NCBI Conserved Domain Search

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

1034-1169

1.74e-41

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: 149.23 E-value: 1.74e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1034 YQLFCYIYQARNLMYNQILTFQEPFIQVVFLNHSLCTQTLRSSAAPTWSQSIIFQHLLLFEDPKDTRENPPLVVLELWQH 1113
Cdd:cd04017      1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720353335 1114 DSRGNKILWGRSMWPPVVWLGLQDWVFTPLRWHPLVReLGEEEGEILASCELILET 1169
Cdd:cd04017     81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYK-GGQSAGELLAAFELIEVT 135

C2B_Ferlin

cd04011

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

164-271

1.52e-38

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: 139.63 E-value: 1.52e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  164 PQHFQVRVKVFEARQLLGNNIKPVVKVNIADQQHLTRIKMGNN-PFFNEIFFQNFHEVPAKFFEENISIEVVDSAASRSK 242
Cdd:cd04011      1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                           90       100
                   ....*....|....*....|....*....
gi 1720353335  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLC 271
Cdd:cd04011     81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLT 109

C2 super family

cl14603

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

5-134

3.38e-21

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 cd08373:

Pssm-ID: 472691 [Multi-domain] Cd Length: 127 Bit Score: 90.78 E-value: 3.38e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335    5 VVESASINPPLSTTPKAFVTVYFRDMMKRTRVEEGHD-PIWNETLIWHLWNQPlENDSFLKVILQDSVSKKKERFIGLAT 83
Cdd:cd08373      1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENELnPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1720353335   84 VPLKRLAqrpKEVMFVRDLILLNHSMKPTNCTVTLHVAQIYDQDTEMTGNE 134
Cdd:cd08373     80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127

FerB

pfam08150

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

691-743

5.42e-21

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

Pssm-ID: 462376 Cd Length: 76 Bit Score: 88.42 E-value: 5.42e-21

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1720353335  691 PQESLPDVLIWLMSRQQRVAYARVPAHTVLFSPAgPLSSGKFCGKIQNILLQY 743
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKY 52

C2 super family

cl14603

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

328-467

7.17e-19

The actual alignment was detected with superfamily member cd04018:

Pssm-ID: 472691 [Multi-domain] Cd Length: 151 Bit Score: 84.99 E-value: 7.17e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  328 FFIYCAEDL-----------HFGTHKSAT----PVLEVELIGDKLRTKPQNPSDNPIWNQILTFQIQLPCLSSYIKFRVM 392
Cdd:cd04018      4 FKIYRAEDLpqmdsgimanvKKAFLGEKKelvdPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIR 83

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720353335  393 DCSKYKCQDEIGSASLCLSQISSTGEEiqgmysGFLPCFGPSFLTLRGgkkPPfrTSEEGTCIMDAVQHGL----AYRG 467
Cdd:cd04018     84 DWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYG---SP--REYSLLDDHQDLNEGLgegvAYRG 151

DysFN super family

cl02740

Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...

743-793

1.02e-06

Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal proteins, dysferlin, myoferlin and hypothetical proteins. Due to an insertion of a dysferlin domain within a second dysferlin domain we have chosen to predict these domains in two parts: the N-terminal region and the C-terminal region.

The actual alignment was detected with superfamily member smart00693:

Pssm-ID: 214777 Cd Length: 62 Bit Score: 47.52 E-value: 1.02e-06

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1720353335   743 YENQAKTRD-DWGQQGLYHCPNFSDVMGRK-ALPKTDFKAPPGWHWKDD-WVVE 793
Cdd:smart00693    9 YENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDDnWSLD 62

FerA super family

cl06973

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

619-649

1.58e-05

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

The actual alignment was detected with superfamily member pfam08165:

Pssm-ID: 462389 Cd Length: 65 Bit Score: 44.11 E-value: 1.58e-05

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1720353335  619 WEKLLKELQEDCRRPLPCMTDQPRANSLDRN 649
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQ 45

FerI super family

cl06959

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...

276-297

4.96e-04

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often located between two C2 domains.

