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Conserved domains on  [gi|310703680|ref|NP_001185517|]
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JMJD7-PLA2G4B protein isoform b [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Patatin_and_cPLA2 super family cl11396
Patatins and Phospholipases; Patatin-like phospholipase. This family consists of various ...
 474-880 0e+00

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


The actual alignment was detected with superfamily member cd07201:

Pssm-ID: 416256 [Multi-domain]  Cd Length: 541  Bit Score: 741.85  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 474 LKKEAGLRELAVRLGFGPCAEEQAFLSRRKQVVAAALRQALQLDGDLQEDEIPVVAIMATGGGIRAMTSLYGQLAGLKEL 553
Cdd:cd07201    1 LKAEESSEDLDVRLGFDLCAEEQEFLQKRKKVVAAALKKALQLEEDLQEDEVPVVAVMTTGGGTRALTSMYGSLLGLQKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 554 GLLDCVSYITGASGSTWALANLYEDPEWSQKDLAGPTELLKTQVTKNKLGVLAPSQLQRYRQELAERARLGYPSCFTNLW 633
Cdd:cd07201   81 GLLDCVSYITGLSGSTWTMATLYEDPNWSQKDLEGPIEEARKHVTKSKLGCFSPERLKYYRQELSEREQEGHKVSFIDLW 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 634 ALINEALLHDEPHDHKLSDQREALSHGQNPLPIYCALNTKGqSLTTFEFGEWCEFSPYEVGFPKYGAFIPSELFGSEFFM 713
Cdd:cd07201  161 GLIIESMLHDKKNDHKLSDQREAVSQGQNPLPIYLSLNVKD-NLSTQDFREWVEFTPYEVGFLKYGAFIPAEDFGSEFFM 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 714 GQLMKRLPESRICFLEGIWSNLYAANLQDSLYWASEPSQFWDRWVRNQANLDKEQVPLLKIEEPPST-----AGRIAEFF 788
Cdd:cd07201  240 GRLMKKLPESRICFLQGMWSSIFSLNLLDAWYLATGSEDFWHRWTRDKVNDIEDEPPLPPRPPERLTtlltpGGPLSQAF 319

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 789 TDLLTWRPLAQATHNFLRGLHFHKDYFQHPHFSTWKATTLDGLPNQLTPSEPHLCLLDVGYLINTSCLPLLQPTRDVDLI 868
Cdd:cd07201  320 RDFLTSRPTVSQYFNFLRGLQLHNDYLENKGFSTWKDTHLDAFPNQLTPSEDHLCLVDTAFFINTSYPPLLRPERKVDVI 399

                        410
                 ....*....|..
gi 310703680 869 LSLDYNLHGAFQ 880
Cdd:cd07201  400 LSLNYSLGSQFE 411
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 242-361 4.41e-57

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


:

Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 191.71  E-value: 4.41e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 242 LLTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVtGDD 321
Cdd:cd04036    1 LLTVRVLRATNITKGDLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV-MDD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 310703680 322 PVLSVLFDAGTLRAGEFRRESFSLSPQGEGRLEVEFRLQS 361
Cdd:cd04036   80 HLGTVLFDVSKLKLGEKVRVTFSLNPQGKEELEVEFLLEL 119
Cupin_8 pfam13621
Cupin-like domain; This cupin like domain shares similarity to the JmjC domain.
 38-223 1.33e-51

Cupin-like domain; This cupin like domain shares similarity to the JmjC domain.


:

Pssm-ID: 463936  Cd Length: 251  Bit Score: 181.41  E-value: 1.33e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   38 PLHFYRDWVCPNRPCIIRNALQHWPALQKWSLPYFRATVGST----EVSVAVTPDGYADAVRGD---RFMMPAERRLPLS 110
Cdd:pfam13621   1 PAEFFREYVAKNKPVVIRGAVKDWPAVQKWTDSSLLDYLKDKygdvEVTVEVTPDGRADRLFYNddfTFVNPKEERMPFG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  111 FVLDVLEGRAQHPGVLYVQKQCSNLPSELPQLLPDleSHVPWASEALGKMPDAVNFWLGEAAAVTSLHKDHYENLYCVVS 190
Cdd:pfam13621  81 EFLDRLEAGEDTDTAPYAYLQSDNLRSEFPELLED--NDLPFATEAFGGEPDAVNLWMGNGRSVTSLHYDHYENLYCVVR 158

                         170       180       190
                  ....*....|....*....|....*....|...
gi 310703680  191 GEKHFLFHPPSDRPFipyeLYtPATYQLTEEGT 223
Cdd:pfam13621 159 GRKRFTLFPPSDVPN----LY-PGPLEPTPEGQ 186
cPLA2_C2 pfam18695
Cytosolic phospholipases A2 C2-domain; Cytosolic phospholipases A2 (cPLA2s) consist of a ...
 382-473 2.62e-29

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


:

Pssm-ID: 465834  Cd Length: 111  Bit Score: 112.73  E-value: 2.62e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  382 CLHVQLEETGDQKSSEHR-VQLVVPGSCEGPQEASVG-----TGTFRFHCPACWEQELSIRLQ-----------DAPEEQ 444
Cdd:pfam18695   1 CLEVQVDSRGSKKEQGKKdLQLTVPGSYEGTQTISLGpepgcPDPFCFHYPKYWEPELHVELPkssvlqsgwnsDLEKET 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 310703680  445 --LKAPLSALPSGQVVRLVFPTSQEPLMRVE 473
Cdd:pfam18695  81 skLTVPLKSLPLGQEVTVPLPEGQELHLRLK 111
 
Name Accession Description Interval E-value
cPLA2_Grp-IVB-IVD-IVE-IVF cd07201
Group IVB, IVD, IVE, and IVF cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group ...
 474-880 0e+00

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: 741.85  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 474 LKKEAGLRELAVRLGFGPCAEEQAFLSRRKQVVAAALRQALQLDGDLQEDEIPVVAIMATGGGIRAMTSLYGQLAGLKEL 553
Cdd:cd07201    1 LKAEESSEDLDVRLGFDLCAEEQEFLQKRKKVVAAALKKALQLEEDLQEDEVPVVAVMTTGGGTRALTSMYGSLLGLQKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 554 GLLDCVSYITGASGSTWALANLYEDPEWSQKDLAGPTELLKTQVTKNKLGVLAPSQLQRYRQELAERARLGYPSCFTNLW 633
Cdd:cd07201   81 GLLDCVSYITGLSGSTWTMATLYEDPNWSQKDLEGPIEEARKHVTKSKLGCFSPERLKYYRQELSEREQEGHKVSFIDLW 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 634 ALINEALLHDEPHDHKLSDQREALSHGQNPLPIYCALNTKGqSLTTFEFGEWCEFSPYEVGFPKYGAFIPSELFGSEFFM 713
Cdd:cd07201  161 GLIIESMLHDKKNDHKLSDQREAVSQGQNPLPIYLSLNVKD-NLSTQDFREWVEFTPYEVGFLKYGAFIPAEDFGSEFFM 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 714 GQLMKRLPESRICFLEGIWSNLYAANLQDSLYWASEPSQFWDRWVRNQANLDKEQVPLLKIEEPPST-----AGRIAEFF 788
Cdd:cd07201  240 GRLMKKLPESRICFLQGMWSSIFSLNLLDAWYLATGSEDFWHRWTRDKVNDIEDEPPLPPRPPERLTtlltpGGPLSQAF 319

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 789 TDLLTWRPLAQATHNFLRGLHFHKDYFQHPHFSTWKATTLDGLPNQLTPSEPHLCLLDVGYLINTSCLPLLQPTRDVDLI 868
Cdd:cd07201  320 RDFLTSRPTVSQYFNFLRGLQLHNDYLENKGFSTWKDTHLDAFPNQLTPSEDHLCLVDTAFFINTSYPPLLRPERKVDVI 399

                        410
                 ....*....|..
gi 310703680 869 LSLDYNLHGAFQ 880
Cdd:cd07201  400 LSLNYSLGSQFE 411
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 242-361 4.41e-57

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


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 191.71  E-value: 4.41e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 242 LLTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVtGDD 321
Cdd:cd04036    1 LLTVRVLRATNITKGDLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV-MDD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 310703680 322 PVLSVLFDAGTLRAGEFRRESFSLSPQGEGRLEVEFRLQS 361
Cdd:cd04036   80 HLGTVLFDVSKLKLGEKVRVTFSLNPQGKEELEVEFLLEL 119
Cupin_8 pfam13621
Cupin-like domain; This cupin like domain shares similarity to the JmjC domain.
 38-223 1.33e-51

Cupin-like domain; This cupin like domain shares similarity to the JmjC domain.


