NCBI Conserved Domain Search

Conserved domains on [gi|35493853|ref|NP_919303|]

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otoferlin isoform c [Homo sapiens]

Protein Classification

C2D_Ferlin and C2F_Ferlin domain-containing protein( domain architecture ID 11173639)

protein containing domains FerB, C2D_Ferlin, C2E_Ferlin, and C2F_Ferlin

Graphical summary

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List of domain hits

Name

Accession

Description

Interval

E-value

C2F_Ferlin

cd08374

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

1043-1176

2.03e-76

C2 domain sixth 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 sixth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176020 Cd Length: 133 Bit Score: 248.35 E-value: 2.03e-76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853 1043 ELRVIIWNTDEVvLEDDDFFTGEKSSDIFVRGWLKGQQEDKQDTDVHYHSLTGEGNFNWRYLFPFDYLAAEEKIVISKKE 1122
Cdd:cd08374    1 ELRVIVWNTRDV-LNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKE 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 35493853 1123 SMFSWDETEYKIPARLTLQIWDADHFSADDFLGAIELDLNRFPRGAKTAKQCTM 1176
Cdd:cd08374   80 HFWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133

C2D_Ferlin

cd04017

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

270-407

1.56e-72

C2 domain fourth 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 fourth C2 repeat, C2D, and has a type-II topology.

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 237.44 E-value: 1.56e-72

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  270 FQLRAHMYQARSLFAADSSGLSDPFARVFFINQSQCTEVLNETLCPTWDQMLVFDNLELYGEAHELRDDPPIIVIEIYDQ 349
Cdd:cd04017    1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 35493853  350 DSMGKADFMGRTFAKPLVKMADEaycpPRFPPQLEYYQIYRGNATAGDLLAAFELLQI 407
Cdd:cd04017   81 DSVGKDEFLGRSVAKPLVKLDLE----EDFPPKLQWFPIYKGGQSAGELLAAFELIEV 134

C2E_Ferlin

cd04037

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

803-926

2.31e-70

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: 230.90 E-value: 2.31e-70

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  803 LVRVYVVRATDLHPADINGKADPYIAIRLGKTDIRDKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDL 882
Cdd:cd04037    1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 35493853  883 IGETKIDLENRFYSKHRATCGIAQTYSTHGYNIWRDPMKPSQIL 926
Cdd:cd04037   81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124

FerB

pfam08150

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

152-227

3.70e-43

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

Pssm-ID: 462376 Cd Length: 76 Bit Score: 151.21 E-value: 3.70e-43

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 35493853    152 PQHSIPDIFIWMMSNNKRVAYARVPSKDLLFSIVEEETGKDCAKVKTLFLKLPGKRGFGSAGWTVQAKVELYLWLG 227
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPVEEERGKFCGKVQTLFLKYPGKKAKGPAGWEIPAKLRVYLWLG 76

Ferlin_C super family

cl24672

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...

1186-1274

2.45e-34

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin family, including dysferlin, myoferlin, otoferlin and fer-1-like proteins.

The actual alignment was detected with superfamily member pfam16165:

Pssm-ID: 435183 Cd Length: 154 Bit Score: 129.12 E-value: 2.45e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853   1186 PLVSIFKQKRVKGWWPLLARNENDEFE-----------------------------------LTGKVEAELHLLTAEEAE 1230
Cdd:pfam16165    1 PRVSIFRAKRMKGWWPFIKLKSQEDFEreereakkkkkkknkrsekkpedlefkdasgntflLMGKVEAEFELLTVEEAE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 35493853   1231 KNPVGLARNEPDPLEKPNRPDTSFIWFLNPLKSARYFLWHTYRW 1274
Cdd:pfam16165   81 KSPVGKGRKEPEPLEKPNRPKTSFSWFVNPMKTFIFFIWRRYKK 124

C2 super family

cl14603

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

453-530

6.05e-03

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.

The actual alignment was detected with superfamily member cd04011:

Pssm-ID: 472691 [Multi-domain] Cd Length: 111 Bit Score: 37.94 E-value: 6.05e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 35493853  453 RDLKRVNLaqvdRPRVDIECAGKGvQSSLIHNYKKNPNFN-TLVkwFEVDLPENELLHPPLNIRVVDCRAFGRYTLVGS 530
Cdd:cd04011   14 RQLVGGNI----DPVVKVEVGGQK-KYTSVKKGTNCPFYNeYFF--FNFHESPDELFDKIIKISVYDSRSLRSDTLIGS 85

Name

Accession

Description

Interval

E-value

C2F_Ferlin

cd08374

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

1043-1176

2.03e-76

Pssm-ID: 176020 Cd Length: 133 Bit Score: 248.35 E-value: 2.03e-76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853 1043 ELRVIIWNTDEVvLEDDDFFTGEKSSDIFVRGWLKGQQEDKQDTDVHYHSLTGEGNFNWRYLFPFDYLAAEEKIVISKKE 1122
Cdd:cd08374    1 ELRVIVWNTRDV-LNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKE 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 35493853 1123 SMFSWDETEYKIPARLTLQIWDADHFSADDFLGAIELDLNRFPRGAKTAKQCTM 1176
Cdd:cd08374   80 HFWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133

C2D_Ferlin

cd04017

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

270-407

1.56e-72

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 237.44 E-value: 1.56e-72

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  270 FQLRAHMYQARSLFAADSSGLSDPFARVFFINQSQCTEVLNETLCPTWDQMLVFDNLELYGEAHELRDDPPIIVIEIYDQ 349
Cdd:cd04017    1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 35493853  350 DSMGKADFMGRTFAKPLVKMADEaycpPRFPPQLEYYQIYRGNATAGDLLAAFELLQI 407
Cdd:cd04017   81 DSVGKDEFLGRSVAKPLVKLDLE----EDFPPKLQWFPIYKGGQSAGELLAAFELIEV 134

C2E_Ferlin

cd04037

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

803-926

2.31e-70

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 230.90 E-value: 2.31e-70

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  803 LVRVYVVRATDLHPADINGKADPYIAIRLGKTDIRDKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDL 882
Cdd:cd04037    1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 35493853  883 IGETKIDLENRFYSKHRATCGIAQTYSTHGYNIWRDPMKPSQIL 926
Cdd:cd04037   81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124

FerB

pfam08150

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

152-227

3.70e-43

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

Pssm-ID: 462376 Cd Length: 76 Bit Score: 151.21 E-value: 3.70e-43

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 35493853    152 PQHSIPDIFIWMMSNNKRVAYARVPSKDLLFSIVEEETGKDCAKVKTLFLKLPGKRGFGSAGWTVQAKVELYLWLG 227
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPVEEERGKFCGKVQTLFLKYPGKKAKGPAGWEIPAKLRVYLWLG 76

Ferlin_C

pfam16165

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...

1186-1274

2.45e-34

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin family, including dysferlin, myoferlin, otoferlin and fer-1-like proteins.