The actual alignment was detected with superfamily member pfam08151:

Pssm-ID: 462377 Cd Length: 52 Bit Score: 39.45 E-value: 4.96e-04

                           10        20
                   ....*....|....*....|..
gi 1720353335  276 TTSGVRGYLKVTICALGVGDQA 297
Cdd:pfam08151    6 ISAGVKGYLKVDISVLGKGDEP 27

Name

Accession

Description

Interval

E-value

C2E_Ferlin

cd04037

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

1444-1567

1.37e-56

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 191.99 E-value: 1.37e-56

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1444 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADDE 1523
Cdd:cd04037      1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1720353335 1524 IGSTVIDLENRLLSGFGARCGLSKSYCKSGPFKWRDQMTPSYLL 1567
Cdd:cd04037     81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124

C2D_Ferlin

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

1034-1169

1.74e-41

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 149.23 E-value: 1.74e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1034 YQLFCYIYQARNLMYNQILTFQEPFIQVVFLNHSLCTQTLRSSAAPTWSQSIIFQHLLLFEDPKDTRENPPLVVLELWQH 1113
Cdd:cd04017      1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720353335 1114 DSRGNKILWGRSMWPPVVWLGLQDWVFTPLRWHPLVReLGEEEGEILASCELILET 1169
Cdd:cd04017     81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYK-GGQSAGELLAAFELIEVT 135

C2B_Ferlin

cd04011

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

164-271

1.52e-38

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 139.63 E-value: 1.52e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  164 PQHFQVRVKVFEARQLLGNNIKPVVKVNIADQQHLTRIKMGNN-PFFNEIFFQNFHEVPAKFFEENISIEVVDSAASRSK 242
Cdd:cd04011      1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                           90       100
                   ....*....|....*....|....*....
gi 1720353335  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLC 271
Cdd:cd04011     81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLT 109

C2A_Ferlin

cd08373

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

5-134

3.38e-21

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: 90.78 E-value: 3.38e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335    5 VVESASINPPLSTTPKAFVTVYFRDMMKRTRVEEGHD-PIWNETLIWHLWNQPlENDSFLKVILQDSVSKKKERFIGLAT 83
Cdd:cd08373      1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENELnPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1720353335   84 VPLKRLAqrpKEVMFVRDLILLNHSMKPTNCTVTLHVAQIYDQDTEMTGNE 134
Cdd:cd08373     80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127

FerB

pfam08150

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

691-743

5.42e-21

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

Pssm-ID: 462376 Cd Length: 76 Bit Score: 88.42 E-value: 5.42e-21

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1720353335  691 PQESLPDVLIWLMSRQQRVAYARVPAHTVLFSPAgPLSSGKFCGKIQNILLQY 743
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKY 52

C2C_Ferlin

cd04018

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

328-467

7.17e-19

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: 84.99 E-value: 7.17e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  328 FFIYCAEDL-----------HFGTHKSAT----PVLEVELIGDKLRTKPQNPSDNPIWNQILTFQIQLPCLSSYIKFRVM 392
Cdd:cd04018      4 FKIYRAEDLpqmdsgimanvKKAFLGEKKelvdPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIR 83

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720353335  393 DCSKYKCQDEIGSASLCLSQISSTGEEiqgmysGFLPCFGPSFLTLRGgkkPPfrTSEEGTCIMDAVQHGL----AYRG 467
Cdd:cd04018     84 DWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYG---SP--REYSLLDDHQDLNEGLgegvAYRG 151

C2 domain;

1443-1537

1.77e-14

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 70.81 E-value: 1.77e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1443 CLVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADD 1522
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80

                           90
                   ....*....|....*
gi 1720353335 1523 EIGSTVIDLENRLLS 1537
Cdd:pfam00168   81 FIGEVRIPLSELDSG 95

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

1444-1538

2.76e-13

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: 67.51 E-value: 2.76e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  1444 LVRVYLIRAINLQPQDYNGLCDPYVILKL-GQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADD 1522
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLdGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                            90
                    ....*....|....*.
gi 1720353335  1523 EIGSTVIDLENRLLSG 1538
Cdd:smart00239   81 FIGQVTIPLSDLLLGG 96

C2 domain;

2-92

2.97e-08

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 53.09 E-value: 2.97e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335    2 LRVVVESAS--INPPLSTTPKAFVTVYFRD--MMKRTRV-EEGHDPIWNETLIWHLwnqPLENDSFLKVILQDSVSKKKE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPYVKVYLLDgkQKKKTKVvKNTLNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*.
gi 1720353335   77 RFIGLATVPLKRLAQR 92
Cdd:pfam00168   80 DFIGEVRIPLSELDSG 95

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

325-413

8.09e-08

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 51.72 E-value: 8.09e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335   325 YLQFFIYCAEDL-HFGTHKSATPVLEVELIGD---KLRTKPQNPSDNPIWNQILTFQIQLPCLSSyIKFRVMDCSKYKCQ 400
Cdd:smart00239    1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAE-LEIEVYDKDRFGRD 79

