cdd:cd07200   429 GVPRETEEEKEFANFDIFDDPETPFSTFNFQYPNQAFDRLHELMEFNTLNNIDVIKDAIRESIEKRRRNPSRCSVSL 505
PLA2_B pfam01735
Lysophospholipase catalytic domain; This family consists of Lysophospholipase / phospholipase ...
 130-614 0e+00

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: 622.08  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 130 VAILGSGGGFRAMVGFSGVMKALY--------ESGILDCATYVAGLSGSTWYMSTL-----YSHPDFPEKgPEEINEELM 196
Cdd:pfam01735   1 IGIAGSGGGYRAMLGGAGVLAALDnrtdnetgLGGLLQSATYLAGLSGGSWLVGSLavnnfTSVQDFPDK-PEDISIWDL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 197 KNVSHNPLLLLTPQKVKRY---VESLWKKKSSGQPVTFTDIFGMLIGETLIH---NRMNTTLSSLK--EKVNTAQCPLPL 268
Cdd:pfam01735  80 NHSIFNPGGLNIPQNIKRYddiVDAVWKKKNAGFNVSLTDIWGRALSYTLIPslrGGPNYTWSSLRdaEWFQNAEMPFPI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 269 FTCLHVKPDVSELMF-ADWVEFSPYEIG--MAKYGTFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNRVL 345
Cdd:pfam01735 160 IVADGRKPGTTVINLnATVFEFSPYEFGswDPTLNSFTPTEYLGTKFFNGTPVKKGKCVPGFDNAGFVMGTSSTLFNQFL 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 346 GVSGSQSRgstmEEELENITTKHIVSNDSSDSDDESHEPkGTENEDAGSDYQSDNQaswihrmimALVSDSALFNTREGR 425
Cdd:pfam01735 240 LVINSTSS----LPSFLNIIIKHILKDLSEDSDDISQYP-PNPFQDANDINQNATN---------SIVDSDTLFLVDGGE 305

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 426 AGkvHNFMLGLNLNTSYPLSPLSDFATQDSFDDDELDaAVADPDEFERIYEPLDVKSKKIHVVDSGLTFNLpYPLILRP- 504
Cdd:pfam01735 306 DG--QNIPLWPLLQPERDVDVIFAVDNSADTDNDWPD-GVSLVDTYERQFEPLQVKGKKFPYVPDGNTFVN-LGLNTRPt 381

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 505 QRGVDLIISFDFSARPSDSSPPFKELLLAEKWAKMNKLPFPKIDPYVFDREGLKECyVFKPKNPDMEKDCPTIIHFVLAN 584
Cdd:pfam01735 382 FFGCDARNLTDLSARVSDSTPPLVVYLPNEPWSYMSNLSTFKISYNDSERQGLIEN-GFEAATQDNETDDPTFAHCVACA 460

                         490       500       510
                  ....*....|....*....|....*....|
gi 1677530579 585 INFRKYRAPGVPRETEEEKEIADFDIFDDP 614
Cdd:pfam01735 461 IIRRKLERLNITLPSECEQCFENYCWNGTV 490
PLAc smart00022
Cytoplasmic phospholipase A2, catalytic subunit; Cytosolic phospholipases A2 hydrolyse ...
 127-609 0e+00

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


Pssm-ID: 214474  Cd Length: 549  Bit Score: 616.36  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  127 VPVVAILGSGGGFRAMVGFSGVMKALYE-------SGILDCATYVAGLSGSTWYMSTLYSHPDFPEKGPEEINEELMKNV 199
Cdd:smart00022  75 VPKIAIAGSGGGFRAMVGGAGVLKAMDNrtdghglGGLLQSATYLAGLSGGTWLVGTLASNNFTPVKGPEEINSEWMFSV 154

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  200 SHN---PLLLLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIGETLIHN--RMNTTLSSLKE--KVNTAQCPLPLFTCL 272
Cdd:smart00022 155 SINnpgINLLLTAQFYKSIVDAVWKKKDAGFNISLTDIWGRALSYNLFDSlgGPNYTLSSLRDqeKFQNAEMPLPIFVAD 234

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  273 HVKPDVSELMFADWV-EFSPYEIGM--AKYGTFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNRVLGVsg 349
Cdd:smart00022 235 GRKPGESVINFNDTVfEFSPFEFGSwdPKLNAFMPPEYLGSKFFNGTPVKKGKCIPNFDNAGFIMGTSSSLFNRFLLV-- 312

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  350 sqSRGSTMEEELENITTKHIVSNDSSDSDDESHEPKGTENEDAgsdyqsdnqasWIHRMIMALVSDSALFNTREgragkv 429
Cdd:smart00022 313 --LSNSTMEESLIKIIIKHILKDLSSDSDDIAIYPPNPFKDDA-----------YVQRMLTNSLGDSDLLNLVD------ 373

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  430 hnfmlGLNLNTSYPLSPLsdFATQDSFDDDELDAAVADPDEFERIYEPLdVKSKKIHVVDSGLTFNLPYPLILRPQRGVD 509
Cdd:smart00022 374 -----GGEDGENIPLSPL--LQPERSVDVIFAVDASADTDEFWPNGSSL-VKTYERHVVDQGLTFNLPFPYVPDTQTFVN 445