Pssm-ID: 435183 Cd Length: 154 Bit Score: 129.12 E-value: 2.45e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853   1186 PLVSIFKQKRVKGWWPLLARNENDEFE-----------------------------------LTGKVEAELHLLTAEEAE 1230
Cdd:pfam16165    1 PRVSIFRAKRMKGWWPFIKLKSQEDFEreereakkkkkkknkrsekkpedlefkdasgntflLMGKVEAEFELLTVEEAE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 35493853   1231 KNPVGLARNEPDPLEKPNRPDTSFIWFLNPLKSARYFLWHTYRW 1274
Cdd:pfam16165   81 KSPVGKGRKEPEPLEKPNRPKTSFSWFVNPMKTFIFFIWRRYKK 124

pfam00168

C2 domain;

803-899

1.76e-20

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 87.76 E-value: 1.76e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853    803 LVRVYVVRATDLHPADINGKADPYIAIRLGKTDIRDKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDL 882
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDDF 81

                           90
                   ....*....|....*..
gi 35493853    883 IGETKIDLENRFYSKHR 899
Cdd:pfam00168   82 IGEVRIPLSELDSGEGL 98

smart00239

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

803-892

1.15e-17

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

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 79.45 E-value: 1.15e-17

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853     803 LVRVYVVRATDLHPADINGKADPYIAIRLGKTD-IRDKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDD 881
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPkEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                            90
                    ....*....|.
gi 35493853     882 LIGETKIDLEN 892
Cdd:smart00239   81 FIGQVTIPLSD 91

pfam00168

C2 domain;

271-361

7.95e-14

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 68.50 E-value: 7.95e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853    271 QLRAHMYQARSLFAADSSGLSDPFARVFFI--NQSQCTEVLNETLCPTWDQMLVFdnlelygEAHELRDDPpiIVIEIYD 348
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTF-------SVPDPENAV--LEIEVYD 72

                           90
                   ....*....|...
gi 35493853    349 QDSMGKADFMGRT 361
Cdd:pfam00168   73 YDRFGRDDFIGEV 85

COG5038

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

806-893

7.39e-12

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 70.17 E-value: 7.39e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRLGKTDIRdKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDLIGE 885
Cdd:COG5038 1044 IMLRSGENLPSSDENGYSDPFVKLFLNEKSVY-KTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDLLGT 1122


                 ....*...
gi 35493853  886 TKIDLENR 893
Cdd:COG5038 1123 AEIDLSKL 1130

smart00239

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

271-361

7.82e-12

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 62.89 E-value: 7.82e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853     271 QLRAHMYQARSLFAADSSGLSDPFARVFFINQ---SQCTEVLNETLCPTWDQMLVFDnlelygeahELRDDPPIIVIEIY 347
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFE---------VPPPELAELEIEVY 71

                            90
                    ....*....|....
gi 35493853     348 DQDSMGKADFMGRT 361
Cdd:smart00239   72 DKDRFGRDDFIGQV 85

smart00239

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

1067-1170

3.38e-05

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 44.02 E-value: 3.38e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853    1067 SSDIFVRGWLKGQQEDKQDTDVHYHSLtgegNFNWRYLFPFDYLAAEEkiviskkesmfswdeteykipARLTLQIWDAD 1146
Cdd:smart00239   20 KSDPYVKVSLDGDPKEKKKTKVVKNTL----NPVWNETFEFEVPPPEL---------------------AELEIEVYDKD 74

                            90       100
                    ....*....|....*....|....
gi 35493853    1147 HFSADDFLGAIELDLNRFPRGAKT 1170
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLLLGGRH 98

pfam00168

C2 domain;

1127-1167

4.37e-04

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 40.77 E-value: 4.37e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 35493853   1127 WDET-EYKIP----ARLTLQIWDADHFSADDFLGAIELDLNRFPRG 1167
Cdd:pfam00168   50 WNETfTFSVPdpenAVLEIEVYDYDRFGRDDFIGEVRIPLSELDSG 95

C2B_Ferlin

cd04011

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

453-530

6.05e-03

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

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 37.94 E-value: 6.05e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 35493853  453 RDLKRVNLaqvdRPRVDIECAGKGvQSSLIHNYKKNPNFN-TLVkwFEVDLPENELLHPPLNIRVVDCRAFGRYTLVGS 530
Cdd:cd04011   14 RQLVGGNI----DPVVKVEVGGQK-KYTSVKKGTNCPFYNeYFF--FNFHESPDELFDKIIKISVYDSRSLRSDTLIGS 85

Name

Accession

Description

Interval

E-value

C2F_Ferlin

cd08374

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

1043-1176

2.03e-76

Pssm-ID: 176020 Cd Length: 133 Bit Score: 248.35 E-value: 2.03e-76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853 1043 ELRVIIWNTDEVvLEDDDFFTGEKSSDIFVRGWLKGQQEDKQDTDVHYHSLTGEGNFNWRYLFPFDYLAAEEKIVISKKE 1122
Cdd:cd08374    1 ELRVIVWNTRDV-LNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKE 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 35493853 1123 SMFSWDETEYKIPARLTLQIWDADHFSADDFLGAIELDLNRFPRGAKTAKQCTM 1176
Cdd:cd08374   80 HFWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133

C2D_Ferlin

cd04017

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

270-407

1.56e-72

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 237.44 E-value: 1.56e-72

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  270 FQLRAHMYQARSLFAADSSGLSDPFARVFFINQSQCTEVLNETLCPTWDQMLVFDNLELYGEAHELRDDPPIIVIEIYDQ 349
Cdd:cd04017    1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 35493853  350 DSMGKADFMGRTFAKPLVKMADEaycpPRFPPQLEYYQIYRGNATAGDLLAAFELLQI 407
Cdd:cd04017   81 DSVGKDEFLGRSVAKPLVKLDLE----EDFPPKLQWFPIYKGGQSAGELLAAFELIEV 134

C2E_Ferlin

cd04037

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

803-926

2.31e-70

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 230.90 E-value: 2.31e-70

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  803 LVRVYVVRATDLHPADINGKADPYIAIRLGKTDIRDKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDL 882
Cdd:cd04037    1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 35493853  883 IGETKIDLENRFYSKHRATCGIAQTYSTHGYNIWRDPMKPSQIL 926
Cdd:cd04037   81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124

FerB

pfam08150

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

152-227

3.70e-43

FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.

Pssm-ID: 462376 Cd Length: 76 Bit Score: 151.21 E-value: 3.70e-43

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 35493853    152 PQHSIPDIFIWMMSNNKRVAYARVPSKDLLFSIVEEETGKDCAKVKTLFLKLPGKRGFGSAGWTVQAKVELYLWLG 227
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPVEEERGKFCGKVQTLFLKYPGKKAKGPAGWEIPAKLRVYLWLG 76

Ferlin_C

pfam16165

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...

1186-1274

2.45e-34

Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin family, including dysferlin, myoferlin, otoferlin and fer-1-like proteins.

Pssm-ID: 435183 Cd Length: 154 Bit Score: 129.12 E-value: 2.45e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853   1186 PLVSIFKQKRVKGWWPLLARNENDEFE-----------------------------------LTGKVEAELHLLTAEEAE 1230
Cdd:pfam16165    1 PRVSIFRAKRMKGWWPFIKLKSQEDFEreereakkkkkkknkrsekkpedlefkdasgntflLMGKVEAEFELLTVEEAE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 35493853   1231 KNPVGLARNEPDPLEKPNRPDTSFIWFLNPLKSARYFLWHTYRW 1274
Cdd:pfam16165   81 KSPVGKGRKEPEPLEKPNRPKTSFSWFVNPMKTFIFFIWRRYKK 124

cd00030

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

804-892

7.80e-21

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 88.66 E-value: 7.80e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPADINGKADPYIAIRLGKTDIRdKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDLI 883
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKF-KTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDFL 79


                 ....*....
gi 35493853  884 GETKIDLEN 892
Cdd:cd00030   80 GEVEIPLSE 88

pfam00168

C2 domain;

803-899

1.76e-20

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 87.76 E-value: 1.76e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853    803 LVRVYVVRATDLHPADINGKADPYIAIRLGKTDIRDKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDL 882
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDDF 81

                           90
                   ....*....|....*..
gi 35493853    883 IGETKIDLENRFYSKHR 899
Cdd:pfam00168   82 IGEVRIPLSELDSGEGL 98

C2D_Tricalbin-like

cd04040

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

804-890

4.35e-18

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: 81.08 E-value: 4.35e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPADINGKADPYIAIRLG-----KTDIrdkenyISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVG 878
Cdd:cd04040    1 LTVDVISAENLPSADRNGKSDPFVKFYLNgekvfKTKT------IKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGG 74

                         90
                 ....*....|..
gi 35493853  879 TDDLIGETKIDL 890
Cdd:cd04040   75 KDDLLGSAYIDL 86

smart00239

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

803-892

1.15e-17

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 79.45 E-value: 1.15e-17

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853     803 LVRVYVVRATDLHPADINGKADPYIAIRLGKTD-IRDKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDD 881
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPkEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                            90
                    ....*....|.
gi 35493853     882 LIGETKIDLEN 892
Cdd:smart00239   81 FIGQVTIPLSD 91

pfam00168

C2 domain;