                            90
                    ....*....|...
gi 1720353335   401 DEIGSASLCLSQI 413
Cdd:smart00239   80 DFIGQVTIPLSDL 92

C2 domain;

325-421

4.35e-07

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 49.62 E-value: 4.35e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  325 YLQFFIYCAEDLH----FGThksATPVLEVELIGD--KLRTKPQNPSDNPIWNQILTFQIQLPcLSSYIKFRVMDCSKYK 398
Cdd:pfam00168    2 RLTVTVIEAKNLPpkdgNGT---SDPYVKVYLLDGkqKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFG 77

                           90       100
                   ....*....|....*....|...
gi 1720353335  399 CQDEIGSASLCLSQISSTGEEIQ 421
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLDG 100

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

2-98

4.76e-07

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 49.79 E-value: 4.76e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335     2 LRVVVESAS--INPPLSTTPKAFVTVYFRDM---MKRTRV-EEGHDPIWNETLIWHLwnqPLENDSFLKVILQDSVSKKK 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLDGDpkeKKKTKVvKNTLNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90       100
                    ....*....|....*....|...
gi 1720353335    76 ERFIGLATVPLKRLAQRPKEVMF 98
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGGRHEKL 101

DysFN

smart00693

Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...

743-793

1.02e-06

Pssm-ID: 214777 Cd Length: 62 Bit Score: 47.52 E-value: 1.02e-06

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1720353335   743 YENQAKTRD-DWGQQGLYHCPNFSDVMGRK-ALPKTDFKAPPGWHWKDD-WVVE 793
Cdd:smart00693    9 YENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDDnWSLD 62

FerA

pfam08165

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

619-649

1.58e-05

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

Pssm-ID: 462389 Cd Length: 65 Bit Score: 44.11 E-value: 1.58e-05

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1720353335  619 WEKLLKELQEDCRRPLPCMTDQPRANSLDRN 649
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQ 45

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

168-264

5.97e-05

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 43.63 E-value: 5.97e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335   168 QVRVKVFEARQLLGNNIK----PVVKVNIADQQHL---TRIKMGN-NPFFNEIFFqnFHEVPakFFEENISIEVVDSAAS 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPKEkkkTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 1720353335   240 RSKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

COG5038

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

1429-1535

5.99e-05

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 48.22 E-value: 5.99e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1429 QFSAWPEIEDFPQMCLVR------VYLIRAINLQPQDYNGLCDPYVILKLGQTKLgsrdsyYPN-----TLDPIFGMMYE 1497
Cdd:COG5038   1020 QVSYTPVPVKLPPVEMVEnsgyltIMLRSGENLPSSDENGYSDPFVKLFLNEKSV------YKTkvvkkTLNPVWNEEFT 1093

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1720353335 1498 LTCNIPLEKDLEIQLFDFDLITADDEIGSTVIDLENRL 1535
Cdd:COG5038   1094 IEVLNRVKDVLTINVNDWDSGEKNDLLGTAEIDLSKLE 1131

C2 domain;

168-270

6.16e-05

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 43.85 E-value: 6.16e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  168 QVRVKVFEARQLLGNNIK----PVVKVNIADQQHL--TRIKMGN-NPFFNEIFFqnFhEVPAkFFEENISIEVVDSAASR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQKkkTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 1720353335  241 SKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104

FerI

pfam08151

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...

276-297

4.96e-04

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often located between two C2 domains.

Pssm-ID: 462377 Cd Length: 52 Bit Score: 39.45 E-value: 4.96e-04

                           10        20
                   ....*....|....*....|..
gi 1720353335  276 TTSGVRGYLKVTICALGVGDQA 297
Cdd:pfam08151    6 ISAGVKGYLKVDISVLGKGDEP 27

C2 domain;

1035-1148

1.29e-03

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 39.99 E-value: 1.29e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1035 QLFCYIYQARNLMYNQILTFQEPFIQVVFL--NHSLCTQTLRSSAAPTWSQSIIFQhllLFEDPKDTrenpplVVLELWQ 1112
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1720353335 1113 HDSRGNKILWGRsmwppvVWLGLQDWVFTPL--RWHPL 1148
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSGEGldGWYPL 104

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

1035-1137

1.48e-03

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 39.78 E-value: 1.48e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  1035 QLFCYIYQARNLMYNQILTFQEPFIQVVFLN---HSLCTQTLRSSAAPTWSQSIIFQhlllfEDPKDTREnpplVVLELW 1111
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFE-----VPPPELAE----LEIEVY 71