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  510 LIISFDFSARPSDSS-----PPFKELLLAEKWAKMNKLPFPKIDPYVFDREGLK-ECYVFKPKNPDMEKDCptIIHFVLA 583
Cdd:smart00022 446 LGLSTKPTFFGCDSSnltyiPPLVVYLPNEKWAYNSNISTFKISYSVFEREGLIkNGYEFATVNNSTDDDC--FIHCVAC 523

                          490       500
                   ....*....|....*....|....*.
gi 1677530579  584 NINFRKYRAPGVPRETEEEKEIADFD 609
Cdd:smart00022 524 AIIFRKQEAPNVTLPSECSKCFYNYC 549
cPLA2_like cd00147
Cytosolic phospholipase A2, catalytic domain; hydrolyses arachidonyl phospholipids; Catalytic ...
 125-654 0e+00

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: 554.93  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 125 NQVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCATYVAGLSGSTWYMSTLYSHPDFPEKGPEEINEELMKNVSHNPL 204
Cdd:cd00147    39 DEVPVIAILGSGGGYRAMTGGAGALKALDEGGLLDCVTYLSGLSGSTWLMASLYSNPDWSQKDLDEAIEWLKRHVIKSPL 118

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 205 LLLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIGETLIHNRMNTTLSSLKEKVNTAQCPLPLFTCLHVKPDV-SELMF 283
Cdd:cd00147   119 LLFSPERLKYYAKELEEKKKAGFNVSLTDFWGLLLGYTLLKELTDSSLSDQREFVQNGQNPLPIYTALNVKPGEtSINDF 198

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 284 ADWVEFSPYEIGMAKYGTFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSILFNrvlgvsgsqsrgstmeeelen 363
Cdd:cd00147   199 ATWFEFTPYEVGFPKYGAFIPTEYFGSKFFMGRLVKKIPEDRLGFLMGTWGSAFSIILL--------------------- 257

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 364 ittkhivsndssdsddeshepkgtenedagsdyqsdnqaswihrmimalvsdsalfntregRAGKVHNFMLGLNLNTSYP 443
Cdd:cd00147   258 -------------------------------------------------------------DAGKYPNFFYGLNLHKSYL 276

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 444 lsplsdfatqdsfdddeldaavadpdefeRIYEPLDVKSKKIHVVDSGLTFN-LPYPLILRPQRGVDLIISFDFSARPSD 522
Cdd:cd00147   277 -----------------------------RSPNPLITSSDTLHLVDAGLDINnIPLPPLLRPERDVDVILSFDFSADDPD 327

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 523 SSPPFKELLLAEKWAKMNKLPFPKIDPYV-FDREGLKECYVFKPKNPDmekDCPTIIHFVLANINFRKYrapgvpretee 601
Cdd:cd00147   328 WPNGLKLVATYERQASSNGIPFPKIPDSVtFDNLGLKECYVFFGCDDP---DAPLVVYFPLVNDTFRKY----------- 393

                         490       500       510       520       530
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1677530579 602 ekeiadfdIFDDPESPFSTFNFQYPNQAFKRLHDLMHFNTLNNIDVIKEAMVE 654
Cdd:cd00147   394 --------DFDDPNSPYSTFNLSYTDEEFDRLLELAFYNVTNNKDTILQALRA 438
cPLA2_Grp-IVB-IVD-IVE-IVF cd07201
Group IVB, IVD, IVE, and IVF cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group ...
 126-661 1.16e-124

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: 381.30  E-value: 1.16e-124
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 126 QVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCATYVAGLSGSTWYMSTLYSHPDFPEKGPEEINEELMKNVSHNPLL 205
Cdd:cd07201    51 EVPVVAVMTTGGGTRALTSMYGSLLGLQKLGLLDCVSYITGLSGSTWTMATLYEDPNWSQKDLEGPIEEARKHVTKSKLG 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 206 LLTPQKVKRYVESLWKKKSSGQPVTFTDIFGMLIgETLIHN-RMNTTLSSLKEKVNTAQCPLPLFTCLHVKPDVSELMFA 284
Cdd:cd07201   131 CFSPERLKYYRQELSEREQEGHKVSFIDLWGLII-ESMLHDkKNDHKLSDQREAVSQGQNPLPIYLSLNVKDNLSTQDFR 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 285 DWVEFSPYEIGMAKYGTFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFSI-LFNRVLGVSGSQ------SRGSTM 357
Cdd:cd07201   210 EWVEFTPYEVGFLKYGAFIPAEDFGSEFFMGRLMKKLPESRICFLQGMWSSIFSLnLLDAWYLATGSEdfwhrwTRDKVN 289

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 358 EEELENITTKHivsndssdsddeshepkgtENEDAGSdyqSDNQASWIHRMIMALVSDSALfntregrAGKVHNFMLGLN 437
Cdd:cd07201   290 DIEDEPPLPPR-------------------PPERLTT---LLTPGGPLSQAFRDFLTSRPT-------VSQYFNFLRGLQ 340

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 438 LNTSYPLSPlsDFATqdsFDDDELDAAvadPDEferiyepLDVKSKKIHVVDSGLTFNLPYPLILRPQRGVDLIISFDFS 517
Cdd:cd07201   341 LHNDYLENK--GFST---WKDTHLDAF---PNQ-------LTPSEDHLCLVDTAFFINTSYPPLLRPERKVDVILSLNYS 405