271-361

7.95e-14

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 68.50 E-value: 7.95e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853    271 QLRAHMYQARSLFAADSSGLSDPFARVFFI--NQSQCTEVLNETLCPTWDQMLVFdnlelygEAHELRDDPpiIVIEIYD 348
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTF-------SVPDPENAV--LEIEVYD 72

                           90
                   ....*....|...
gi 35493853    349 QDSMGKADFMGRT 361
Cdd:pfam00168   73 YDRFGRDDFIGEV 85

cd00030

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

272-361

1.00e-13

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 68.25 E-value: 1.00e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  272 LRAHMYQARSLFAADSSGLSDPFARVFFIN-QSQCTEVLNETLCPTWDQMLVFDNLElygeahelrDDPPIIVIEIYDQD 350
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGkQKFKTKVVKNTLNPVWNETFEFPVLD---------PESDTLTVEVWDKD 71

                         90
                 ....*....|.
gi 35493853  351 SMGKADFMGRT 361
Cdd:cd00030   72 RFSKDDFLGEV 82

C2B_RasA1_RasA4

cd04025

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

272-360

1.89e-13

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: 68.28 E-value: 1.89e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  272 LRAHMYQARSLFAADSSGLSDPFARVFFINQSQCTEVLNETLCPTWDQMLVFdnlelygeahELRDDPP-IIVIEIYDQD 350
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEF----------ELMEGADsPLSVEVWDWD 71

                         90
                 ....*....|
gi 35493853  351 SMGKADFMGR 360
Cdd:cd04025   72 LVSKNDFLGK 81

COG5038

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

806-893

7.39e-12

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 70.17 E-value: 7.39e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRLGKTDIRdKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDLIGE 885
Cdd:COG5038 1044 IMLRSGENLPSSDENGYSDPFVKLFLNEKSVY-KTKVVKKTLNPVWNEEFTIEVLNRVKDVLTINVNDWDSGEKNDLLGT 1122


                 ....*...
gi 35493853  886 TKIDLENR 893
Cdd:COG5038 1123 AEIDLSKL 1130

smart00239

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

271-361

7.82e-12

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 62.89 E-value: 7.82e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853     271 QLRAHMYQARSLFAADSSGLSDPFARVFFINQ---SQCTEVLNETLCPTWDQMLVFDnlelygeahELRDDPPIIVIEIY 347
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFE---------VPPPELAELEIEVY 71

                            90
                    ....*....|....
gi 35493853     348 DQDSMGKADFMGRT 361
Cdd:smart00239   72 DKDRFGRDDFIGQV 85

C2B_Munc13-like

cd04009

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

797-892

2.21e-11

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: 62.64 E-value: 2.21e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  797 NDPINVLvRVYVVRATDLHPADINGKADPYIAIRLGKTDI-----RDKENYISKQLNPVFGKSFDIeaSFPME------S 865
Cdd:cd04009   12 RASEQSL-RVEILNARNLLPLDSNGSSDPFVKVELLPRHLfpdvpTPKTQVKKKTLFPLFDESFEF--NVPPEqcsvegA 88

                         90       100
                 ....*....|....*....|....*..
gi 35493853  866 MLTVAVYDWDLVGTDDLIGETKIDLEN 892
Cdd:cd04009   89 LLLFTVKDYDLLGSNDFEGEAFLPLND 115

C2A_Synaptotagmin-like

cd04024

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

805-894

3.27e-11

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: 62.06 E-value: 3.27e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  805 RVYVVRATDLHPADI--NGKADPYIAIRLGktDIRDKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDL 882
Cdd:cd04024    4 RVHVVEAKDLAAKDRsgKGKSDPYAILSVG--AQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKDY 81

                         90
                 ....*....|..
gi 35493853  883 IGETKIDLENRF 894
Cdd:cd04024   82 LGEFDIALEEVF 93

C2_Munc13_fungal

cd04043

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...

808-896

4.10e-11

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: 61.51 E-value: 4.10e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  808 VVRATDLHPADINGKADPYIAI-------RLGKTDIrdkenyISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTD 880
Cdd:cd04043    7 IVRAENLKADSSNGLSDPYVTLvdtngkrRIAKTRT------IYDTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKH 80

                         90
                 ....*....|....*.
gi 35493853  881 DLIGETKIDLENRFYS 896
Cdd:cd04043   81 DLCGRASLKLDPKRFG 96

C2A_RIM1alpha

cd04031

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

806-892

2.14e-10

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: 59.57 E-value: 2.14e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRL----GKTDIRDKEnYISKQLNPVFGKSF---DIEASFPMESMLTVAVYDWDLVG 878
Cdd:cd04031   20 VTVLQARDLPPRDDGSLRNPYVKVYLlpdrSEKSKRRTK-TVKKTLNPEWNQTFeysNVRRETLKERTLEVTVWDYDRDG 98

                         90
                 ....*....|....
gi 35493853  879 TDDLIGETKIDLEN 892
Cdd:cd04031   99 ENDFLGEVVIDLAD 112

C2C_MCTP_PRT

cd08377

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

806-890

2.44e-10

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

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 59.24 E-value: 2.44e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRLGKTdiRDKENYISKQLNPVFGKSFdieaSFP---MESMLTVAVYDWDLVGTDDL 882
Cdd:cd08377    5 VKVIRASGLAAADIGGKSDPFCVLELVNA--RLQTHTIYKTLNPEWNKIF----TFPikdIHDVLEVTVYDEDKDKKPEF 78


                 ....*...
gi 35493853  883 IGETKIDL 890
Cdd:cd08377   79 LGKVAIPL 86

C2_PKC_alpha_gamma

cd04026

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...

806-884

3.10e-10

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: 59.20 E-value: 3.10e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRLG---KTDIRDKENYISKQLNPVFGKSFDIEASfP--MESMLTVAVYDWDLVGTD 880
Cdd:cd04026   17 VEVREAKNLIPMDPNGLSDPYVKLKLIpdpKNETKQKTKTIKKTLNPVWNETFTFDLK-PadKDRRLSIEVWDWDRTTRN 95


                 ....
gi 35493853  881 DLIG 884
Cdd:cd04026   96 DFMG 99

C2B_RasA1_RasA4

cd04025

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

804-891

4.17e-10

Pssm-ID: 175991 [Multi-domain] Cd Length: 123 Bit Score: 58.65 E-value: 4.17e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPADINGKADPYIAIRL-GKTDirdKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDL 882
Cdd:cd04025    2 LRCHVLEARDLAPKDRNGTSDPFVRVFYnGQTL---ETSVVKKSCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKNDF 78


                 ....*....
gi 35493853  883 IGETKIDLE 891
Cdd:cd04025   79 LGKVVFSIQ 87

C2B_Synaptotagmin-7

cd08405

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

799-893

1.95e-09

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: 57.04 E-value: 1.95e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  799 PINVLVRVYVVRATDLHPADINGKADPYIAIRLGKTDIR--DKENYISKQ-LNPVFGKSF--DIEASFPMESMLTVAVYD 873
Cdd:cd08405   12 PTANRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRveKKKTVIKKRtLNPVFNESFifNIPLERLRETTLIITVMD 91

                         90       100
                 ....*....|....*....|
gi 35493853  874 WDLVGTDDLIGetKIDLENR 893
Cdd:cd08405   92 KDRLSRNDLIG--KIYLGWK 109

C2B_MCTP_PRT

cd08376

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

803-892

2.88e-09

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

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 56.11 E-value: 2.88e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  803 LVRVYVVRATDLHPADINGKADPYIAIRLGktdirdKENYISK----QLNPVFGKSFDI----EASfpmeSMLTVAVYDW 874
Cdd:cd08376    1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRLG------NEKYKSKvcskTLNPQWLEQFDLhlfdDQS----QILEIEVWDK 70

                         90
                 ....*....|....*...
gi 35493853  875 DLVGTDDLIGETKIDLEN 892
Cdd:cd08376   71 DTGKKDEFIGRCEIDLSA 88

C2_ArfGAP

cd04038

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...