                            90       100
                    ....*....|....*....|....*.
gi 1720353335  1112 QHDSRGNKILWGRsmwppvVWLGLQD 1137
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSD 91

Name

Accession

Description

Interval

E-value

C2E_Ferlin

cd04037

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

1444-1567

1.37e-56

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 191.99 E-value: 1.37e-56

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1444 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADDE 1523
Cdd:cd04037      1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1720353335 1524 IGSTVIDLENRLLSGFGARCGLSKSYCKSGPFKWRDQMTPSYLL 1567
Cdd:cd04037     81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124

C2D_Ferlin

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

1034-1169

1.74e-41

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 149.23 E-value: 1.74e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1034 YQLFCYIYQARNLMYNQILTFQEPFIQVVFLNHSLCTQTLRSSAAPTWSQSIIFQHLLLFEDPKDTRENPPLVVLELWQH 1113
Cdd:cd04017      1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720353335 1114 DSRGNKILWGRSMWPPVVWLGLQDWVFTPLRWHPLVReLGEEEGEILASCELILET 1169
Cdd:cd04017     81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYK-GGQSAGELLAAFELIEVT 135

C2B_Ferlin

cd04011

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

164-271

1.52e-38

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 139.63 E-value: 1.52e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  164 PQHFQVRVKVFEARQLLGNNIKPVVKVNIADQQHLTRIKMGNN-PFFNEIFFQNFHEVPAKFFEENISIEVVDSAASRSK 242
Cdd:cd04011      1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                           90       100
                   ....*....|....*....|....*....
gi 1720353335  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLC 271
Cdd:cd04011     81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLT 109

C2A_Ferlin

cd08373

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

5-134

3.38e-21

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 90.78 E-value: 3.38e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335    5 VVESASINPPLSTTPKAFVTVYFRDMMKRTRVEEGHD-PIWNETLIWHLWNQPlENDSFLKVILQDSVSKKKERFIGLAT 83
Cdd:cd08373      1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENELnPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1720353335   84 VPLKRLAqrpKEVMFVRDLILLNHSMKPTNCTVTLHVAQIYDQDTEMTGNE 134
Cdd:cd08373     80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127

FerB

pfam08150

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

691-743

5.42e-21

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

Pssm-ID: 462376 Cd Length: 76 Bit Score: 88.42 E-value: 5.42e-21

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1720353335  691 PQESLPDVLIWLMSRQQRVAYARVPAHTVLFSPAgPLSSGKFCGKIQNILLQY 743
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKY 52

C2C_Ferlin

cd04018

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

328-467

7.17e-19

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 84.99 E-value: 7.17e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  328 FFIYCAEDL-----------HFGTHKSAT----PVLEVELIGDKLRTKPQNPSDNPIWNQILTFQIQLPCLSSYIKFRVM 392
Cdd:cd04018      4 FKIYRAEDLpqmdsgimanvKKAFLGEKKelvdPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIR 83

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720353335  393 DCSKYKCQDEIGSASLCLSQISSTGEEiqgmysGFLPCFGPSFLTLRGgkkPPfrTSEEGTCIMDAVQHGL----AYRG 467
Cdd:cd04018     84 DWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYG---SP--REYSLLDDHQDLNEGLgegvAYRG 151

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

1445-1533

1.66e-15

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 73.64 E-value: 1.66e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1445 VRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGsRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADDEI 1524
Cdd:cd00030      1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKF-KTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDFL 79


                   ....*....
gi 1720353335 1525 GSTVIDLEN 1533
Cdd:cd00030     80 GEVEIPLSE 88

C2 domain;

1443-1537

1.77e-14

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 70.81 E-value: 1.77e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1443 CLVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADD 1522
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80

                           90
                   ....*....|....*
gi 1720353335 1523 EIGSTVIDLENRLLS 1537
Cdd:pfam00168   81 FIGEVRIPLSELDSG 95

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

1444-1538

2.76e-13

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 67.51 E-value: 2.76e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  1444 LVRVYLIRAINLQPQDYNGLCDPYVILKL-GQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADD 1522
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLdGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                            90
                    ....*....|....*.
gi 1720353335  1523 EIGSTVIDLENRLLSG 1538
Cdd:smart00239   81 FIGQVTIPLSDLLLGG 96