Pssm-ID: 463936  Cd Length: 251  Bit Score: 181.41  E-value: 1.33e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   38 PLHFYRDWVCPNRPCIIRNALQHWPALQKWSLPYFRATVGST----EVSVAVTPDGYADAVRGD---RFMMPAERRLPLS 110
Cdd:pfam13621   1 PAEFFREYVAKNKPVVIRGAVKDWPAVQKWTDSSLLDYLKDKygdvEVTVEVTPDGRADRLFYNddfTFVNPKEERMPFG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  111 FVLDVLEGRAQHPGVLYVQKQCSNLPSELPQLLPDleSHVPWASEALGKMPDAVNFWLGEAAAVTSLHKDHYENLYCVVS 190
Cdd:pfam13621  81 EFLDRLEAGEDTDTAPYAYLQSDNLRSEFPELLED--NDLPFATEAFGGEPDAVNLWMGNGRSVTSLHYDHYENLYCVVR 158

                         170       180       190
                  ....*....|....*....|....*....|...
gi 310703680  191 GEKHFLFHPPSDRPFipyeLYtPATYQLTEEGT 223
Cdd:pfam13621 159 GRKRFTLFPPSDVPN----LY-PGPLEPTPEGQ 186
PLAc smart00022
Cytoplasmic phospholipase A2, catalytic subunit; Cytosolic phospholipases A2 hydrolyse ...
 485-732 6.04e-35

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


Pssm-ID: 214474  Cd Length: 549  Bit Score: 141.03  E-value: 6.04e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   485 VRLGFGPCAEEQAFLSRRKQVVAAALRQALQ------LDGDLQED-EIPVVAIMATGGGIRAMTSLYGQLAGLKEL---- 553
Cdd:smart00022  28 VRFSMGLSDNETEFLQKRKDYTNEAMKSFLGransnfLDSSLLNSsDVPKIAIAGSGGGFRAMVGGAGVLKAMDNRtdgh 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   554 ---GLLDCVSYITGASGSTWALANLYEDPEWSQKDLAGPTELLKTQVTKNKLG---VLAPSQLQRYRQELAERARLGYPS 627
Cdd:smart00022 108 glgGLLQSATYLAGLSGGTWLVGTLASNNFTPVKGPEEINSEWMFSVSINNPGinlLLTAQFYKSIVDAVWKKKDAGFNI 187

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   628 CFTNLWA-LINEALLHDEP-HDHKLSDQREA--LSHGQNPLPIYCAL----NTKGQSLTTFEFgewcEFSPYEVG--FPK 697
Cdd:smart00022 188 SLTDIWGrALSYNLFDSLGgPNYTLSSLRDQekFQNAEMPLPIFVADgrkpGESVINFNDTVF----EFSPFEFGswDPK 263

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 310703680   698 YGAFIPSELFGSEFFMGQLMKRLPESRICFLEGIW 732
Cdd:smart00022 264 LNAFMPPEYLGSKFFNGTPVKKGKCIPNFDNAGFI 298
cPLA2_C2 pfam18695
Cytosolic phospholipases A2 C2-domain; Cytosolic phospholipases A2 (cPLA2s) consist of a ...
 382-473 2.62e-29

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


Pssm-ID: 465834  Cd Length: 111  Bit Score: 112.73  E-value: 2.62e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  382 CLHVQLEETGDQKSSEHR-VQLVVPGSCEGPQEASVG-----TGTFRFHCPACWEQELSIRLQ-----------DAPEEQ 444
Cdd:pfam18695   1 CLEVQVDSRGSKKEQGKKdLQLTVPGSYEGTQTISLGpepgcPDPFCFHYPKYWEPELHVELPkssvlqsgwnsDLEKET 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 310703680  445 --LKAPLSALPSGQVVRLVFPTSQEPLMRVE 473
Cdd:pfam18695  81 skLTVPLKSLPLGQEVTVPLPEGQELHLRLK 111
PLA2_B pfam01735
Lysophospholipase catalytic domain; This family consists of Lysophospholipase / phospholipase ...
 528-872 4.06e-29

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: 122.48  E-value: 4.06e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  528 VAIMATGGGIRAMTSLYGQLAGL--------KELGLLDCVSYITGASGSTW-----ALANLYEDPEWSQKDLAGPTELLk 594
Cdd:pfam01735   1 IGIAGSGGGYRAMLGGAGVLAALdnrtdnetGLGGLLQSATYLAGLSGGSWlvgslAVNNFTSVQDFPDKPEDISIWDL- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  595 TQVTKNKLGVLAPSQLQRYR---QELAERARLGYPSCFTNLWA-LINEALLH--DEPHDHKLSDQREA--LSHGQNPLPI 666
Cdd:pfam01735  80 NHSIFNPGGLNIPQNIKRYDdivDAVWKKKNAGFNVSLTDIWGrALSYTLIPslRGGPNYTWSSLRDAewFQNAEMPFPI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  667 YCALNTK-GQSLTTFEfGEWCEFSPYEVGF--PKYGAFIPSELFGSEFFMGQLMKRLPESRICFLEGIW----SNLYaan 739
Cdd:pfam01735 160 IVADGRKpGTTVINLN-ATVFEFSPYEFGSwdPTLNSFTPTEYLGTKFFNGTPVKKGKCVPGFDNAGFVmgtsSTLF--- 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  740 lqdslywasepsqfwdrwvrNQAnldkeqvpLLKIeeppSTAGRIAEFFTDLLtwrplaqatHNFLRGL-HFHKDYFQHP 818
Cdd:pfam01735 236 --------------------NQF--------LLVI----NSTSSLPSFLNIII---------KHILKDLsEDSDDISQYP 274

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 310703680  819 HFSTWKATTLDGLPNQLTPSEPHLCLLDVGY-LINTSCLPLLQPTRDVDLILSLD 872
Cdd:pfam01735 275 PNPFQDANDINQNATNSIVDSDTLFLVDGGEdGQNIPLWPLLQPERDVDVIFAVD 329
C2 pfam00168
C2 domain;
241-345 5.73e-24

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 97.00  E-value: 5.73e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  241 CLLTVRVLQAHRLPSKDLVTPSDCYVTLWLpTACSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVTGD 320
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYL-LDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*
gi 310703680  321 DPVLSVLFDAGTLRAGEFRRESFSL 345
Cdd:pfam00168  80 DFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 242-339 1.64e-22

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 92.94  E-value: 1.64e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   242 LLTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVTGDD 321
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                           90
                   ....*....|....*...
gi 310703680   322 PVLSVLFDAGTLRAGEFR 339
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRH 98
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
243-324 2.90e-04

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 44.75  E-value: 2.90e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRlqTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDlVTGDDP 322
Cdd:COG5038  1042 LTIMLRSGENLPSSDENGYSDPFVKLFLNEKSVYK--TKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWD-SGEKND 1118


                  ..
gi 310703680  323 VL 324
Cdd:COG5038  1119 LL 1120
JmjC smart00558
A domain family that is part of the cupin metalloenzyme superfamily; Probable enzymes, but of ...
 132-191 3.15e-04

A domain family that is part of the cupin metalloenzyme superfamily; Probable enzymes, but of unknown functions, that regulate chromatin reorganisation processes (Clissold and Ponting, in press).