803-900

3.68e-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: 56.57 E-value: 3.68e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  803 LVRVYVVRATDLHPADINGkADPYIAIRLGKTDIRDKenYISKQLNPVFgksfDIEASFPMESM---LTVAVYDWDLVGT 879
Cdd:cd04038    3 LLKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTR--VIKKNLNPVW----NEELTLSVPNPmapLKLEVFDKDTFSK 75

                         90       100
                 ....*....|....*....|.
gi 35493853  880 DDLIGETKIDLENrFYSKHRA 900
Cdd:cd04038   76 DDSMGEAEIDLEP-LVEAAKL 95

C2A_MCTP_PRT

cd04042

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

803-892

8.91e-09

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: 54.97 E-value: 8.91e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  803 LVRVYVVRATDLHPADINGKADPYIAIRLGktdirDKENY----ISKQLNPVFGKSFdieaSFPMESM---LTVAVYDWD 875
Cdd:cd04042    1 QLDIHLKEGRNLAARDRGGTSDPYVKFKYG-----GKTVYksktIYKNLNPVWDEKF----TLPIEDVtqpLYIKVFDYD 71

                         90
                 ....*....|....*..
gi 35493853  876 LVGTDDLIGETKIDLEN 892
Cdd:cd04042   72 RGLTDDFMGSAFVDLST 88

C2B_Synaptotagmin-1

cd08402

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

806-885

1.35e-08

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: 54.71 E-value: 1.35e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRL--GKTDIRDKENYISKQ-LNPVFGKSFDIEASFPM--ESMLTVAVYDWDLVGTD 880
Cdd:cd08402   19 VVILEAKNLKKMDVGGLSDPYVKIHLmqNGKRLKKKKTTIKKRtLNPYYNESFSFEVPFEQiqKVHLIVTVLDYDRIGKN 98


                 ....*
gi 35493853  881 DLIGE 885
Cdd:cd08402   99 DPIGK 103

C2C_MCTP_PRT

cd08377

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

279-368

1.37e-08

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 54.23 E-value: 1.37e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  279 ARSLFAADSSGLSDPFARVFFINQSQCTEVLNETLCPTWDQMLVFdnlelygeahELRDDPPIIVIEIYDQDSMGKADFM 358
Cdd:cd08377   10 ASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTF----------PIKDIHDVLEVTVYDEDKDKKPEFL 79

                         90
                 ....*....|
gi 35493853  359 GRTfAKPLVK 368
Cdd:cd08377   80 GKV-AIPLLS 88

C2A_Synaptotagmin-1-5-6-9-10

cd08385

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

806-890

1.45e-08

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: 54.19 E-value: 1.45e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRL---GKTDIRDKENYisKQLNPVFGKSFDIEASFP--MESMLTVAVYDWDLVGTD 880
Cdd:cd08385   20 VGIIQAADLPAMDMGGTSDPYVKVYLlpdKKKKFETKVHR--KTLNPVFNETFTFKVPYSelGNKTLVFSVYDFDRFSKH 97

                         90
                 ....*....|
gi 35493853  881 DLIGETKIDL 890
Cdd:cd08385   98 DLIGEVRVPL 107

C2_Intersectin

cd08375

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...

262-361

1.78e-08

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 54.31 E-value: 1.78e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  262 LVYTKKQAF--QLRAHMYQARSLFAADSSGLSDPFARVFFINQSQCTEVLNETLCPTWD---QMLVFDnlelygeaheLR 336
Cdd:cd08375    5 LARSQRASGigRLMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNssmQFFVKD----------LE 74

                         90       100
                 ....*....|....*....|....*
gi 35493853  337 DDppIIVIEIYDQDSMGKADFMGRT 361
Cdd:cd08375   75 QD--VLCITVFDRDFFSPDDFLGRT 97

C2A_RIM1alpha

cd04031

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

260-372

1.93e-08

Pssm-ID: 175997 [Multi-domain] Cd Length: 125 Bit Score: 53.79 E-value: 1.93e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  260 VSLVYTKKQAfQLRAHMYQARSLFAADSSGLSDPFARVFFI------NQSQcTEVLNETLCPTWDQMLVFDNLelygEAH 333
Cdd:cd04031    7 IQLWYDKVTS-QLIVTVLQARDLPPRDDGSLRNPYVKVYLLpdrsekSKRR-TKTVKKTLNPEWNQTFEYSNV----RRE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 35493853  334 ELRDDppiiVIEI--YDQDSMGKADFMGRTfakpLVKMADE 372
Cdd:cd04031   81 TLKER----TLEVtvWDYDRDGENDFLGEV----VIDLADA 113

C2B_Synaptotagmin-3-5-6-9-10

cd08403

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...

806-922

1.95e-08

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 54.44 E-value: 1.95e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRL---GKTdIRDKENYISKQ-LNPVFGKS--FDIeasfPMESM----LTVAVYDWD 875
Cdd:cd08403   18 LTIIKARNLKAMDITGFSDPYVKVSLmceGRR-LKKKKTSVKKNtLNPTYNEAlvFDV----PPENVdnvsLIIAVVDYD 92

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 35493853  876 LVGTDDLIGetkidlenrfyskhraTCGIAQTYSTHGYNIWRD----PMKP 922
Cdd:cd08403   93 RVGHNELIG----------------VCRVGPNADGQGREHWNEmlanPRKP 127

C2B_RasGAP

cd08675

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

272-360

2.65e-08

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: 53.92 E-value: 2.65e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  272 LRAHMYQARSLfAADSSGLSDPFARVFFI----NQSQCTEVLNETLCPTWDQMLVFD-----NLELYGEAHELRD-DPPI 341
Cdd:cd08675    1 LSVRVLECRDL-ALKSNGTCDPFARVTLNysskTDTKRTKVKKKTNNPRFDEAFYFEltigfSYEKKSFKVEEEDlEKSE 79

                         90
                 ....*....|....*....
gi 35493853  342 IVIEIYDQDSMGKADFMGR 360
Cdd:cd08675   80 LRVELWHASMVSGDDFLGE 98

C2B_Ferlin

cd04011

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

267-359

3.08e-08

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 52.96 E-value: 3.08e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  267 KQAFQLRAHMYQARSLfaadSSGLSDPFARVFFINQSQCTEVLNETLCPTWDQMLVFDnleLYGEAHELRDDppIIVIEI 346
Cdd:cd04011    1 PQDFQVRVRVIEARQL----VGGNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFN---FHESPDELFDK--IIKISV 71

                         90
                 ....*....|...
gi 35493853  347 YDQDSMGKADFMG 359
Cdd:cd04011   72 YDSRSLRSDTLIG 84

C2D_Tricalbin-like

cd04040

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

279-361

8.59e-08

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 51.80 E-value: 8.59e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  279 ARSLFAADSSGLSDPFArVFFINQSQC--TEVLNETLCPTWDQMLVFDNLELYgeahelRDDppiIVIEIYDQDSMGKAD 356
Cdd:cd04040    8 AENLPSADRNGKSDPFV-KFYLNGEKVfkTKTIKKTLNPVWNESFEVPVPSRV------RAV---LKVEVYDWDRGGKDD 77


                 ....*
gi 35493853  357 FMGRT 361
Cdd:cd04040   78 LLGSA 82

C2A_C2C_Synaptotagmin_like

cd08391

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

272-361

8.76e-08

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: 51.91 E-value: 8.76e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  272 LRAHMYQARSLFAAD------SSGLSDPFARVFFINQSQCTEVLNETLCPTWDQM--LVFDNLElyGEAhelrddppiIV 343
Cdd:cd08391    3 LRIHVIEAQDLVAKDkfvgglVKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVyeAVVDEVP--GQE---------LE 71

                         90
                 ....*....|....*...
gi 35493853  344 IEIYDQDsMGKADFMGRT 361
Cdd:cd08391   72 IELFDED-PDKDDFLGRL 88

C2A_Synaptotagmin-8

cd08387

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

790-892

1.03e-07

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: 52.02 E-value: 1.03e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  790 MFQGIPSNDPINVLvRVYVVRATDLHPADINGKADPYIAIRLGKTDIRDKENYISKQ-LNPVFGKSFDIEASfPME---S 865
Cdd:cd08387    5 LHFSLEYDKDMGIL-NVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNTKQSKIHKKtLNPEFDESFVFEVP-PQElpkR 82

                         90       100
                 ....*....|....*....|....*..
gi 35493853  866 MLTVAVYDWDLVGTDDLIGETKIDLEN 892
Cdd:cd08387   83 TLEVLLYDFDQFSRDECIGVVELPLAE 109

C2A_Synaptotagmin-7

cd08386

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...