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 518 arpsdSSPPFKELLLAEKWAKMNKLPFPKIDPYVFDREGLKECYVF-KPKNPdmekDCPTIIHFVLANINFRKYRAPGVP 596
Cdd:cd07201   406 -----LGSQFEPLKQASEYCSEQGIPFPKIELSPEDQENLKECYVFeDADNP----EAPIVLHFPLVNDTFRKYKAPGVE 476

                         490       500       510       520       530       540
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1677530579 597 RETEEEKEIADFDifDDPESPFSTFNFQYPNQAFKRLHDLMHFNTLNNIDVIKEAMVESIEYRRQ 661
Cdd:cd07201   477 RSPEEMAQGGVDV--SSSDSPYATRNLTYTEEDFDKLVKLTSYNVLNNKDLILQALRLAVERKKQ 539
cPLA2_Grp-IVC cd07202
Group IVC cytoplasmic phospholipase A2; catalytic domain; Ca-independent; Group IVC cPLA2, a ...
 125-585 9.54e-58

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: 201.55  E-value: 9.54e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 125 NQVPVVAILGSGGGFRAMVGFSGVMKALYESGILDCATYVAGLSGSTWYMSTLYSHPDFPEKgPEEINEELMknvshnpl 204
Cdd:cd07202    36 DKAPVIAVLGSGGGLRAMIACLGVLSELDKAGLLDCVTYLAGVSGSTWCMSSLYTEPDWSTK-LQTVEDELK-------- 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 205 llltpqkvKRYVESLWKKKSSGQPV---------TFTDIFGMLIGETLIHNRMNTTLSSLKEKVNTAQCPLPLFTCL-HV 274
Cdd:cd07202   107 --------RRLQKVSWDFAYALKKEiqaaksdnfSLTDFWAYLVVTTFTKELDESTLSDQRKQSEEGKDPYPIFAAIdKD 178

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 275 KPDVSELMFAD-WVEFSPYEIGMAKYGTFMAPDLFGSKFFMGTVVKKYEENPLHFLMGVWGSAFsilfnrvlgvsgsqsr 353
Cdd:cd07202   179 LSEWKERKTGDpWFEFTPHEAGYPLPGAFVSTTHFGSKFENGKLVKQEPERDLLYLRALWGSAL---------------- 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 354 gSTMEEELENITTkhivsndssdsddeshepkgtenedagsdyqsdnqASWIHrmimalvsdsalfntregraGKVHNFm 433
Cdd:cd07202   243 -ADGEEIAKYICM-----------------------------------SLWIW--------------------GTTYNF- 265

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 434 lglnlntsypLSPLSDfatqdsfdddeldaaVADPDEFEriyepldvKSKKIHVVDSGLTFNLPYPLILRPQRGVDLIIS 513
Cdd:cd07202   266 ----------LYKHGD---------------IADKPAMR--------SRETLHLMDAGLAINSPYPLVLPPVRNTDLILS 312

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1677530579 514 FDFSArpsdsSPPFKELLLAEKWAKMNKLPFPKIDPYVFDR--EGLKECYVFKPKNPdmekdcPTIIHFVLANI 585
Cdd:cd07202   313 FDFSE-----GDPFETIKDTAEYCRKHNIPFPQVDEAKLDQdaEAPKDFYVFKGENG------PVVMHFPLFNK 375
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 20-129 4.75e-54

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: 180.92  E-value: 4.75e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  20 FTVVVLRATKVTKGafgDMLDTPDPYVELFISTTPDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVMD 99
Cdd:cd04036     2 LTVRVLRATNITKG---DLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYVMD 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1677530579 100 ETLGTATFTVSSMKVGEKKEVPFIFNQVPV 129
Cdd:cd04036    79 DHLGTVLFDVSKLKLGEKVRVTFSLNPQGK 108
Patatin_and_cPLA2 cd01819
Patatins and Phospholipases; Patatin-like phospholipase. This family consists of various ...
 132-357 1.06e-23

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: 97.87  E-value: 1.06e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 132 ILGSGGGFRAMvGFSGVMKALYESGILDCATYVAGLSGSTWYMSTLYshpdfpekgpeeineelmknvshnplllltpqk 211
Cdd:cd01819     1 LSFSGGGFRGM-YHAGVLSALAERGLLDCVTYLAGTSGGAWVAATLY--------------------------------- 46

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 212 vkryveslwkkkssgqpvtftdifgmligetlihnrmnttlsslkekvntaqcplPLFTCLHVKPDVSE---LMFADWVE 288
Cdd:cd01819    47 -------------------------------------------------------PPSSSLDNKPRQSLeeaLSGKLWVS 71

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1677530579 289 FSPYEIGMAKYGTfmapdlfgskffmgTVVKKYEENPLHFLMGVWGSAFSILFNRVLGVSGSQSRGSTM 357
Cdd:cd01819    72 FTPVTAGENVLVS--------------RFVSKEELIRALFASGSWPSYFGLIPPAELYTSKSNLKEKGV 126
C2 pfam00168
C2 domain;
18-122 3.40e-17

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 77.36  E-value: 3.40e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  18 HKFTVVVLRATKVTKGafgDMLDTPDPYVELFIsTTPDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYV 97
Cdd:pfam00168   1 GRLTVTVIEAKNLPPK---DGNGTSDPYVKVYL-LDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRF 76