Pssm-ID: 214721  Cd Length: 58  Bit Score: 39.54  E-value: 3.15e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 310703680   132 CSNLPSELPQ---LLPDLESHVPWasealgkMPDAVNFWLGEAAAVTSLHKDHYE--NLYCVVSG 191
Cdd:smart00558   1 QLWNLAKLPFklnLLSDLPEDIPG-------PDVGPYLYMGMAGSTTPWHIDDYDlvNYLHQGAG 58
 
Name Accession Description Interval E-value
cPLA2_Grp-IVB-IVD-IVE-IVF cd07201
Group IVB, IVD, IVE, and IVF cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group ...
 474-880 0e+00

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: 741.85  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 474 LKKEAGLRELAVRLGFGPCAEEQAFLSRRKQVVAAALRQALQLDGDLQEDEIPVVAIMATGGGIRAMTSLYGQLAGLKEL 553
Cdd:cd07201    1 LKAEESSEDLDVRLGFDLCAEEQEFLQKRKKVVAAALKKALQLEEDLQEDEVPVVAVMTTGGGTRALTSMYGSLLGLQKL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 554 GLLDCVSYITGASGSTWALANLYEDPEWSQKDLAGPTELLKTQVTKNKLGVLAPSQLQRYRQELAERARLGYPSCFTNLW 633
Cdd:cd07201   81 GLLDCVSYITGLSGSTWTMATLYEDPNWSQKDLEGPIEEARKHVTKSKLGCFSPERLKYYRQELSEREQEGHKVSFIDLW 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 634 ALINEALLHDEPHDHKLSDQREALSHGQNPLPIYCALNTKGqSLTTFEFGEWCEFSPYEVGFPKYGAFIPSELFGSEFFM 713
Cdd:cd07201  161 GLIIESMLHDKKNDHKLSDQREAVSQGQNPLPIYLSLNVKD-NLSTQDFREWVEFTPYEVGFLKYGAFIPAEDFGSEFFM 239

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 714 GQLMKRLPESRICFLEGIWSNLYAANLQDSLYWASEPSQFWDRWVRNQANLDKEQVPLLKIEEPPST-----AGRIAEFF 788
Cdd:cd07201  240 GRLMKKLPESRICFLQGMWSSIFSLNLLDAWYLATGSEDFWHRWTRDKVNDIEDEPPLPPRPPERLTtlltpGGPLSQAF 319

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 789 TDLLTWRPLAQATHNFLRGLHFHKDYFQHPHFSTWKATTLDGLPNQLTPSEPHLCLLDVGYLINTSCLPLLQPTRDVDLI 868
Cdd:cd07201  320 RDFLTSRPTVSQYFNFLRGLQLHNDYLENKGFSTWKDTHLDAFPNQLTPSEDHLCLVDTAFFINTSYPPLLRPERKVDVI 399

                        410
                 ....*....|..
gi 310703680 869 LSLDYNLHGAFQ 880
Cdd:cd07201  400 LSLNYSLGSQFE 411
cPLA2_like cd00147
Cytosolic phospholipase A2, catalytic domain; hydrolyses arachidonyl phospholipids; Catalytic ...
 485-873 1.91e-152

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: 455.55  E-value: 1.91e-152
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 485 VRLGFGPCAEEQAFLSRRKQVVAAALRQALQLDGDLQEDEIPVVAIMATGGGIRAMTSLYGQLAGLKELGLLDCVSYITG 564
Cdd:cd00147    1 VRLASDLCDEEKEFLEKRRKVVAKALKKFLGLENDLNPDEVPVIAILGSGGGYRAMTGGAGALKALDEGGLLDCVTYLSG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 565 ASGSTWALANLYEDPEWSQKDLAGPTELLKTQVTKNKLGVLAPSQLQRYRQELAERARLGYPSCFTNLWALINEALLHDE 644
Cdd:cd00147   81 LSGSTWLMASLYSNPDWSQKDLDEAIEWLKRHVIKSPLLLFSPERLKYYAKELEEKKKAGFNVSLTDFWGLLLGYTLLKE 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 645 PHDHKLSDQREALSHGQNPLPIYCALNTKGQSLTTFEFGEWCEFSPYEVGFPKYGAFIPSELFGSEFFMGQLMKRLPESR 724
Cdd:cd00147  161 LTDSSLSDQREFVQNGQNPLPIYTALNVKPGETSINDFATWFEFTPYEVGFPKYGAFIPTEYFGSKFFMGRLVKKIPEDR 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 725 ICFLEGIWSNLYAANLQDslywasepsqfwdrwvrnqanldkeqvpllkieeppstagriaefftdlltwrplAQATHNF 804
Cdd:cd00147  241 LGFLMGTWGSAFSIILLD-------------------------------------------------------AGKYPNF 265

                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 805 LRGLHFHKDYFqhphfstwkattldGLPNQLTPSEPHLCLLDVGYLINTSCL-PLLQPTRDVDLILSLDY 873
Cdd:cd00147  266 FYGLNLHKSYL--------------RSPNPLITSSDTLHLVDAGLDINNIPLpPLLRPERDVDVILSFDF 321
cPLA2_Grp-IVA cd07200
Group IVA cytosolic phospholipase A2; catalytic domain; Ca-dependent; Group IVA cPLA2, an 85 ...
 486-873 1.06e-62

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: 220.40  E-value: 1.06e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 486 RLGFGPCAEEQAFLSRRKQVVAAALRQALQLDGDLQE--DEIPVVAIMATGGGIRAMTSLYGQLAGLKELGLLDCVSYIT 563
Cdd:cd07200    2 RFSMALCDEEKEFRQARKMRVREALRKLLGEEGPKVTslREVPVIALLGSGGGFRAMVGMSGAMKALYDSGVLDCATYVA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 564 GASGSTWALANLYEDPEWSQKdlaGPTEL---LKTQVTKNKLGVLAPSQLQRYRQELAERARLGYPSCFTNLWA-LINEA 639
Cdd:cd07200   82 GLSGSTWYMSTLYSHPDFPEK---GPGEInkeLMRNVSSSPLLLLTPQLLKRYTEALWEKKSSGQPVTFTDFFGmLIGET 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 640 LLHDEpHDHKLSDQREALSHGQNPLPIYCALNTKGQSLTTfEFGEWCEFSPYEVGFPKYGAFIPSELFGSEFFMGQLMKR 719
Cdd:cd07200  159 LIKER-MDTKLSDLQEKVNDGQVPLPLFTCLHVKPDVSAL-MFHDWVEFSPYEIGMAKYGTFMSPDLFGSKFFMGFLAKK 236

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 720 LPESRICFLEGIWSNLYaanlqdslywasepSQFWDRWV-RNqanldkeqvpllkieeppSTAGRIAEFftdlltwrpla 798
Cdd:cd07200  237 YPENPLHFLMGVWGSAF--------------SILFNRVLgRN------------------SREGRAGKV----------- 273

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 799 qatHNFLRGLHFHKDYFqhphFSTWKATTLDGLPNQLT-------PSEP--------HLCllDVGYLINtSCLPLLQ-PT 862
Cdd:cd07200  274 ---HNFMLGLNLNTSYP----LSPLSDLATDEPEAAVAdadeferIYEPldtkskkiHVV--DSGLTFN-LPYPLILrPQ 343

                        410
                 ....*....|.
gi 310703680 863 RDVDLILSLDY 873
Cdd:cd07200  344 RGVDLIISFDF 354
C2_cPLA2 cd04036
C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...
 242-361 4.41e-57