806-892

1.34e-07

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: 51.56 E-value: 1.34e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRLgktdIRDKENYIS-----KQLNPVFGKSFDIEAsFPMESM----LTVAVYDWDL 876
Cdd:cd08386   20 LKILKAVELPAKDFSGTSDPFVKIYL----LPDKKHKLEtkvkrKNLNPHWNETFLFEG-FPYEKLqqrvLYLQVLDYDR 94

                         90
                 ....*....|....*.
gi 35493853  877 VGTDDLIGETKIDLEN 892
Cdd:cd08386   95 FSRNDPIGEVSLPLNK 110

C2A_Rabphilin_Doc2

cd04035

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

798-892

1.67e-07

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

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 51.13 E-value: 1.67e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  798 DPINVLVRVYVVRATDLHPADINGKADPYIAIRL-----GKTDIRDKEnyISKQLNPVFGKSF---DIEASFPMESMLTV 869
Cdd:cd04035   11 DPANSALHCTIIRAKGLKAMDANGLSDPYVKLNLlpgasKATKLRTKT--VHKTRNPEFNETLtyyGITEEDIQRKTLRL 88

                         90       100
                 ....*....|....*....|...
gi 35493853  870 AVYDWDLVGtDDLIGETKIDLEN 892
Cdd:cd04035   89 LVLDEDRFG-NDFLGETRIPLKK 110

C2A_C2C_Synaptotagmin_like

cd08391

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

803-891

1.69e-07

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 51.14 E-value: 1.69e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  803 LVRVYVVRATDLHPADIN------GKADPYIAIRLGKTDIRDKenYISKQLNPVFGKSFdiEASFPMES--MLTVAVYDW 874
Cdd:cd08391    2 VLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRVGAQTFKSK--VIKENLNPKWNEVY--EAVVDEVPgqELEIELFDE 77

                         90
                 ....*....|....*..
gi 35493853  875 DlVGTDDLIGETKIDLE 891
Cdd:cd08391   78 D-PDKDDFLGRLSIDLG 93

C2C_Tricalbin-like

cd04045

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

804-892

1.95e-07

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 51.05 E-value: 1.95e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPADINGKADPYIAIRLGKTdIRDKENYISKQLNPVFGKSFDIEASFPMESmLTVAVYDWDLVGTDDLI 883
Cdd:cd04045    3 LRLHIRKANDLKNLEGVGKIDPYVRVLVNGI-VKGRTVTISNTLNPVWDEVLYVPVTSPNQK-ITLEVMDYEKVGKDRSL 80


                 ....*....
gi 35493853  884 GETKIDLEN 892
Cdd:cd04045   81 GSVEINVSD 89

C2_NEDD4_NEDD4L

cd04033

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

803-908

3.08e-07

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175999 [Multi-domain] Cd Length: 133 Bit Score: 50.81 E-value: 3.08e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  803 LVRVYVVRATDLHPADINGKADPYIAIRLGKTDiRDKE------NYISKQLNPVFGKSFDIEASfPMESMLTVAVYDWDL 876
Cdd:cd04033    1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPD-GNGEidsvqtKTIKKTLNPKWNEEFFFRVN-PREHRLLFEVFDENR 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 35493853  877 VGTDDLIGETKIDLENRFYSKHRATCGIAQTY 908
Cdd:cd04033   79 LTRDDFLGQVEVPLNNLPTETPGNERRYTFKD 110

C2B_Munc13-like

cd04009

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

279-362

3.15e-07

Pssm-ID: 175976 [Multi-domain] Cd Length: 133 Bit Score: 50.70 E-value: 3.15e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  279 ARSLFAADSSGLSDPFARV-------FFINQSQCTEVLNETLCPTWDQMLVFdnlELYGEAHELRDdpPIIVIEIYDQDS 351
Cdd:cd04009   25 ARNLLPLDSNGSSDPFVKVellprhlFPDVPTPKTQVKKKTLFPLFDESFEF---NVPPEQCSVEG--ALLLFTVKDYDL 99

                         90
                 ....*....|.
gi 35493853  352 MGKADFMGRTF 362
Cdd:cd04009  100 LGSNDFEGEAF 110

C2_PKC_alpha_gamma

cd04026

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...

278-359

7.55e-07

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 49.57 E-value: 7.55e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  278 QARSLFAADSSGLSDPFARVFFI-----NQSQCTEVLNETLCPTWDQMLVFDnlelYGEAHELRDdppiIVIEIYDQDSM 352
Cdd:cd04026   21 EAKNLIPMDPNGLSDPYVKLKLIpdpknETKQKTKTIKKTLNPVWNETFTFD----LKPADKDRR----LSIEVWDWDRT 92


                 ....*..
gi 35493853  353 GKADFMG 359
Cdd:cd04026   93 TRNDFMG 99

C2B_Synaptotagmin-4

cd08404

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

806-884

1.05e-06

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: 49.35 E-value: 1.05e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRL--GKTDIRDKENYISK-QLNPVFGKSF--DIEASFPMESMLTVAVYDWDLVGTD 880
Cdd:cd08404   19 VVVLKARHLPKMDVSGLADPYVKVNLyyGKKRISKKKTHVKKcTLNPVFNESFvfDIPSEELEDISVEFLVLDSDRVTKN 98


                 ....
gi 35493853  881 DLIG 884
Cdd:cd08404   99 EVIG 102

C2B_Rabphilin_Doc2

cd08384

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

806-884

2.48e-06

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

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 48.11 E-value: 2.48e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRLgKTDI----RDKENYISKQLNPVFGKSFDIEASFP--MESMLTVAVYDWDLVGT 879
Cdd:cd08384   17 VGIIRCVNLAAMDANGYSDPFVKLYL-KPDAgkksKHKTQVKKKTLNPEFNEEFFYDIKHSdlAKKTLEITVWDKDIGKS 95


                 ....*
gi 35493853  880 DDLIG 884
Cdd:cd08384   96 NDYIG 100

C2B_RasGAP

cd08675

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

804-892

2.55e-06

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 48.14 E-value: 2.55e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPAdINGKADPYIAIRL---GKTDIRdKENYISKQLNPVFGKSFDIEASFPME---------------S 865
Cdd:cd08675    1 LSVRVLECRDLALK-SNGTCDPFARVTLnysSKTDTK-RTKVKKKTNNPRFDEAFYFELTIGFSyekksfkveeedlekS 78

                         90       100
                 ....*....|....*....|....*..
gi 35493853  866 MLTVAVYDWDLVGTDDLIGETKIDLEN 892
Cdd:cd08675   79 ELRVELWHASMVSGDDFLGEVRIPLQG 105

C2B_SLP_1-2-3-4

cd04020

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...

271-359

3.06e-06

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: 48.47 E-value: 3.06e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  271 QLRAHMYQARSLFAADSSGLSDPFARVFFI-----NQSQCTEVLNETLCPTWDQMLVFDNLELygeaHELRDdppiIVIE 345
Cdd:cd04020   28 ELHVWVKEAKNLPALKSGGTSDSFVKCYLLpdkskKSKQKTPVVKKSVNPVWNHTFVYDGVSP----EDLSQ----ACLE 99

                         90
                 ....*....|....*.
gi 35493853  346 --IYDQDSMGKADFMG 359
Cdd:cd04020  100 ltVWDHDKLSSNDFLG 115

C2A_fungal

cd04041

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...