                          90       100
                  ....*....|....*....|....*.
gi 1677530579  98 -MDETLGTATFTVSSMKVGEKKEVPF 122
Cdd:pfam00168  77 gRDDFIGEVRIPLSELDSGEGLDGWY 102
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 19-120 3.84e-17

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: 77.14  E-value: 3.84e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579   19 KFTVVVLRATKVTKGafgDMLDTPDPYVELFISTTPDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVM 98
Cdd:smart00239   1 TLTVKIISARNLPPK---DKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFG 77

                           90       100
                   ....*....|....*....|...
gi 1677530579   99 -DETLGTATFTVSSMKVGEKKEV 120
Cdd:smart00239  78 rDDFIGQVTIPLSDLLLGGRHEK 100
cPLA2_Fungal_PLB cd07203
Fungal Phospholipase B-like; cPLA2 GrpIVA homologs; catalytic domain; Fungal phospholipase B ...
 125-525 3.71e-16

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: 82.03  E-value: 3.71e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 125 NQVPVVAILGSGGGFRAMVGFSGVMKAL---YES-------GILDCATYVAGLSGSTWYMSTLYSHpDFpeKGPEEINEE 194
Cdd:cd07203    60 SNGPRIGIAVSGGGYRAMLTGAGAIAAMdnrTDNatehglgGLLQSSTYLSGLSGGSWLVGSLASN-NF--TSVQDLLAD 136

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 195 LMKNVSHNpllLLTP------QKVKRYVE---SLWKKKSSGQPVTFTDIFGMLIGETLIHNRM---NTTLSSLKEKVN-- 260
Cdd:cd07203   137 SIWNLDHS---IFNPygaaivKTLNYYTNlanEVAQKKDAGFNVSLTDIWGRALSYQLFPALRggpNLTWSSIRNQSWfq 213

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 261 TAQCPLPLFTCLHVKP--DVSELMFADWvEFSPYEIgmakyGTFmAPDLFGskfFMgtvvkkyeenPLHFLmgvwGSAFS 338
Cdd:cd07203   214 NAEMPFPIIVADGRYPgeTIINLNATVF-EFTPYEF-----GSW-DPSLNS---FT----------PTEYL----GTNVS 269

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 339 ilfnrvlgvSGSQSRGSTMeeelenittkhivsndssdsddeshepKGTENedAGsdyqsdnqaswihrMIMAlvSDSAL 418
Cdd:cd07203   270 ---------NGVPPNGSCV---------------------------NGFDN--AG--------------FVMG--TSSTL 295

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579 419 FNtregragkvhNFMLGLNLNTSYplSPLSDFATQ--DSFDDDELDAAVADPDEFERiYEPLD-------VKSKKIHVVD 489
Cdd:cd07203   296 FN----------QFLLQINSTSSP--SFIKLIATGflLDILKENQDIASYIPNPFQG-YTYSNsngtnpiVDSDYLDLVD 362

                         410       420       430
                  ....*....|....*....|....*....|....*...
gi 1677530579 490 SGLTF-NLP-YPLiLRPQRGVDLIISFDFSARPSDSSP 525
Cdd:cd07203   363 GGEDGqNIPlWPL-LQPERDVDVIFAFDSSADTDYNWP 399
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 20-119 8.94e-15

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: 70.56  E-value: 8.94e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  20 FTVVVLRATKVTKGafgDMLDTPDPYVELFISttPDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVM- 98
Cdd:cd00030     1 LRVTVIEARNLPAK---DLNGKSDPYVKVSLG--GKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSk 75

                          90       100
                  ....*....|....*....|.
gi 1677530579  99 DETLGTATFTVSSMKVGEKKE 119
Cdd:cd00030    76 DDFLGEVEIPLSELLDSGKEG 96
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 35-115 1.15e-09

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: 56.78  E-value: 1.15e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  35 FGDMLDTPDPYVELFISTTP--DSRKRTRH--FNNDINPVWNETFEFILDPNQENVLEITLMDANYVMDETLGTATFTVS 110
Cdd:cd00275    18 KGDKGSIVDPYVEVEIHGLPadDSAKFKTKvvKNNGFNPVWNETFEFDVTVPELAFLRFVVYDEDSGDDDFLGQACLPLD 97


                  ....*
gi 1677530579 111 SMKVG 115
Cdd:cd00275    98 SLRQG 102
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 19-103 7.89e-09

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: 54.51  E-value: 7.89e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  19 KFTVVVLRATKVTKGafgDMLDTPDPYVELFIstTPDSR----KRTRHFNNDINPVWNETFEFILDPNQ-ENV-LEITLM 92
Cdd:cd00276    15 RLTVVVLKARNLPPS---DGKGLSDPYVKVSL--LQGGKklkkKKTSVKKGTLNPVFNEAFSFDVPAEQlEEVsLVITVV 89

                          90
                  ....*....|..
gi 1677530579  93 DANYVM-DETLG 103
Cdd:cd00276    90 DKDSVGrNEVIG 101
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 43-121 1.33e-08

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: 53.47  E-value: 1.33e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1677530579  43 DPYVELFISTTpdsRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVMDETLGTATFTVSsmkvgekkEVP 121
Cdd:cd08378    18 DPVVEVKLGNY---KGSTKAIERTSNPEWNQVFAFSKDRLQGSTLEVSVWDKDKAKDDFLGGVCFDLS--------EVP 85
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 22-129 2.61e-08