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


Pssm-ID: 176001 [Multi-domain]  Cd Length: 119  Bit Score: 191.71  E-value: 4.41e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 242 LLTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVtGDD 321
Cdd:cd04036    1 LLTVRVLRATNITKGDLLSTPDCYVELWLPTASDEKKRTKTIKNSINPVWNETFEFRIQSQVKNVLELTVMDEDYV-MDD 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 310703680 322 PVLSVLFDAGTLRAGEFRRESFSLSPQGEGRLEVEFRLQS 361
Cdd:cd04036   80 HLGTVLFDVSKLKLGEKVRVTFSLNPQGKEELEVEFLLEL 119
cPLA2_Grp-IVC cd07202
Group IVC cytoplasmic phospholipase A2; catalytic domain; Ca-independent; Group IVC cPLA2, a ...
 494-873 1.79e-53

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: 192.31  E-value: 1.79e-53
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 494 EEQAFLSRRKQVVAAALRQAlqldgDLQEDEIPVVAIMATGGGIRAMTSLYGQLAGLKELGLLDCVSYITGASGSTWALA 573
Cdd:cd07202   12 EEKAAVVKRRKDVLQSLQKL-----GINADKAPVIAVLGSGGGLRAMIACLGVLSELDKAGLLDCVTYLAGVSGSTWCMS 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 574 NLYEDPEWSQKdLAGPTELLKTQVTKNKLGVLApsQLQRYRQElaerARLGYPScFTNLWALINEALLHDEPHDHKLSDQ 653
Cdd:cd07202   87 SLYTEPDWSTK-LQTVEDELKRRLQKVSWDFAY--ALKKEIQA----AKSDNFS-LTDFWAYLVVTTFTKELDESTLSDQ 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 654 REALSHGQNPLPIYCALNTKGQSLTTFEFGE-WCEFSPYEVGFPKYGAFIPSELFGSEFFMGQLMKRLPESRICFLEGIW 732
Cdd:cd07202  159 RKQSEEGKDPYPIFAAIDKDLSEWKERKTGDpWFEFTPHEAGYPLPGAFVSTTHFGSKFENGKLVKQEPERDLLYLRALW 238

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 733 SNLYAanlqdslywasepsqfwdrwvrnqanlDKEQvpllkieeppstagrIAEFFT-DLLTWrplaQATHNFlrgLHFH 811
Cdd:cd07202  239 GSALA---------------------------DGEE---------------IAKYICmSLWIW----GTTYNF---LYKH 269

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 310703680 812 KDYFQHPHFstwkattldglpnqltPSEPHLCLLDVGYLINTSCLPLLQPTRDVDLILSLDY 873
Cdd:cd07202  270 GDIADKPAM----------------RSRETLHLMDAGLAINSPYPLVLPPVRNTDLILSFDF 315
Cupin_8 pfam13621
Cupin-like domain; This cupin like domain shares similarity to the JmjC domain.
 38-223 1.33e-51

Cupin-like domain; This cupin like domain shares similarity to the JmjC domain.


Pssm-ID: 463936  Cd Length: 251  Bit Score: 181.41  E-value: 1.33e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   38 PLHFYRDWVCPNRPCIIRNALQHWPALQKWSLPYFRATVGST----EVSVAVTPDGYADAVRGD---RFMMPAERRLPLS 110
Cdd:pfam13621   1 PAEFFREYVAKNKPVVIRGAVKDWPAVQKWTDSSLLDYLKDKygdvEVTVEVTPDGRADRLFYNddfTFVNPKEERMPFG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  111 FVLDVLEGRAQHPGVLYVQKQCSNLPSELPQLLPDleSHVPWASEALGKMPDAVNFWLGEAAAVTSLHKDHYENLYCVVS 190
Cdd:pfam13621  81 EFLDRLEAGEDTDTAPYAYLQSDNLRSEFPELLED--NDLPFATEAFGGEPDAVNLWMGNGRSVTSLHYDHYENLYCVVR 158

                         170       180       190
                  ....*....|....*....|....*....|...
gi 310703680  191 GEKHFLFHPPSDRPFipyeLYtPATYQLTEEGT 223
Cdd:pfam13621 159 GRKRFTLFPPSDVPN----LY-PGPLEPTPEGQ 186
PLAc smart00022
Cytoplasmic phospholipase A2, catalytic subunit; Cytosolic phospholipases A2 hydrolyse ...
 485-732 6.04e-35

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


Pssm-ID: 214474  Cd Length: 549  Bit Score: 141.03  E-value: 6.04e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   485 VRLGFGPCAEEQAFLSRRKQVVAAALRQALQ------LDGDLQED-EIPVVAIMATGGGIRAMTSLYGQLAGLKEL---- 553
Cdd:smart00022  28 VRFSMGLSDNETEFLQKRKDYTNEAMKSFLGransnfLDSSLLNSsDVPKIAIAGSGGGFRAMVGGAGVLKAMDNRtdgh 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   554 ---GLLDCVSYITGASGSTWALANLYEDPEWSQKDLAGPTELLKTQVTKNKLG---VLAPSQLQRYRQELAERARLGYPS 627
Cdd:smart00022 108 glgGLLQSATYLAGLSGGTWLVGTLASNNFTPVKGPEEINSEWMFSVSINNPGinlLLTAQFYKSIVDAVWKKKDAGFNI 187

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   628 CFTNLWA-LINEALLHDEP-HDHKLSDQREA--LSHGQNPLPIYCAL----NTKGQSLTTFEFgewcEFSPYEVG--FPK 697
Cdd:smart00022 188 SLTDIWGrALSYNLFDSLGgPNYTLSSLRDQekFQNAEMPLPIFVADgrkpGESVINFNDTVF----EFSPFEFGswDPK 263

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 310703680   698 YGAFIPSELFGSEFFMGQLMKRLPESRICFLEGIW 732
Cdd:smart00022 264 LNAFMPPEYLGSKFFNGTPVKKGKCIPNFDNAGFI 298
cPLA2_C2 pfam18695
Cytosolic phospholipases A2 C2-domain; Cytosolic phospholipases A2 (cPLA2s) consist of a ...
 382-473 2.62e-29

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


Pssm-ID: 465834  Cd Length: 111  Bit Score: 112.73  E-value: 2.62e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  382 CLHVQLEETGDQKSSEHR-VQLVVPGSCEGPQEASVG-----TGTFRFHCPACWEQELSIRLQ-----------DAPEEQ 444
Cdd:pfam18695   1 CLEVQVDSRGSKKEQGKKdLQLTVPGSYEGTQTISLGpepgcPDPFCFHYPKYWEPELHVELPkssvlqsgwnsDLEKET 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 310703680  445 --LKAPLSALPSGQVVRLVFPTSQEPLMRVE 473
Cdd:pfam18695  81 skLTVPLKSLPLGQEVTVPLPEGQELHLRLK 111
PLA2_B pfam01735
Lysophospholipase catalytic domain; This family consists of Lysophospholipase / phospholipase ...
 528-872 4.06e-29