803-890

4.11e-06

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: 46.87 E-value: 4.11e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  803 LVRVYVVRATDLHPADIN-GKADPYIAIRLGKT-DIRDKENYISKQLNPVFGKSF-------DIEASFpmesMLTVAVYD 873
Cdd:cd04041    2 VLVVTIHRATDLPKADFGtGSSDPYVTASFAKFgKPLYSTRIIRKDLNPVWEETWfvlvtpdEVKAGE----RLSCRLWD 77

                         90
                 ....*....|....*..
gi 35493853  874 WDLVGTDDLIGETKIDL 890
Cdd:cd04041   78 SDRFTADDRLGRVEIDL 94

C2B_MCTP_PRT

cd08376

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

279-361

7.10e-06

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 46.48 E-value: 7.10e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  279 ARSLFAADSSGLSDPFARVFFINQSQCTEVLNETLCPTWDQMlvFDnLELYGEAHELRDdppiivIEIYDQDSMGKADFM 358
Cdd:cd08376    9 GKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQ--FD-LHLFDDQSQILE------IEVWDKDTGKKDEFI 79


                 ...
gi 35493853  359 GRT 361
Cdd:cd08376   80 GRC 82

C2B_Synaptotagmin

cd00276

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

806-893

2.14e-05

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: 45.65 E-value: 2.14e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRLGKTD--IRDKENYISKQ-LNPVFGKS--FDIEASFPMESMLTVAVYDWDLVGTD 880
Cdd:cd00276   18 VVVLKARNLPPSDGKGLSDPYVKVSLLQGGkkLKKKKTSVKKGtLNPVFNEAfsFDVPAEQLEEVSLVITVVDKDSVGRN 97

                         90
                 ....*....|...
gi 35493853  881 DLIGETKIDLENR 893
Cdd:cd00276   98 EVIGQVVLGPDSG 110

COG5038

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

796-949

2.58e-05

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 48.99 E-value: 2.58e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  796 SNDPINVlVRVYVVRATDLHPAD--INGKADPYIAIRL-----GKTDIRdkenyiSKQLNPVFGKSFDIeasfPMESM-- 866
Cdd:COG5038  431 SGTAIGV-VEVKIKSAEGLKKSDstINGTVDPYITVTFsdrviGKTRVK------KNTLNPVWNETFYI----LLNSFtd 499

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  867 -LTVAVYDWDLVGTDDLIGETKIDL---------ENRFYSKHRATCGIAQ-TYSTHGYniwrdpmkpSQILTRLCKDGKV 935
Cdd:COG5038  500 pLNLSLYDFNSFKSDKVVGSTQLDLallhqnpvkKNELYEFLRNTKNVGRlTYDLRFF---------PVIEDKKELKGSV 570

                        170
                 ....*....|....
gi 35493853  936 DGPHFGPPGRVKVA 949
Cdd:COG5038  571 EPLEDSNTGILKVT 584

C2_Intersectin

cd08375

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...

804-888

2.61e-05

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 45.45 E-value: 2.61e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPADINGKADPYIAIRLGKTdiRDKENYISKQLNPVFGKSF-----DIEasfpmESMLTVAVYDWDLVG 878
Cdd:cd08375   17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQ--EHKTKVVSDTLNPKWNSSMqffvkDLE-----QDVLCITVFDRDFFS 89

                         90
                 ....*....|
gi 35493853  879 TDDLIGETKI 888
Cdd:cd08375   90 PDDFLGRTEI 99

C2A_Synaptotagmin-like

cd04024

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

272-360

2.75e-05

Pssm-ID: 175990 [Multi-domain] Cd Length: 128 Bit Score: 45.11 E-value: 2.75e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  272 LRAHMYQARSLFAAD--SSGLSDPFARVFFINQSQCTEVLNETLCPTWDqmlVFDNLELYGEAHELRDdppiivIEIYDQ 349
Cdd:cd04024    3 LRVHVVEAKDLAAKDrsGKGKSDPYAILSVGAQRFKTQTIPNTLNPKWN---YWCEFPIFSAQNQLLK------LILWDK 73

                         90
                 ....*....|.
gi 35493853  350 DSMGKADFMGR 360
Cdd:cd04024   74 DRFAGKDYLGE 84

smart00239

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

1067-1170

3.38e-05

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 44.02 E-value: 3.38e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853    1067 SSDIFVRGWLKGQQEDKQDTDVHYHSLtgegNFNWRYLFPFDYLAAEEkiviskkesmfswdeteykipARLTLQIWDAD 1146
Cdd:smart00239   20 KSDPYVKVSLDGDPKEKKKTKVVKNTL----NPVWNETFEFEVPPPEL---------------------AELEIEVYDKD 74

                            90       100
                    ....*....|....*....|....
gi 35493853    1147 HFSADDFLGAIELDLNRFPRGAKT 1170
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLLLGGRH 98

C2_KIAA0528-like

cd08688

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

279-368

3.63e-05

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: 44.22 E-value: 3.63e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  279 ARSLFAAD-SSGLSDPFARVFFINQSQCTEVLNETLCPTW-DQMLVFDNLELygeahELRDDPpiIVIEIYDQDSMGKAD 356
Cdd:cd08688    8 ARDLPVMDrSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVWnSEWFRFEVDDE-----ELQDEP--LQIRVMDHDTYSAND 80

                         90
                 ....*....|....
gi 35493853  357 FMGRTFA--KPLVK 368
Cdd:cd08688   81 AIGKVYIdlNPLLL 94

C2_KIAA0528-like

cd08688

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

804-890

4.36e-05

Pssm-ID: 176070 [Multi-domain] Cd Length: 110 Bit Score: 43.83 E-value: 4.36e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPAD-INGKADPYIAIRLGKTDirDKENYISKQLNPVFGKS---FDIEASFPMESMLTVAVYDWDLVGT 879
Cdd:cd08688    1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFGSTT--YKTDVVKKSLNPVWNSEwfrFEVDDEELQDEPLQIRVMDHDTYSA 78

                         90
                 ....*....|.
gi 35493853  880 DDLIGETKIDL 890
Cdd:cd08688   79 NDAIGKVYIDL 89

C2_fungal_Inn1p-like

cd08681

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...

806-895

5.33e-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: 43.78 E-value: 5.33e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRLGKTDIRDKENYISKQlNPVFgksfDIEASFPMES----MLTVAVYDWDLvGTDD 881
Cdd:cd08681    5 VVVLKARNLPNKRKLDKQDPYCVLRIGGVTKKTKTDFRGGQ-HPEW----DEELRFEITEdkkpILKVAVFDDDK-RKPD 78

                         90
                 ....*....|....
gi 35493853  882 LIGETKIDLENRFY 895
Cdd:cd08681   79 LIGDTEVDLSPALK 92

C2A_Tricalbin-like

cd04044

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

804-891

5.92e-05

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: 44.08 E-value: 5.92e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPAD-INGKADPYIAIRLGKTDIRDKENYISKQLNPVFGKSFDIE-ASFpmESMLTVAVYDWDLVGTDD 881
Cdd:cd04044    4 LAVTIKSARGLKGSDiIGGTVDPYVTFSISNRRELARTKVKKDTSNPVWNETKYILvNSL--TEPLNLTVYDFNDKRKDK 81

                         90
                 ....*....|
gi 35493853  882 LIGETKIDLE 891
Cdd:cd04044   82 LIGTAEFDLS 91

cd00030

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

1066-1173

7.43e-05

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 43.21 E-value: 7.43e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853 1066 KSSDIFVRGWLKGQQedKQDTDVHYHSLtgegNFNWRYLFPFDYLAAEEKIviskkesmfswdeteykiparLTLQIWDA 1145
Cdd:cd00030   18 GKSDPYVKVSLGGKQ--KFKTKVVKNTL----NPVWNETFEFPVLDPESDT---------------------LTVEVWDK 70

                         90       100
                 ....*....|....*....|....*...
gi 35493853 1146 DHFSADDFLGAIELDLNRFPRGAKTAKQ 1173
Cdd:cd00030   71 DRFSKDDFLGEVEIPLSELLDSGKEGEL 98