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: 52.56  E-value: 2.61e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  22 VVVLRATKVtKGaFGDMLDTPDPYVELFISTTPDSrKRTRHFNNDINPVWNETFEFILDpNQENVLEITLMDANYVM-DE 100
Cdd:cd04044     6 VTIKSARGL-KG-SDIIGGTVDPYVTFSISNRREL-ARTKVKKDTSNPVWNETKYILVN-SLTEPLNLTVYDFNDKRkDK 81

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1677530579 101 TLGTATFTVSSM---KVGEKKEVPFIFNQVPV 129
Cdd:cd04044    82 LIGTAEFDLSSLlqnPEQENLTKNLLRNGKPV 113
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 15-91 5.75e-08

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 51.89  E-value: 5.75e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  15 QYS---HKFTVVVLRATKVTKGafgDMLDTPDPYVELFIstTPD----SRKRTRHFNNDINPVWNETFEFI--LDPNQEN 85
Cdd:cd04030    10 RYSsqrQKLIVTVHKCRNLPPC---DSSDIPDPYVRLYL--LPDksksTRRKTSVKKDNLNPVFDETFEFPvsLEELKRR 84


                  ....*.
gi 1677530579  86 VLEITL 91
Cdd:cd04030    85 TLDVAV 90
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 41-111 1.60e-07

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


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 50.37  E-value: 1.60e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1677530579  41 TPDPYVELFISTTpdsRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVMDETLGTATFTVSS 111
Cdd:cd08391    27 KSDPYVIVRVGAQ---TFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDEDPDKDDFLGRLSIDLGS 94
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 35-129 2.39e-07

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. 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: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 49.92  E-value: 2.39e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  35 FGDMldtpDPYVELFISttPDSRKRTR-HFNNDINPVWNETFEFILDPN----QENVLEITLMDANYVM-DETLGTATFT 108
Cdd:cd04051    18 FGKM----KVYAVVWID--PSHKQSTPvDRDGGTNPTWNETLRFPLDERllqqGRLALTIEVYCERPSLgDKLIGEVRVP 91

                          90       100
                  ....*....|....*....|.
gi 1677530579 109 VSSMKVGEKKEVPFIFNQVPV 129
Cdd:cd04051    92 LKDLLDGASPAGELRFLSYQL 112
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 14-93 6.22e-07

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: 48.78  E-value: 6.22e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  14 HQYSHKFTVVVLRATKVTKGAFGDMldtPDPYVELFI--STTPDSRKRTRHFNNDINPVWNETFEF---ILDPNQENVLE 88
Cdd:cd04031    12 DKVTSQLIVTVLQARDLPPRDDGSL---RNPYVKVYLlpDRSEKSKRRTKTVKKTLNPEWNQTFEYsnvRRETLKERTLE 88


                  ....*
gi 1677530579  89 ITLMD 93
Cdd:cd04031    89 VTVWD 93
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 23-106 1.17e-06

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: 48.02  E-value: 1.17e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  23 VVLRATKVTkGAFGdmldTPDPYVELfisTTPDSRKRTRHFNNDINPVWNETFEF----ILDPNQenVLEITLMDAN-YV 97
Cdd:cd08373     1 LVVSLKNLP-GLKG----KGDRIAKV---TFRGVKKKTRVLENELNPVWNETFEWplagSPDPDE--SLEIVVKDYEkVG 70


                  ....*....
gi 1677530579  98 MDETLGTAT 106
Cdd:cd08373    71 RNRLIGSAT 79
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 40-121 2.14e-06

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: 47.42  E-value: 2.14e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  40 DTPDPYVelfISTTPDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVM-DETLGTATFTVSSMKVGEKK 118
Cdd:cd04024    22 GKSDPYA---ILSVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAgKDYLGEFDIALEEVFADGKT 98


                  ...
gi 1677530579 119 EVP 121
Cdd:cd04024    99 GQS 101
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 43-120 3.07e-06

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: 46.41  E-value: 3.07e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  43 DPYVELFISTTP----DSRKRTrhfnndINPVWNETFEFILDPNQENVLEITLMDANYV-MDETLGTATFTVSSMKVGEK 117
Cdd:cd04040    21 DPFVKFYLNGEKvfktKTIKKT------LNPVWNESFEVPVPSRVRAVLKVEVYDWDRGgKDDLLGSAYIDLSDLEPEET 94


                  ...
gi 1677530579 118 KEV 120
Cdd:cd04040    95 TEL 97
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 22-107 3.25e-06

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: 47.32  E-value: 3.25e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  22 VVVLRATKVtkgAFGDMLdTPDPYVelfISTTPDSRKRTRHFNNDINPVWNETFEFILdPNQENVLEITLMDAN-YVMDE 100
Cdd:cd04038     6 VRVVRGTNL---AVRDFT-SSDPYV---VLTLGNQKVKTRVIKKNLNPVWNEELTLSV-PNPMAPLKLEVFDKDtFSKDD 77


                  ....*..
gi 1677530579 101 TLGTATF 107
Cdd:cd04038    78 SMGEAEI 84
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 18-115 1.15e-05