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: 122.48  E-value: 4.06e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  528 VAIMATGGGIRAMTSLYGQLAGL--------KELGLLDCVSYITGASGSTW-----ALANLYEDPEWSQKDLAGPTELLk 594
Cdd:pfam01735   1 IGIAGSGGGYRAMLGGAGVLAALdnrtdnetGLGGLLQSATYLAGLSGGSWlvgslAVNNFTSVQDFPDKPEDISIWDL- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  595 TQVTKNKLGVLAPSQLQRYR---QELAERARLGYPSCFTNLWA-LINEALLH--DEPHDHKLSDQREA--LSHGQNPLPI 666
Cdd:pfam01735  80 NHSIFNPGGLNIPQNIKRYDdivDAVWKKKNAGFNVSLTDIWGrALSYTLIPslRGGPNYTWSSLRDAewFQNAEMPFPI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  667 YCALNTK-GQSLTTFEfGEWCEFSPYEVGF--PKYGAFIPSELFGSEFFMGQLMKRLPESRICFLEGIW----SNLYaan 739
Cdd:pfam01735 160 IVADGRKpGTTVINLN-ATVFEFSPYEFGSwdPTLNSFTPTEYLGTKFFNGTPVKKGKCVPGFDNAGFVmgtsSTLF--- 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  740 lqdslywasepsqfwdrwvrNQAnldkeqvpLLKIeeppSTAGRIAEFFTDLLtwrplaqatHNFLRGL-HFHKDYFQHP 818
Cdd:pfam01735 236 --------------------NQF--------LLVI----NSTSSLPSFLNIII---------KHILKDLsEDSDDISQYP 274

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 310703680  819 HFSTWKATTLDGLPNQLTPSEPHLCLLDVGY-LINTSCLPLLQPTRDVDLILSLD 872
Cdd:pfam01735 275 PNPFQDANDINQNATNSIVDSDTLFLVDGGEdGQNIPLWPLLQPERDVDVIFAVD 329
C2 pfam00168
C2 domain;
241-345 5.73e-24

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 97.00  E-value: 5.73e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  241 CLLTVRVLQAHRLPSKDLVTPSDCYVTLWLpTACSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVTGD 320
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYL-LDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*
gi 310703680  321 DPVLSVLFDAGTLRAGEFRRESFSL 345
Cdd:pfam00168  80 DFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 242-339 1.64e-22

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 92.94  E-value: 1.64e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680   242 LLTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVTGDD 321
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                           90
                   ....*....|....*...
gi 310703680   322 PVLSVLFDAGTLRAGEFR 339
Cdd:smart00239  81 FIGQVTIPLSDLLLGGRH 98
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 243-345 3.63e-20

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 86.35  E-value: 3.63e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRlqTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVTGDDP 322
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKFK--TKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDF 78

                         90       100
                 ....*....|....*....|....
gi 310703680 323 VLSVLFDAGTLRA-GEFRRESFSL 345
Cdd:cd00030   79 LGEVEIPLSELLDsGKEGELWLPL 102
cPLA2_Fungal_PLB cd07203
Fungal Phospholipase B-like; cPLA2 GrpIVA homologs; catalytic domain; Fungal phospholipase B ...
 494-872 3.91e-17

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: 85.88  E-value: 3.91e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 494 EEQAFLSRRKQVVAAALRQALQ---LDGDLQED-----EIPVVAIMATGGGIRAMTSLYGQLAGL---------KEL-GL 555
Cdd:cd07203   23 NEQEYLEKRRSITNSALKDFLSranLNGDDDLDsnnssNGPRIGIAVSGGGYRAMLTGAGAIAAMdnrtdnateHGLgGL 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 556 LDCVSYITGASGSTWALANLYEDpewsqkDLAGPTELLKTQVTKNKLGVLAPS------QLQRY---RQELAERARLGYP 626
Cdd:cd07203  103 LQSSTYLSGLSGGSWLVGSLASN------NFTSVQDLLADSIWNLDHSIFNPYgaaivkTLNYYtnlANEVAQKKDAGFN 176

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 627 SCFTNLWALINEALLHDEPH---DHKLSDQR--EALSHGQNPLPIYCALN----TKGQSLTTFEFgewcEFSPYEVGF-- 695
Cdd:cd07203  177 VSLTDIWGRALSYQLFPALRggpNLTWSSIRnqSWFQNAEMPFPIIVADGrypgETIINLNATVF----EFTPYEFGSwd 252

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 696 PKYGAFIPSELFGSEFFMGQlmkrlPESRIC--------FLEGIWSNLYaanlqdslywasepsqfwdrwvrNQAnldke 767
Cdd:cd07203  253 PSLNSFTPTEYLGTNVSNGV-----PPNGSCvngfdnagFVMGTSSTLF-----------------------NQF----- 299

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 768 qvpLLKIeeppsTAGRIAEFFTDLltwrplaqATHNFLRGLHFHKD---YFQHPhFSTWKATTLDGLpNQLTPSePHLCL 844
Cdd:cd07203  300 ---LLQI-----NSTSSPSFIKLI--------ATGFLLDILKENQDiasYIPNP-FQGYTYSNSNGT-NPIVDS-DYLDL 360

                        410       420
                 ....*....|....*....|....*....
gi 310703680 845 LDVGY-LINTSCLPLLQPTRDVDLILSLD 872
Cdd:cd07203  361 VDGGEdGQNIPLWPLLQPERDVDVIFAFD 389
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 243-321 1.22e-12

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: 65.68  E-value: 1.22e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLpTACSHRL---QTRTVKNSSSPVWNQSFHFRI-HRQLKNV-MELKVFDQDLV 317
Cdd:cd00276   16 LTVVVLKARNLPPSDGKGLSDPYVKVSL-LQGGKKLkkkKTSVKKGTLNPVFNEAFSFDVpAEQLEEVsLVITVVDKDSV 94


                 ....
gi 310703680 318 TGDD 321
Cdd:cd00276   95 GRNE 98
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 243-332 1.67e-12

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: 64.96  E-value: 1.67e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACS--HRLQTRTVKNSSSPVWNQSF---HFRIHRQLKNVMELKVFDQDLV 317
Cdd:cd04031   18 LIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSekSKRRTKTVKKTLNPEWNQTFeysNVRRETLKERTLEVTVWDYDRD 97

                         90
                 ....*....|....*
gi 310703680 318 TGDDPVLSVLFDAGT 332
Cdd:cd04031   98 GENDFLGEVVIDLAD 112
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 242-359 3.14e-12

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: 64.68  E-value: 3.14e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 242 LLTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHR----LQTRTVKNSSSPVWNQSFHFRIHRQlKNVMELKVFDQDLV 317
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPDGNGeidsVQTKTIKKTLNPKWNEEFFFRVNPR-EHRLLFEVFDENRL 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 310703680 318 TGDD-------PVLSVLFDAGTlRAGEFRRESFSLSPQGE-GRLEVEFRL 359
Cdd:cd04033   80 TRDDflgqvevPLNNLPTETPG-NERRYTFKDYLLRPRSSkSRVKGHLRL 128
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 243-323 6.39e-11

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: 60.42  E-value: 6.39e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRLQTRTVKNSSSPVWNQSFHFR---IHRQLKNVMELKVFDQDLVTG 319
Cdd:cd08386   18 LTLKILKAVELPAKDFSGTSDPFVKIYLLPDKKHKLETKVKRKNLNPHWNETFLFEgfpYEKLQQRVLYLQVLDYDRFSR 97


                 ....
gi 310703680 320 DDPV 323
Cdd:cd08386   98 NDPI 101
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 243-322 9.73e-10

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: 56.81  E-value: 9.73e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTacSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVTGDDP 322
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLNG--EKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGGKDDL 78
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 242-315 1.67e-09

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


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 56.15  E-value: 1.67e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 310703680 242 LLTVRVLQAHRLPSKDLVTPSDCYVTLWLptaCSHRLQTRTVKNSSSPVWNQSFHFRIhRQLKNVMELKVFDQD 315
Cdd:cd08377    2 FLQVKVIRASGLAAADIGGKSDPFCVLEL---VNARLQTHTIYKTLNPEWNKIFTFPI-KDIHDVLEVTVYDED 71
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 242-322 1.79e-09

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: 56.95  E-value: 1.79e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 242 LLTVRVLQAHRLPSKDLVTpSDCYVTLWLPtacSHRLQTRTVKNSSSPVWNQSFHFRIhRQLKNVMELKVFDQDLVTGDD 321
Cdd:cd04038    3 LLKVRVVRGTNLAVRDFTS-SDPYVVLTLG---NQKVKTRVIKKNLNPVWNEELTLSV-PNPMAPLKLEVFDKDTFSKDD 77