C2A_Synaptotagmin-8

cd08387

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

1440-1538

2.58e-10

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: 59.72 E-value: 2.58e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1440 PQMCLVRVYLIRAINLQPQDYNGLCDPYVILKL-------GQTKLGSRdsyypnTLDPIFG--MMYELTCNIPLEKDLEI 1510
Cdd:cd08387     13 KDMGILNVKLIQARNLQPRDFSGTADPYCKVRLlpdrsntKQSKIHKK------TLNPEFDesFVFEVPPQELPKRTLEV 86

                           90       100
                   ....*....|....*....|....*...
gi 1720353335 1511 QLFDFDLITADDEIGSTVIDLENRLLSG 1538
Cdd:cd08387     87 LLYDFDQFSRDECIGVVELPLAEVDLSE 114

C2A_Synaptotagmin-like

cd04024

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

1446-1533

3.32e-09

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: 56.66 E-value: 3.32e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1446 RVYLIRAINLQPQD--YNGLCDPYVILKLGQTKLgsRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADDE 1523
Cdd:cd04024      4 RVHVVEAKDLAAKDrsGKGKSDPYAILSVGAQRF--KTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKDY 81

                           90
                   ....*....|
gi 1720353335 1524 IGSTVIDLEN 1533
Cdd:cd04024     82 LGEFDIALEE 91

C2_ArfGAP

cd04038

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

1444-1532

3.73e-09

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

Pssm-ID: 176003 [Multi-domain] Cd Length: 145 Bit Score: 56.95 E-value: 3.73e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1444 LVRVYLIRAINLQPQDYNGlCDPYVILKLGQTKLGSRDSYypNTLDPIFGMmyELTCNIP-LEKDLEIQLFDFDLITADD 1522
Cdd:cd04038      3 LLKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTRVIK--KNLNPVWNE--ELTLSVPnPMAPLKLEVFDKDTFSKDD 77

                           90
                   ....*....|
gi 1720353335 1523 EIGSTVIDLE 1532
Cdd:cd04038     78 SMGEAEIDLE 87

C2A_RIM1alpha

cd04031

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

1447-1538

5.82e-09

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: 55.72 E-value: 5.82e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1447 VYLIRAINLQPQDYNGLCDPYVILKL--GQTKLGSRDS-YYPNTLDPIFG--MMYEltcNIP----LEKDLEIQLFDFDL 1517
Cdd:cd04031     20 VTVLQARDLPPRDDGSLRNPYVKVYLlpDRSEKSKRRTkTVKKTLNPEWNqtFEYS---NVRretlKERTLEVTVWDYDR 96

                           90       100
                   ....*....|....*....|.
gi 1720353335 1518 ITADDEIGSTVIDLENRLLSG 1538
Cdd:cd04031     97 DGENDFLGEVVIDLADALLDD 117

C2A_C2C_Synaptotagmin_like

cd08391

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

1443-1539

6.21e-09

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: 55.76 E-value: 6.21e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1443 CLVRVYLIRAINLQPQDYN------GLCDPYVILKLGQTKLgsRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFD 1516
Cdd:cd08391      1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRVGAQTF--KSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDED 78

                           90       100
                   ....*....|....*....|...
gi 1720353335 1517 lITADDEIGSTVIDLENRLLSGF 1539
Cdd:cd08391     79 -PDKDDFLGRLSIDLGSVEKKGF 100

C2B_MCTP_PRT

cd08376

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

1444-1533

9.77e-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: 54.95 E-value: 9.77e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1444 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYypNTLDPIFGMMYELtcNIPLEKD--LEIQLFDFDLITAD 1521
Cdd:cd08376      1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCS--KTLNPQWLEQFDL--HLFDDQSqiLEIEVWDKDTGKKD 76

                           90
                   ....*....|..
gi 1720353335 1522 DEIGSTVIDLEN 1533
Cdd:cd08376     77 EFIGRCEIDLSA 88

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

326-420

2.20e-08

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 53.61 E-value: 2.20e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  326 LQFFIYCAEDLH-FGTHKSATPVLEVELIGD-KLRTKPQNPSDNPIWNQILTFQIqLPCLSSYIKFRVMDCSKYKCQDEI 403
Cdd:cd00030      1 LRVTVIEARNLPaKDLNGKSDPYVKVSLGGKqKFKTKVVKNTLNPVWNETFEFPV-LDPESDTLTVEVWDKDRFSKDDFL 79

                           90
                   ....*....|....*..
gi 1720353335  404 GSASLCLSQISSTGEEI 420
Cdd:cd00030     80 GEVEIPLSELLDSGKEG 96

C2 domain;