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: 45.33  E-value: 1.15e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  18 HKFTVVVLRATKVtKGAfgDMLDTPDPYVELFISTTPDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYV 97
Cdd:cd04043     1 HLFTIRIVRAENL-KAD--SSNGLSDPYVTLVDTNGKRRIAKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFV 77

                          90
                  ....*....|....*....
gi 1677530579  98 -MDETLGTATFTVSSMKVG 115
Cdd:cd04043    78 gKHDLCGRASLKLDPKRFG 96
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 37-118 1.41e-05

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


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 44.97  E-value: 1.41e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  37 DMLDTPDPYVELFISTT--PDSRKRTRHFNNDINPVWNETFEF--ILDPNQEN-VLEITLMDANYVMDETLGTATFTVSS 111
Cdd:cd04035    31 DANGLSDPYVKLNLLPGasKATKLRTKTVHKTRNPEFNETLTYygITEEDIQRkTLRLLVLDEDRFGNDFLGETRIPLKK 110


                  ....*..
gi 1677530579 112 MKVGEKK 118
Cdd:cd04035   111 LKPNQTK 117
C2_NEDL1-like cd08691
C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 ...
 20-93 1.57e-05

C2 domain present in NEDL1 (NEDD4-like ubiquitin protein ligase-1); NEDL1 (AKA HECW1(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1)) is a newly identified HECT-type E3 ubiquitin protein ligase highly expressed in favorable neuroblastomas. In vertebrates it is found primarily in neuronal tissues, including the spinal cord. NEDL1 is thought to normally function in the quality control of cellular proteins by eliminating misfolded proteins. This is thought to be accomplished via a mechanism analogous to that of ER-associated degradation by forming tight complexes and aggregating misfolded proteins that have escaped ubiquitin-mediated degradation. NEDL1, is composed of a C2 domain, two WW domains, and a ubiquitin ligase Hect 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.


Pssm-ID: 176073 [Multi-domain]  Cd Length: 137  Bit Score: 45.09  E-value: 1.57e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  20 FTVVVLRATKVTKGAFGDmldtPDPYVELFISTTPDS----------RKRTRHFNNDINPVW-NETFEFILDPNqeNVLE 88
Cdd:cd08691     3 FSLSGLQARNLKKGMFFN----PDPYVKISIQPGKRHifpalphhgqECRTSIVENTINPVWhREQFVFVGLPT--DVLE 76


                  ....*
gi 1677530579  89 ITLMD 93
Cdd:cd08691    77 IEVKD 81
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 21-93 1.70e-05

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: 45.10  E-value: 1.70e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1677530579  21 TVVVLRATKVtkgAFGDMLDTPDPYVELFIsTTPDSR---KRTRHFNNDINPVWNETFEF--ILDPNQENVLEITLMD 93
Cdd:cd08405    18 TVNIIKARNL---KAMDINGTSDPYVKVWL-MYKDKRvekKKTVIKKRTLNPVFNESFIFniPLERLRETTLIITVMD 91
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 37-90 2.51e-05

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: 44.25  E-value: 2.51e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1677530579  37 DMLDTPDPYVELFISttpDSRKRTRHFNNDINPVWNETFEF-ILDPN--QENVLEIT 90
Cdd:cd04022    16 DGQGSSSAYVELDFD---GQKKRTRTKPKDLNPVWNEKLVFnVSDPSrlSNLVLEVY 69
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 37-110 2.60e-05

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


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 43.75  E-value: 2.60e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1677530579  37 DMLDTPDPYVELFISTTPDSRKRTRHFNNdiNPVWNETFEFILdPNQEN-VLEITLMDANYVMDETLGTATFTVS 110
Cdd:cd04052     8 SKTGLLSPYAELYLNGKLVYTTRVKKKTN--NPSWNASTEFLV-TDRRKsRVTVVVKDDRDRHDPVLGSVSISLN 79
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 43-137 2.86e-05

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


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 43.73  E-value: 2.86e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  43 DPYVELFISTTPdsRKRTRHFNNDINPVWNETFEF-ILDPNQenVLEITLMDANYV-MDETLGTATFTVSSM--KVGEKK 118
Cdd:cd04045    23 DPYVRVLVNGIV--KGRTVTISNTLNPVWDEVLYVpVTSPNQ--KITLEVMDYEKVgKDRSLGSVEINVSDLikKNEDGK 98

                          90
                  ....*....|....*....
gi 1677530579 119 EVPFIFNQVPVVAILGSGG 137
Cdd:cd04045    99 YVEYDDEEERLKRLLSLKG 117
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
 21-77 2.88e-05

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: 44.17  E-value: 2.88e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1677530579  21 TVVVLRATkvtkGAFGDMLDTPDPYVELFISttpDSRKRTRHFNNDINPVWNETFEF 77
Cdd:cd04032    31 TVTVLRAT----GLWGDYFTSTDGYVKVFFG---GQEKRTEVIWNNNNPRWNATFDF 80
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 20-118 3.51e-05

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: 43.40  E-value: 3.51e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  20 FTVVVL--RATKVTKGAFGdmLDTPDPYVELFISTTPDSRKRTRHFNNDINPVWNETFEFILDPNQENV---LEITLMDA 94
Cdd:cd04041     1 GVLVVTihRATDLPKADFG--TGSSDPYVTASFAKFGKPLYSTRIIRKDLNPVWEETWFVLVTPDEVKAgerLSCRLWDS 78