                 .
gi 310703680 322 P 322
Cdd:cd04038   78 S 78
Patatin_and_cPLA2 cd01819
Patatins and Phospholipases; Patatin-like phospholipase. This family consists of various ...
 530-576 2.17e-09

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: 57.04  E-value: 2.17e-09
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 310703680 530 IMATGGGIRAMtSLYGQLAGLKELGLLDCVSYITGASGSTWALANLY 576
Cdd:cd01819    1 LSFSGGGFRGM-YHAGVLSALAERGLLDCVTYLAGTSGGAWVAATLY 46
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 242-315 5.00e-09

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


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 54.49  E-value: 5.00e-09
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 310703680 242 LLTVRVLQAHRLPSKDLVTPSDCYVTLwlpTACSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQD 315
Cdd:cd04050    1 LLFVYLDSAKNLPLAKSTKEPSPYVEL---TVGKTTQKSKVKERTNNPVWEEGFTFLVRNPENQELEIEVKDDK 71
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 242-356 3.57e-08

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: 52.65  E-value: 3.57e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 242 LLTVRVLQAHRLPSKDLVTPSDCYVTLwLPTACSHRL-QTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVtGD 320
Cdd:cd04043    2 LFTIRIVRAENLKADSSNGLSDPYVTL-VDTNGKRRIaKTRTIYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFV-GK 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 310703680 321 DPVL---SVLFDAGTLRAGEFRRE-SFSLSPQGEGRLEVE 356
Cdd:cd04043   80 HDLCgraSLKLDPKRFGDDGLPREiWLDLDTQGRLLLRVS 119
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 228-332 5.44e-08

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: 53.10  E-value: 5.44e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 228 DEEAMEKAEVSRTCLLTVRVLQAHRLPSKDLVTPSDCYV--TLWLPTACSHRLQTRTVKNSSSPVWNQSFHFR--IHRQL 303
Cdd:cd04020   14 ESEGALKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVkcYLLPDKSKKSKQKTPVVKKSVNPVWNHTFVYDgvSPEDL 93

                         90       100       110
                 ....*....|....*....|....*....|
gi 310703680 304 KNV-MELKVFDQDLVTGDDPVLSVLFDAGT 332
Cdd:cd04020   94 SQAcLELTVWDHDKLSSNDFLGGVRLGLGT 123
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 243-362 5.79e-08

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


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 52.10  E-value: 5.79e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPtacSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVTGDDP 322
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTSDPFVRVFYN---GQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKNDF 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 310703680 323 VLSVLFDAGTLRAGEFRRESFSLSPQGEGRLEVEFRLQSL 362
Cdd:cd04025   79 LGKVVFSIQTLQQAKQEEGWFRLLPDPRAEEESGGNLGSL 118
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 243-321 3.19e-07

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 50.34  E-value: 3.19e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWL-PTA-CSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKN---VMElkVFDQDLV 317
Cdd:cd04026   15 LTVEVREAKNLIPMDPNGLSDPYVKLKLiPDPkNETKQKTKTIKKTLNPVWNETFTFDLKPADKDrrlSIE--VWDWDRT 92


                 ....
gi 310703680 318 TGDD 321
Cdd:cd04026   93 TRND 96
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 240-323 3.05e-06

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: 47.15  E-value: 3.05e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 240 TCLLTVRVLQAHRLP--SKDLVTPSDCYVTLWL---PTACSHRLQTRTVK-NSSSPVWNQSFHFRIHrqlknVMEL---- 309
Cdd:cd00275    1 PLTLTIKIISGQQLPkpKGDKGSIVDPYVEVEIhglPADDSAKFKTKVVKnNGFNPVWNETFEFDVT-----VPELaflr 75

                         90
                 ....*....|....*
gi 310703680 310 -KVFDQDlVTGDDPV 323
Cdd:cd00275   76 fVVYDED-SGDDDFL 89
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 243-299 4.01e-06

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: 46.87  E-value: 4.01e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRLQTRTVKNSSSPVWNQSFHFRI 299
Cdd:cd08385   18 LTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKKKFETKVHRKTLNPVFNETFTFKV 74
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 241-315 4.37e-06

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: 46.79  E-value: 4.37e-06
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 310703680 241 CLLTVRVLQAHRLPSKDLVTPSDCYVTLWLPTAcshRLQTRTVKNSSSPVWNQSFHFRIHRQlKNVMELKVFDQD 315
Cdd:cd04027    1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGKT---KKRTKTIPQNLNPVWNEKFHFECHNS-SDRIKVRVWDED 71
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 243-357 5.74e-06

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


Pssm-ID: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 46.10  E-value: 5.74e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLvtpSDCYVTLWLPTACSHRLQTRTVKNsssPVWNQSFHFRIHRQLKNVMELK--VFDQDLVTGD 320
Cdd:cd08383    2 LRLRILEAKNLPSKGT---RDPYCTVSLDQVEVARTKTVEKLN---PFWGEEFVFDDPPPDVTFFTLSfyNKDKRSKDRD 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 310703680 321 DPVLSVLFDAGTLraGEFRRESFSLSP-------QGEGRLEVEF 357
Cdd:cd08383   76 IVIGKVALSKLDL--GQGKDEWFPLTPvdpdsevQGSVRLRARY 117
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 243-335 1.40e-05

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: 45.49  E-value: 1.40e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVT--PSDCYVTLwlpTACSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVTGD 320
Cdd:cd04024    3 LRVHVVEAKDLAAKDRSGkgKSDPYAIL---SVGAQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGK 79

                         90
                 ....*....|....*
gi 310703680 321 DPVLSVLFDAGTLRA 335
Cdd:cd04024   80 DYLGEFDIALEEVFA 94
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 242-334 1.40e-05

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


Pssm-ID: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 45.34  E-value: 1.40e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 242 LLTVRVLQAHRLPSKDLVTPSDCYVTLwlptacshRLQTRTVKNSSS------PVWNQSFHFRIhRQLKNVMELKVFDQD 315
Cdd:cd04042    1 QLDIHLKEGRNLAARDRGGTSDPYVKF--------KYGGKTVYKSKTiyknlnPVWDEKFTLPI-EDVTQPLYIKVFDYD 71

                         90
                 ....*....|....*....
gi 310703680 316 LVTGDDPVLSVLFDAGTLR 334
Cdd:cd04042   72 RGLTDDFMGSAFVDLSTLE 90
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 243-321 2.00e-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: 2.00e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTAcSHRLQ---TRTVKNSSSPVWNQSFHFRI--HRQLKNVMELKVFDQDLV 317
Cdd:cd08405   17 ITVNIIKARNLKAMDINGTSDPYVKVWLMYK-DKRVEkkkTVIKKRTLNPVFNESFIFNIplERLRETTLIITVMDKDRL 95


                 ....
gi 310703680 318 TGDD 321
Cdd:cd08405   96 SRND 99
C2_Perforin cd04032
C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and ...
 243-321 2.23e-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: 44.56  E-value: 2.23e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLpSKDLVTPSDCYVTLWLPtacSHRLQTRTVKNSSSPVWNQSFHF-----RIHRQLKnvmeLKVFDQDLV 317
Cdd:cd04032   30 LTVTVLRATGL-WGDYFTSTDGYVKVFFG---GQEKRTEVIWNNNNPRWNATFDFgsvelSPGGKLR----FEVWDRDNG 101


                 ....
gi 310703680 318 TGDD 321
Cdd:cd04032  102 WDDD 105
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 261-296 3.41e-05