C2C_Tricalbin-like

cd04045

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

272-376

8.78e-05

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 43.35 E-value: 8.78e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  272 LRAHMYQARSLFAADSSGLSDPFARVFFINQSQC-TEVLNETLCPTWDQMlvfdnleLYGEAHELRDdppIIVIEIYDQD 350
Cdd:cd04045    3 LRLHIRKANDLKNLEGVGKIDPYVRVLVNGIVKGrTVTISNTLNPVWDEV-------LYVPVTSPNQ---KITLEVMDYE 72

                         90       100
                 ....*....|....*....|....*....
gi 35493853  351 SMGKADFMGRT---FAKPLVKMADEAYCP 376
Cdd:cd04045   73 KVGKDRSLGSVeinVSDLIKKNEDGKYVE 101

C2C_Ferlin

cd04018

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

283-381

9.43e-05

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 44.16 E-value: 9.43e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  283 FAADSSGLSDPFARVFFINQSQCTEVLNETLCPTWDQMLVFDnlELYgeahelrddPPI---IVIEIYDQDSMGKADFMG 359
Cdd:cd04018   27 FLGEKKELVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFP--EMF---------PPLcerIKIQIRDWDRVGNDDVIG 95

                         90       100
                 ....*....|....*....|....*
gi 35493853  360 RTFaKPLVKMA---DEAYcPPRFPP 381
Cdd:cd04018   96 THF-IDLSKISnsgDEGF-LPTFGP 118

C2B_Copine

cd04047

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

809-886

1.05e-04

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

Pssm-ID: 176012 [Multi-domain] Cd Length: 110 Bit Score: 42.94 E-value: 1.05e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  809 VRATDLHPADINGKADPYIAIRLGKTDIRD----KENYISKQLNPVFgKSFDIeasfPMESM--------LTVAVYDWDL 876
Cdd:cd04047    7 FSGKKLDKKDFFGKSDPFLEISRQSEDGTWvlvyRTEVIKNTLNPVW-KPFTI----PLQKLcngdydrpIKIEVYDYDS 81

                         90
                 ....*....|
gi 35493853  877 VGTDDLIGET 886
Cdd:cd04047   82 SGKHDLIGEF 91

C2A_MCTP_PRT

cd04042

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

271-377

1.37e-04

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 42.65 E-value: 1.37e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  271 QLRAHMYQARSLFAADSSGLSDPFARvFFINQSQC--TEVLNETLCPTWDQMLVFdnlelygeahELRDDPPIIVIEIYD 348
Cdd:cd04042    1 QLDIHLKEGRNLAARDRGGTSDPYVK-FKYGGKTVykSKTIYKNLNPVWDEKFTL----------PIEDVTQPLYIKVFD 69

                         90       100
                 ....*....|....*....|....*....
gi 35493853  349 QDSMGKADFMGRTFakplVKMADEAYCPP 377
Cdd:cd04042   70 YDRGLTDDFMGSAF----VDLSTLELNKP 94

C2_ArfGAP

cd04038

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...

291-370

1.40e-04

Pssm-ID: 176003 [Multi-domain] Cd Length: 145 Bit Score: 43.47 E-value: 1.40e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  291 SDPFARVFFINQSQCTEVLNETLCPTWDQMLVFdnlelygeahELRDDPPIIVIEIYDQDSMGKADFMGRTFA--KPLVK 368
Cdd:cd04038   22 SDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTL----------SVPNPMAPLKLEVFDKDTFSKDDSMGEAEIdlEPLVE 91


                 ..
gi 35493853  369 MA 370
Cdd:cd04038   92 AA 93

C2A_Ferlin

cd08373

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

808-890

1.85e-04

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

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 42.63 E-value: 1.85e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  808 VVRATDLhpADINGKADPYIAIRLgkTDIRDKENYISKQLNPVFGKSFDieasFPMES------MLTVAVYDWDLVGTDD 881
Cdd:cd08373    2 VVSLKNL--PGLKGKGDRIAKVTF--RGVKKKTRVLENELNPVWNETFE----WPLAGspdpdeSLEIVVKDYEKVGRNR 73


                 ....*....
gi 35493853  882 LIGETKIDL 890
Cdd:cd08373   74 LIGSATVSL 82

C2B_Synaptotagmin

cd00276

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

278-361

2.46e-04

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 42.57 E-value: 2.46e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  278 QARSLFAADSSGLSDPFARVFFINQSQC-----TEVLNETLCPTWDQMLVFDNlelygEAHELRDDppIIVIEIYDQDSM 352
Cdd:cd00276   22 KARNLPPSDGKGLSDPYVKVSLLQGGKKlkkkkTSVKKGTLNPVFNEAFSFDV-----PAEQLEEV--SLVITVVDKDSV 94


                 ....*....
gi 35493853  353 GKADFMGRT 361
Cdd:cd00276   95 GRNEVIGQV 103

pfam00168

C2 domain;

1127-1167

4.37e-04

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 40.77 E-value: 4.37e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 35493853   1127 WDET-EYKIP----ARLTLQIWDADHFSADDFLGAIELDLNRFPRG 1167
Cdd:pfam00168   50 WNETfTFSVPdpenAVLEIEVYDYDRFGRDDFIGEVRIPLSELDSG 95

C2A_Copine

cd04048

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

809-890

4.43e-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: 41.40 E-value: 4.43e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  809 VRATDLHPADINGKADPYIAI-----------RLGKTDIrdkenyISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDL- 876
Cdd:cd04048    7 ISCRNLLDKDVLSKSDPFVVVyvktggsgqwvEIGRTEV------IKNNLNPDFVTTFTVDYYFEEVQKLRFEVYDVDSk 80

                         90
                 ....*....|....*..
gi 35493853  877 ---VGTDDLIGETKIDL 890
Cdd:cd04048   81 skdLSDHDFLGEAECTL 97

C2A_Synaptotagmin-15-17

cd08390

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...

806-892

6.45e-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: 41.09 E-value: 6.45e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGK-ADPYIAIRLGKTDIRDKENYIS-KQLNPVFGKSFDIEASFP--MESMLTVAVYDWDLVGTDD 881
Cdd:cd08390   18 VSLIKARNLPPRTKDVAhCDPFVKVCLLPDERRSLQSKVKrKTQNPNFDETFVFQVSFKelQRRTLRLSVYDVDRFSRHC 97

                         90
                 ....*....|.
gi 35493853  882 LIGETKIDLEN 892
Cdd:cd08390   98 IIGHVLFPLKD 108

C2C_MCTP_PRT_plant

cd04019

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

804-890

1.36e-03

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

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 40.73 E-value: 1.36e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPADINGKADPYIAIRLGKTDIRDKENyISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDLI 883
Cdd:cd04019    2 LRVTVIEAQDLVPSDKNRVPEVFVKAQLGNQVLRTRPS-QTRNGNPSWNEELMFVAAEPFEDHLILSVEDRVGPNKDEPL 80


                 ....*..
gi 35493853  884 GETKIDL 890
Cdd:cd04019   81 GRAVIPL 87

C2C_Ferlin

cd04018

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

824-896

1.39e-03

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 40.69 E-value: 1.39e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  824 DPYIAI----RLGKTDIRdKENYiskqlNPVFGKSFDIEASFPmeSM---LTVAVYDWDLVGTDDLIGETKIDLENRFYS 896
Cdd:cd04018   36 DPYVEVsfagQKVKTSVK-KNSY-----NPEWNEQIVFPEMFP--PLcerIKIQIRDWDRVGNDDVIGTHFIDLSKISNS 107

C2B_Ferlin

cd04011

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

799-890

1.41e-03

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 39.48 E-value: 1.41e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  799 PINVLVRVYVVRATDLHPADIngkaDPYIAIRLG--KTDIRDKEnyisKQLNPVFGKSFDIEASFPMESM----LTVAVY 872
Cdd:cd04011    1 PQDFQVRVRVIEARQLVGGNI----DPVVKVEVGgqKKYTSVKK----GTNCPFYNEYFFFNFHESPDELfdkiIKISVY 72