                          90       100
                  ....*....|....*....|....*
gi 1677530579  95 NYV-MDETLGTATFTVSSMKVGEKK 118
Cdd:cd04041    79 DRFtADDRLGRVEIDLKELIEDRNW 103
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 17-112 4.94e-05

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc 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.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 43.42  E-value: 4.94e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  17 SHKFTVVVLRAT-KVTKGAFGdmldtPDPYVELFISTTPdsRKRTRHFNNDINPVWNETFEFILDPNqeNVLEITLMD-A 94
Cdd:cd04021     1 KSQLQITVESAKlKSNSKSFK-----PDPYVEVTVDGQP--PKKTEVSKKTSNPKWNEHFTVLVTPQ--STLEFKVWShH 71

                          90
                  ....*....|....*...
gi 1677530579  95 NYVMDETLGTATFTVSSM 112
Cdd:cd04021    72 TLKADVLLGEASLDLSDI 89
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 37-77 7.63e-05

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


Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 42.94  E-value: 7.63e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1677530579  37 DMLDTPDPYVELFISTTpdsRKRTRHFNNDINPVWNETFEF 77
Cdd:cd04027    17 DKTGTSDPYVTVQVGKT---KKRTKTIPQNLNPVWNEKFHF 54
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
43-115 1.02e-04

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 45.91  E-value: 1.02e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1677530579   43 DPYVELFISTTpdSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYV-MDETLGTATFTVSSMKVG 115
Cdd:COG5038   1062 DPFVKLFLNEK--SVYKTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGeKNDLLGTAEIDLSKLEPG 1133
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 19-93 1.55e-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: 42.39  E-value: 1.55e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1677530579  19 KFTVVVLRATKVTKGafgDMLDTPDPYVE--LFISTTPDSRKRTRHFNNDINPVWNETFEFILDPNQ-ENV-LEITLMD 93
Cdd:cd08402    16 KLTVVILEAKNLKKM---DVGGLSDPYVKihLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQiQKVhLIVTVLD 91
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 43-85 1.89e-04

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: 41.86  E-value: 1.89e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1677530579  43 DPYVELFISTTP--DSRKRTRHFNNDINPVWNETFEFILDPNQEN 85
Cdd:cd04026    35 DPYVKLKLIPDPknETKQKTKTIKKTLNPVWNETFTFDLKPADKD 79
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 37-77 4.80e-04

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: 40.33  E-value: 4.80e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1677530579  37 DMLDTPDPYVELFIstTPDSRKR--TRHFNNDINPVWNETFEF 77
Cdd:cd08385    32 DMGGTSDPYVKVYL--LPDKKKKfeTKVHRKTLNPVFNETFTF 72
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 17-93 7.04e-04

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: 40.49  E-value: 7.04e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  17 SHKFTVVVLRATKVTKGafgDMLDTPDPYVELFISTTPD--SRKRTRHFNNDINPVWNETFEFIL--DPNQENVLEITLM 92
Cdd:cd08404    14 TNRLTVVVLKARHLPKM---DVSGLADPYVKVNLYYGKKriSKKKTHVKKCTLNPVFNESFVFDIpsEELEDISVEFLVL 90


                  .
gi 1677530579  93 D 93
Cdd:cd08404    91 D 91
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 34-79 8.13e-04

C2 domain first repeat present in Synaptotagmin-like proteins; 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. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 39.93  E-value: 8.13e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1677530579  34 AFGDML-DTPDPYVELFIstTPD----SRKRTRHFNNDINPVWNETFEFIL 79
Cdd:cd08521    27 AYADEKkKRSNPYVKVYL--LPDkskqSKRKTSVKKNTTNPVFNETLKYHI 75
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 43-93 8.98e-04

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 40.02  E-value: 8.98e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1677530579  43 DPYVELFIstTPDSRKRTRHFNN----DINPVWNETFEFILDPNQ--ENVLEITLMD 93
Cdd:cd08384    35 DPFVKLYL--KPDAGKKSKHKTQvkkkTLNPEFNEEFFYDIKHSDlaKKTLEITVWD 89
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
41-252 9.30e-04

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 42.82  E-value: 9.30e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579   41 TPDPYVElfISTTPDSRKRTRHFNNDINPVWNETFeFILDPNQENVLEITLMDANYVM-DETLGTATF---TVSSMKVGE 116
Cdd:COG5038    458 TVDPYIT--VTFSDRVIGKTRVKKNTLNPVWNETF-YILLNSFTDPLNLSLYDFNSFKsDKVVGSTQLdlaLLHQNPVKK 534

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  117 KKEVPFIFNQVPvVAILGSGGGFRAMVGFSGVMKALYE------SGI----LDCATYVAGLSGSTWYMSTlyshpdfpek 186
Cdd:COG5038    535 NELYEFLRNTKN-VGRLTYDLRFFPVIEDKKELKGSVEpledsnTGIlkvtLREVKALDELSSKKDNKSA---------- 603

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  187 gpeeineelmkNVSHNPLLLLTPQKVKRYVESLW----------KKKSSGQPVTFTDIFGMLIGET------LIHNRMNT 250
Cdd:COG5038    604 -----------ELYTNAKEVYSTGKLKFTNHPSWnlqynvlvtdRKNSSIKVVTFDVQSGKVIATEgstlpdLIDRTLDT 672