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


Pssm-ID: 175982 [Multi-domain]  Cd Length: 158  Bit Score: 44.99  E-value: 3.41e-05
                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 310703680 261 PSDCYVTLWLPTAcshRL-QTRTVKNSSSPVWNQSFH 296
Cdd:cd04015   57 TSDPYATVDLAGA---RVaRTRVIENSENPVWNESFH 90
C2B_MCTP_PRT_plant cd08378
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 243-329 3.84e-05

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: 43.84  E-value: 3.84e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKdlvtPSDCYVTLWLPTacsHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVTgDDP 322
Cdd:cd08378    2 LYVRVVKARGLPAN----SNDPVVEVKLGN---YKGSTKAIERTSNPEWNQVFAFSKDRLQGSTLEVSVWDKDKAK-DDF 73


                 ....*..
gi 310703680 323 VLSVLFD 329
Cdd:cd08378   74 LGGVCFD 80
C2_fungal_Inn1p-like cd08681
C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...
 243-315 6.36e-05

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176063 [Multi-domain]  Cd Length: 118  Bit Score: 43.39  E-value: 6.36e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTAcshRLQTRTVKNS-SSPVWNQSFHFRIHRQLKNVMELKVFDQD 315
Cdd:cd08681    3 LVVVVLKARNLPNKRKLDKQDPYCVLRIGGV---TKKTKTDFRGgQHPEWDEELRFEITEDKKPILKVAVFDDD 73
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 242-315 6.92e-05

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


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 43.16  E-value: 6.92e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 310703680 242 LLTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRLQTRTVKNSSSPVWNQSFHFRIHRQL--KNVMELKVFDQD 315
Cdd:cd08387   17 ILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNTKQSKIHKKTLNPEFDESFVFEVPPQElpKRTLEVLLYDFD 92
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 278-355 8.31e-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: 42.59  E-value: 8.31e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 278 LQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLvtGDDPVLSV-------LFDAgTLRAGEFrresFSLSPQGE 350
Cdd:cd04052   27 YTTRVKKKTNNPSWNASTEFLVTDRRKSRVTVVVKDDRD--RHDPVLGSvsislndLIDA-TSVGQQW----FPLSGNGQ 99


                 ....*
gi 310703680 351 GRLEV 355
Cdd:cd04052  100 GRIRI 104
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 241-354 1.06e-04

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


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 42.66  E-value: 1.06e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 241 CLLTVRVLQAHRLPSKD-----LVTP-SDCYVTLWLPTacsHRLQTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQ 314
Cdd:cd08391    1 GVLRIHVIEAQDLVAKDkfvggLVKGkSDPYVIVRVGA---QTFKSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDE 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 310703680 315 DlVTGDDPVLSVLFDAGTLRAGEFRRESFSLSPQGEGRLE 354
Cdd:cd08391   78 D-PDKDDFLGRLSIDLGSVEKKGFIDEWLPLEDVKSGRLH 116
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 248-321 1.12e-04

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 42.56  E-value: 1.12e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 248 LQAHRLPSKDLVTPSDCYVTLWLPTACSHRL----QTRTVKNSSSPVWNQSF----HFRIHRQLKnvmeLKVFDQDLVTG 319
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVVYVKTGGSGQWveigRTEVIKNNLNPDFVTTFtvdyYFEEVQKLR----FEVYDVDSKSK 82


                 ..
gi 310703680 320 DD 321
Cdd:cd04048   83 DL 84
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 243-335 1.16e-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: 42.80  E-value: 1.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRLQTRT-VKNSS-SPVWNQSFHFRI-HRQLKNV-MELKVFDQDLVT 318
Cdd:cd08404   17 LTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRISKKKThVKKCTlNPVFNESFVFDIpSEELEDIsVEFLVLDSDRVT 96

                         90
                 ....*....|....*..
gi 310703680 319 gDDPVLSVLFDAGTLRA 335
Cdd:cd08404   97 -KNEVIGRLVLGPKASG 112
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 243-300 1.41e-04

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


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 42.32  E-value: 1.41e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPtacSHRLQTRTVKNSSSPVWNQSFHFRIH 300
Cdd:cd04022    2 LVVEVVDAQDLMPKDGQGSSSAYVELDFD---GQKKRTRTKPKDLNPVWNEKLVFNVS 56
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 243-333 2.42e-04

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: 41.52  E-value: 2.42e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPS-DCYVTLWLPtacSHRLQTRTVKNSSSPVWN-QSFHFRI-HRQLK-NVMELKVFDQDLVT 318
Cdd:cd08688    1 LKVRVVAARDLPVMDRSSDLtDAFVEVKFG---STTYKTDVVKKSLNPVWNsEWFRFEVdDEELQdEPLQIRVMDHDTYS 77

                         90
                 ....*....|....*
gi 310703680 319 GDDPVLSVLFDAGTL 333
Cdd:cd08688   78 ANDAIGKVYIDLNPL 92
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 242-342 2.71e-04

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: 41.09  E-value: 2.71e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 242 LLTVRVLQAHRLPSKDLVTP-SDCYVTLWLPTACSHRLQTRTVKNSSSPVWNQSfHF--------RIHRQLKnvmeLKVF 312
Cdd:cd04041    2 VLVVTIHRATDLPKADFGTGsSDPYVTASFAKFGKPLYSTRIIRKDLNPVWEET-WFvlvtpdevKAGERLS----CRLW 76

                         90       100       110
                 ....*....|....*....|....*....|...
gi 310703680 313 DQDLVTGDDPVLSVLFDAGTLRAGE---FRRES 342
Cdd:cd04041   77 DSDRFTADDRLGRVEIDLKELIEDRnwmGRRED 109
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
243-324 2.90e-04

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 44.75  E-value: 2.90e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680  243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRlqTRTVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDlVTGDDP 322
Cdd:COG5038  1042 LTIMLRSGENLPSSDENGYSDPFVKLFLNEKSVYK--TKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWD-SGEKND 1118


                  ..
gi 310703680  323 VL 324
Cdd:COG5038  1119 LL 1120
JmjC smart00558
A domain family that is part of the cupin metalloenzyme superfamily; Probable enzymes, but of ...
 132-191 3.15e-04

A domain family that is part of the cupin metalloenzyme superfamily; Probable enzymes, but of unknown functions, that regulate chromatin reorganisation processes (Clissold and Ponting, in press).


Pssm-ID: 214721  Cd Length: 58  Bit Score: 39.54  E-value: 3.15e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 310703680   132 CSNLPSELPQ---LLPDLESHVPWasealgkMPDAVNFWLGEAAAVTSLHKDHYE--NLYCVVSG 191
Cdd:smart00558   1 QLWNLAKLPFklnLLSDLPEDIPG-------PDVGPYLYMGMAGSTTPWHIDDYDlvNYLHQGAG 58
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
 243-347 3.52e-04

C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating protein 1), a Ras-specific GAP member, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA1 contains a C2 domain, a Ras-GAP domain, a pleckstrin homology (PH)-like domain, a SH3 domain, and 2 SH2 domains. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176045 [Multi-domain]  Cd Length: 126  Bit Score: 41.20  E-value: 3.52e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPsdcYVTLWLPTACSHRLQTRTVKNsssPVWNQSFHFRIHRQLKNVMELKVFDQDLVTGDDP 322
Cdd:cd08400    6 LQLNVLEAHKLPVKHVPHP---YCVISLNEVKVARTKVREGPN---PVWSEEFVFDDLPPDVNSFTISLSNKAKRSKDSE 79

                         90       100
                 ....*....|....*....|....*
gi 310703680 323 VLSVLFDAGTLRAGEFRRESFSLSP 347
Cdd:cd08400   80 IAEVTVQLSKLQNGQETDEWYPLSS 104
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 237-321 4.19e-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: 41.18  E-value: 4.19e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 237 VSRTCLLTVRVLQAHRLPSKDLVTPSDCYVTLWL-PTACSHRLQTRTVKNSS-SPVWNQSFHFRI-HRQL-KNVMELKVF 312
Cdd:cd08384    9 NTQRRGLIVGIIRCVNLAAMDANGYSDPFVKLYLkPDAGKKSKHKTQVKKKTlNPEFNEEFFYDIkHSDLaKKTLEITVW 88