                         90
                 ....*....|....*...
gi 35493853  873 DWDLVGTDDLIGETKIDL 890
Cdd:cd04011   73 DSRSLRSDTLIGSFKLDV 90

C2A_MCTP_PRT_plant

cd04022

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

279-360

1.71e-03

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

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 40.01 E-value: 1.71e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  279 ARSLFAADSSGLSDPFARVFFINQSQCTEVLNETLCPTWDQMLVFDnlelygeaheLRD--DPPIIVIEIY---DQDSMG 353
Cdd:cd04022    9 AQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFN----------VSDpsRLSNLVLEVYvynDRRSGR 78


                 ....*..
gi 35493853  354 KADFMGR 360
Cdd:cd04022   79 RRSFLGR 85

C2_putative_Elicitor-responsive_gene

cd04049

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

806-894

1.72e-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: 1.72e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  806 VYVVRATDLHPADINGKADPYIAIRLGKtdiRDKENYISKQL--NPVFGKSFDIEASFP---MESMLTVAVYDWDLVGTD 880
Cdd:cd04049    5 VLLISAKGLQDTDFLGKIDPYVIIQCRT---QERKSKVAKGDgrNPEWNEKFKFTVEYPgwgGDTKLILRIMDKDNFSDD 81

                         90
                 ....*....|....
gi 35493853  881 DLIGETKIDLENRF 894
Cdd:cd04049   82 DFIGEATIHLKGLF 95

C2B_Rabphilin_Doc2

cd08384

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

260-359

1.83e-03

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 40.02 E-value: 1.83e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  260 VSLVYTKKQAfQLRAHMYQARSLFAADSSGLSDPFARVFFI-----NQSQCTEVLNETLCPTWDQMLVFDnlelyGEAHE 334
Cdd:cd08384    4 VSLMYNTQRR-GLIVGIIRCVNLAAMDANGYSDPFVKLYLKpdagkKSKHKTQVKKKTLNPEFNEEFFYD-----IKHSD 77

                         90       100
                 ....*....|....*....|....*.
gi 35493853  335 LRDDppIIVIEIYDQDsMGKA-DFMG 359
Cdd:cd08384   78 LAKK--TLEITVWDKD-IGKSnDYIG 100

C2A_fungal

cd04041

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...

1127-1161

1.93e-03

Pssm-ID: 176006 [Multi-domain] Cd Length: 111 Bit Score: 39.17 E-value: 1.93e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 35493853 1127 WDET--------EYKIPARLTLQIWDADHFSADDFLGAIELDL 1161
Cdd:cd04041   52 WEETwfvlvtpdEVKAGERLSCRLWDSDRFTADDRLGRVEIDL 94

C2_Rab11-FIP_classI

cd08682

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...

804-900

1.97e-03

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: 39.74 E-value: 1.97e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPADINGKADPYIAIRLGktdirdKENYIS----KQLNPVfgksFDIEASF---------PMESMLTVA 870
Cdd:cd08682    1 VQVTVLQARGLLCKGKSGTNDAYVIIQLG------KEKYSTsvkeKTTSPV----WKEECSFelpgllsgnGNRATLQLT 70

                         90       100       110
                 ....*....|....*....|....*....|..
gi 35493853  871 VYDWDLVGTDDLIGETKIDLE--NRFYSKHRA 900
Cdd:cd08682   71 VMHRNLLGLDKFLGQVSIPLNdlDEDKGRRRT 102

C2B_Munc13

cd04027

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

804-890

2.16e-03

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

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 39.47 E-value: 2.16e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  804 VRVYVVRATDLHPADINGKADPYIAIRLGKTDIRDKEnyISKQLNPVFGKSFDIEASFPMESmLTVAVYDWD-------- 875
Cdd:cd04027    3 ISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKT--IPQNLNPVWNEKFHFECHNSSDR-IKVRVWDEDddiksrlk 79

                         90
                 ....*....|....*...
gi 35493853  876 ---LVGTDDLIGETKIDL 890
Cdd:cd04027   80 qkfTRESDDFLGQTIIEV 97

C2A_Rasal1_RasA4

cd04054

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...

808-898

2.91e-03

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 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 of these proteins contains 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176018 [Multi-domain] Cd Length: 121 Bit Score: 39.04 E-value: 2.91e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  808 VVRATDLHPADINGKADPYIAIRLGKTDIRdKENYISKQLNPVFGKSFDIEASfPMESMLTVAVYDWDLVGTDDLIGetK 887
Cdd:cd04054    6 IVEGKNLPAKDITGSSDPYCIVKVDNEVII-RTATVWKTLNPFWGEEYTVHLP-PGFHTVSFYVLDEDTLSRDDVIG--K 81

                         90
                 ....*....|.
gi 35493853  888 IDLENRFYSKH 898
Cdd:cd04054   82 VSLTREVISAH 92

C2B_Synaptotagmin-17

cd08410

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...

794-888

3.27e-03

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

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 39.10 E-value: 3.27e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  794 IPSNDPINVlvrvYVVRATDLHPADINGKADPYIAIRL--GKTDIRDKENYISK-QLNPVFGKSFDIEAsfPMESM---- 866
Cdd:cd08410   10 LPSAGRLNV----DIIRAKQLLQTDMSQGSDPFVKIQLvhGLKLIKTKKTSCMRgTIDPFYNESFSFKV--PQEELenvs 83

                         90       100
                 ....*....|....*....|..
gi 35493853  867 LTVAVYDWDLVGTDDLIGETKI 888
Cdd:cd08410   84 LVFTVYGHNVKSSNDFIGRIVI 105

C2_PKC_epsilon

cd04014

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The ...

790-891

3.84e-03

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. 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-II topology.

Pssm-ID: 175981 [Multi-domain] Cd Length: 132 Bit Score: 38.79 E-value: 3.84e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  790 MFQGipsndpinvLVRVYVVRATDLHPAD------INGKA----DPYIAI-----RLGKTDIRdkenyiSKQLNPVFGKS 854
Cdd:cd04014    1 MFTG---------TLKIKICEAVDLKPTDwstrhaVPKKGsqllDPYVSIdvddtHIGKTSTK------PKTNSPVWNEE 65

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 35493853  855 FDIEASFPMesMLTVAVYDWDLVGTDDLIGETKIDLE 891
Cdd:cd04014   66 FTTEVHNGR--NLELTVFHDAAIGPDDFVANCTISFE 100

C2A_Ferlin

cd08373

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

289-359

4.47e-03

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 38.77 E-value: 4.47e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 35493853  289 GLSDPFARVFFINQSQCTEVLNETLCPTWDQMLVFDnleLYGEAhelrDDPPIIVIEIYDQDSMGKADFMG 359
Cdd:cd08373   13 GKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWP---LAGSP----DPDESLEIVVKDYEKVGRNRLIG 76

C2B_Ferlin

cd04011

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

453-530

6.05e-03

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 37.94 E-value: 6.05e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 35493853  453 RDLKRVNLaqvdRPRVDIECAGKGvQSSLIHNYKKNPNFN-TLVkwFEVDLPENELLHPPLNIRVVDCRAFGRYTLVGS 530
Cdd:cd04011   14 RQLVGGNI----DPVVKVEVGGQK-KYTSVKKGTNCPFYNeYFF--FNFHESPDELFDKIIKISVYDSRSLRSDTLIGS 85

C2B_Synaptotagmin-3-5-6-9-10

cd08403

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...

261-359

6.60e-03

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 38.26 E-value: 6.60e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 35493853  261 SLVYTKKqAFQLRAHMYQARSLFAADSSGLSDPFARVFFINQ-----SQCTEVLNETLCPTWDQMLVFDnlelygEAHEL 335
Cdd:cd08403    6 SLCYLPT-AGRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEgrrlkKKKTSVKKNTLNPTYNEALVFD------VPPEN 78

                         90       100
                 ....*....|....*....|....
gi 35493853  336 RDDPPIIvIEIYDQDSMGKADFMG 359
Cdd:cd08403   79 VDNVSLI-IAVVDYDRVGHNELIG 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