                   ..
gi 1677530579  251 TL 252
Cdd:COG5038    673 FL 674
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 40-93 1.53e-03

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: 40.00  E-value: 1.53e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1677530579  40 DTPDPYVELFIstTPD----SRKRTRHFNNDINPVWNETFEF---ILDPNQENVLEITLMD 93
Cdd:cd04020    46 GTSDSFVKCYL--LPDkskkSKQKTPVVKKSVNPVWNHTFVYdgvSPEDLSQACLELTVWD 104
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 22-95 1.73e-03

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: 39.26  E-value: 1.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  22 VVVLRATKVTKGafgDMLDTPDPYVELFI-----STTPDS-----RKRTRhfnndiNPVWNETFEFILDPnQENVLEITL 91
Cdd:cd04033     4 VKVLAGIDLAKK---DIFGASDPYVKISLydpdgNGEIDSvqtktIKKTL------NPKWNEEFFFRVNP-REHRLLFEV 73


                  ....
gi 1677530579  92 MDAN 95
Cdd:cd04033    74 FDEN 77
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
 41-120 2.62e-03

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A 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: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 38.49  E-value: 2.62e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  41 TPDPYVELFISTTPDSRKRTRHFNNDINPVWNETFEFI-LDPNQenVLEITLMDA-----NYVMDETLGTATFTVSSMKV 114
Cdd:cd08388    37 TSDPYVKLQLLPEKEHKVKTRVLRKTRNPVYDETFTFYgIPYNQ--LQDLSLHFAvlsfdRYSRDDVIGEVVCPLAGADL 114


                  ....*.
gi 1677530579 115 GEKKEV 120
Cdd:cd08388   115 LNEGEL 120
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 16-77 3.05e-03

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


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 38.08  E-value: 3.05e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1677530579  16 YSHKFTVVVLRATKVTKGAFGDMLDTPDPYVELFISTTPDSRKRTRHFNNDINPVWNETFEF 77
Cdd:cd08386    11 YDFQESTLTLKILKAVELPAKDFSGTSDPFVKIYLLPDKKHKLETKVKRKNLNPHWNETFLF 72
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 37-94 5.13e-03

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). 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 type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 37.67  E-value: 5.13e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1677530579  37 DMLDTPDPYVELFI-----STTPDSRKRtrhfnndINPVWNETFEFILDPNqeNVLEITLMDA 94
Cdd:cd08382    16 DLFRLPDPFAVITVdggqtHSTDVAKKT-------LDPKWNEHFDLTVGPS--SIITIQVFDQ 69
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 42-111 5.60e-03

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: 37.24  E-value: 5.60e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1677530579  42 PDPYVELFISttpDSRKRTRHFNNDINPVWNETFEFILDPNQENVLEITLMDANYVM-DETLGTATFTVSS 111
Cdd:cd08376    21 SDPYVKFRLG---NEKYKSKVCSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGKkDEFIGRCEIDLSA 88
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 29-104 6.10e-03

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: 38.00  E-value: 6.10e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1677530579  29 KVTKGAFGDMLDTPDPYVELFISttpDSRKRTRHFNNDINPVWNETFEF-ILDPNQENVLEITLMD-ANYVMDETLGT 104
Cdd:cd04018    22 NVKKAFLGEKKELVDPYVEVSFA---GQKVKTSVKKNSYNPEWNEQIVFpEMFPPLCERIKIQIRDwDRVGNDDVIGT 96
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 20-118 6.84e-03

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


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 36.89  E-value: 6.84e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  20 FTVVVLRATKVtkgAFGDMLDTPDPYVELFISttpDSRKRTRHFNNDINPVWNETFEF-ILDPNQenVLEITLMDANYVM 98
Cdd:cd08377     3 LQVKVIRASGL---AAADIGGKSDPFCVLELV---NARLQTHTIYKTLNPEWNKIFTFpIKDIHD--VLEVTVYDEDKDK 74

                          90       100
                  ....*....|....*....|.
gi 1677530579  99 D-ETLGTATFTVSSMKVGEKK 118
Cdd:cd08377    75 KpEFLGKVAIPLLSIKNGERK 95
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 40-112 8.05e-03

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 36.52  E-value: 8.05e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1677530579  40 DTPDPYVEL----FISTTPDSRKrtrhfnnDINPVWN-ETFEFILDPN--QENVLEITLMDAN-YVMDETLGTATFTVSS 111
Cdd:cd08688    19 DLTDAFVEVkfgsTTYKTDVVKK-------SLNPVWNsEWFRFEVDDEelQDEPLQIRVMDHDtYSANDAIGKVYIDLNP 91


                  .
gi 1677530579 112 M 112
Cdd:cd08688    92 L 92
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 37-106 8.13e-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: 36.93  E-value: 8.13e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1677530579  37 DMLDTPDPYVELFISTtpDSRKRTRHFNNDINPVWNETFEF-ILDPNQENVLEITL--MDA-NYVMDETLGTAT 106
Cdd:cd04049    17 DFLGKIDPYVIIQCRT--QERKSKVAKGDGRNPEWNEKFKFtVEYPGWGGDTKLILriMDKdNFSDDDFIGEAT 88
 
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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