                 ....*....
gi 310703680 313 DQDLVTGDD 321
Cdd:cd08384   89 DKDIGKSND 97
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 243-335 4.28e-04

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: 41.00  E-value: 4.28e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPS-DCYVTLWLpTACSHRLQTRTVKNSSSPVWNQSFHFRIHrQLKNVMELKVFDQDLVTGDD 321
Cdd:cd04044    4 LAVTIKSARGLKGSDIIGGTvDPYVTFSI-SNRRELARTKVKKDTSNPVWNETKYILVN-SLTEPLNLTVYDFNDKRKDK 81

                         90
                 ....*....|....
gi 310703680 322 PVLSVLFDAGTLRA 335
Cdd:cd04044   82 LIGTAEFDLSSLLQ 95
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 243-299 5.53e-04

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 40.70  E-value: 5.53e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 310703680 243 LTVRVLQAHRLPSKDL-VTPSDCYVTLWLPTACSHRLQTRTVKNSSSPVWNQSFHFRI 299
Cdd:cd08390   16 LTVSLIKARNLPPRTKdVAHCDPFVKVCLLPDERRSLQSKVKRKTQNPNFDETFVFQV 73
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
 245-321 7.03e-04

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. 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: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 40.51  E-value: 7.03e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 245 VRVLQAHRLPSKDLVTPSDCYVTLWLptaCSHRLQTRTVKNSSSPVWNQSFHFRIHRQLKN-----VMELKVFDQDLVTG 319
Cdd:cd08682    3 VTVLQARGLLCKGKSGTNDAYVIIQL---GKEKYSTSVKEKTTSPVWKEECSFELPGLLSGngnraTLQLTVMHRNLLGL 79


                 ..
gi 310703680 320 DD 321
Cdd:cd08682   80 DK 81
C2A_RasA2_RasA3 cd08401
C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase ...
 243-359 8.14e-04

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176046 [Multi-domain]  Cd Length: 121  Bit Score: 40.11  E-value: 8.14e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPS-KDLVTPSDCYVTLWLPTACSHRlqTRTVKNSSSPVWNQSFHFRIHRQLKNvMELKVFDQDLVTGDD 321
Cdd:cd08401    2 LKIKIGEAKNLPPrSGPNKMRDCYCTVNLDQEEVFR--TKTVEKSLCPFFGEDFYFEIPRTFRH-LSFYIYDRDVLRRDS 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 310703680 322 PVLSVLFDAGTLRAGEFRRESFSLSP-----QGEGRLEVEFRL 359
Cdd:cd08401   79 VIGKVAIKKEDLHKYYGKDTWFPLQPvdadsEVQGKVHLELRL 121
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 243-321 1.03e-03

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


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 39.91  E-value: 1.03e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWL-PTacsHR------LQTRTVKNSSSPVWNQSFHFRI---HRQLKNVMEL-KV 311
Cdd:cd04009   18 LRVEILNARNLLPLDSNGSSDPFVKVELlPR---HLfpdvptPKTQVKKKTLFPLFDESFEFNVppeQCSVEGALLLfTV 94

                         90
                 ....*....|
gi 310703680 312 FDQDLVTGDD 321
Cdd:cd04009   95 KDYDLLGSND 104
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 243-321 1.12e-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: 39.62  E-value: 1.12e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLwlptacSHRLQTRTVKNSS----SPVWNQSFHFRIHRQLKNVM---ELKVFDQD 315
Cdd:cd04049    3 LEVLLISAKGLQDTDFLGKIDPYVII------QCRTQERKSKVAKgdgrNPEWNEKFKFTVEYPGWGGDtklILRIMDKD 76


                 ....*.
gi 310703680 316 LVTGDD 321
Cdd:cd04049   77 NFSDDD 82
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 256-323 1.35e-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: 40.31  E-value: 1.35e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 310703680 256 KDLVTPsdcYVTLWLptaCSHRLQTRTVKNSSSPVWNQSFHFRIH-----RQLKnvmeLKVFDQDLVTGDDPV 323
Cdd:cd04018   32 KELVDP---YVEVSF---AGQKVKTSVKKNSYNPEWNEQIVFPEMfpplcERIK----IQIRDWDRVGNDDVI 94
C2_Freud-1 cd08690
C2 domain found in 5' repressor element under dual repression binding protein-1 (Freud-1); ...
 243-306 5.25e-03

C2 domain found in 5' repressor element under dual repression binding protein-1 (Freud-1); Freud-1 is a novel calcium-regulated repressor that negatively regulates basal 5-HT1A receptor expression in neurons. It may also play a role in the altered regulation of 5-HT1A receptors associated with anxiety or major depression. Freud-1 contains two DM-14 basic repeats, a helix-loop-helix DNA binding domain, and a C2 domain. The Freud-1 C2 domain is thought to be calcium insensitive and it lacks several acidic residues that mediate calcium binding of the PKC C2 domain. In addition, it contains a poly-basic insert that is not present in calcium-dependent C2 domains and may function as a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176072 [Multi-domain]  Cd Length: 155  Bit Score: 38.44  E-value: 5.25e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 310703680 243 LTVRVLQAHRLPS----KDLvtpsDCYVTLWLP----TACSHRlqTRTVKNSSSPVWNQSFHFRI---HRQLKNV 306
Cdd:cd08690    6 LTIVRCIGIPLPSgwnpKDL----DTYVKFEFPypneEPQSGK--TSTIKDTNSPEYNESFKLNInrkHRSFQRV 74
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 243-297 6.85e-03

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: 37.64  E-value: 6.85e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLW-LP-TACSHRLQTRTVKNSSSPVWNQSFHF 297
Cdd:cd04030   18 LIVTVHKCRNLPPCDSSDIPDPYVRLYlLPdKSKSTRRKTSVKKDNLNPVFDETFEF 74
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 244-321 7.86e-03

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 37.14  E-value: 7.86e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 244 TVR--VLQAHRLPSKDLVTPSDCYVTLWLPtacSHRLQTR--TVKNSSSPVWNQSFHFRIHRQLKNVMELKVFDQDLVTG 319
Cdd:cd04037    1 LVRvyVVRARNLQPKDPNGKSDPYLKIKLG---KKKINDRdnYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGS 77


                 ..
gi 310703680 320 DD 321
Cdd:cd04037   78 DD 79
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 243-338 8.10e-03

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


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 37.74  E-value: 8.10e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTpSDCYVTL-WLPTACSHRLQTRTVKNSSSPVWNQSFHFRIHRqlKNVMELKVFDQDLVTGDD 321
Cdd:cd08675    1 LSVRVLECRDLALKSNGT-CDPFARVtLNYSSKTDTKRTKVKKKTNNPRFDEAFYFELTI--GFSYEKKSFKVEEEDLEK 77

                         90
                 ....*....|....*...
gi 310703680 322 PVLSV-LFDAGTLRAGEF 338
Cdd:cd08675   78 SELRVeLWHASMVSGDDF 95
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 243-323 9.54e-03

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 37.38  E-value: 9.54e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310703680 243 LTVRVLQAHRLPSKDLVTPSDCYVTLWLPTAcSHRL---QTRTVKNSSSPVWNQSFHFRI-HRQLKNV-MELKVFDQDLV 317
Cdd:cd08402   17 LTVVILEAKNLKKMDVGGLSDPYVKIHLMQN-GKRLkkkKTTIKKRTLNPYYNESFSFEVpFEQIQKVhLIVTVLDYDRI 95


                 ....*.
gi 310703680 318 TGDDPV 323
Cdd:cd08402   96 GKNDPI 101
 
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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