2-92

2.97e-08

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 53.09 E-value: 2.97e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335    2 LRVVVESAS--INPPLSTTPKAFVTVYFRD--MMKRTRV-EEGHDPIWNETLIWHLwnqPLENDSFLKVILQDSVSKKKE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPYVKVYLLDgkQKKKTKVvKNTLNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*.
gi 1720353335   77 RFIGLATVPLKRLAQR 92
Cdd:pfam00168   80 DFIGEVRIPLSELDSG 95

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

2-102

4.39e-08

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 52.45 E-value: 4.39e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335    2 LRVVVESASINPP--LSTTPKAFVTVYFRDMMK-RTRV-EEGHDPIWNETLIWHLwnqPLENDSFLKVILQDSVSKKKER 77
Cdd:cd00030      1 LRVTVIEARNLPAkdLNGKSDPYVKVSLGGKQKfKTKVvKNTLNPVWNETFEFPV---LDPESDTLTVEVWDKDRFSKDD 77

                           90       100
                   ....*....|....*....|....*
gi 1720353335   78 FIGLATVPLKRLAQRPKEVMFVRDL 102
Cdd:cd00030     78 FLGEVEIPLSELLDSGKEGELWLPL 102

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

325-413

8.09e-08

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 51.72 E-value: 8.09e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335   325 YLQFFIYCAEDL-HFGTHKSATPVLEVELIGD---KLRTKPQNPSDNPIWNQILTFQIQLPCLSSyIKFRVMDCSKYKCQ 400
Cdd:smart00239    1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAE-LEIEVYDKDRFGRD 79

                            90
                    ....*....|...
gi 1720353335   401 DEIGSASLCLSQI 413
Cdd:smart00239   80 DFIGQVTIPLSDL 92

C2D_Tricalbin-like

cd04040

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

1445-1531

1.67e-07

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: 51.41 E-value: 1.67e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1445 VRVYLIRAINLQPQDYNGLCDPYVILKLG-----QTKLGSRdsyypnTLDPIFGmmyElTCNIPL----EKDLEIQLFDF 1515
Cdd:cd04040      1 LTVDVISAENLPSADRNGKSDPFVKFYLNgekvfKTKTIKK------TLNPVWN---E-SFEVPVpsrvRAVLKVEVYDW 70

                           90
                   ....*....|....*.
gi 1720353335 1516 DLITADDEIGSTVIDL 1531
Cdd:cd04040     71 DRGGKDDLLGSAYIDL 86

C2 domain;

325-421

4.35e-07

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 49.62 E-value: 4.35e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  325 YLQFFIYCAEDLH----FGThksATPVLEVELIGD--KLRTKPQNPSDNPIWNQILTFQIQLPcLSSYIKFRVMDCSKYK 398
Cdd:pfam00168    2 RLTVTVIEAKNLPpkdgNGT---SDPYVKVYLLDGkqKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFG 77

                           90       100
                   ....*....|....*....|...
gi 1720353335  399 CQDEIGSASLCLSQISSTGEEIQ 421
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLDG 100

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

2-98

4.76e-07

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 49.79 E-value: 4.76e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335     2 LRVVVESAS--INPPLSTTPKAFVTVYFRDM---MKRTRV-EEGHDPIWNETLIWHLwnqPLENDSFLKVILQDSVSKKK 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLDGDpkeKKKTKVvKNTLNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90       100
                    ....*....|....*....|...
gi 1720353335    76 ERFIGLATVPLKRLAQRPKEVMF 98
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGGRHEKL 101

C2A_MCTP_PRT

cd04042

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

1444-1533

6.76e-07

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: 49.58 E-value: 6.76e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1444 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQtKLGSRDSYYPNTLDPIFgmmYELTCnIPLE---KDLEIQLFDFDLITA 1520
Cdd:cd04042      1 QLDIHLKEGRNLAARDRGGTSDPYVKFKYGG-KTVYKSKTIYKNLNPVW---DEKFT-LPIEdvtQPLYIKVFDYDRGLT 75

                           90
                   ....*....|...
gi 1720353335 1521 DDEIGSTVIDLEN 1533
Cdd:cd04042     76 DDFMGSAFVDLST 88

C2A_Rabphilin_Doc2

cd04035

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

1441-1533

7.26e-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: 49.59 E-value: 7.26e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1441 QMCLvRVYLIRAINLQPQDYNGLCDPYVILKL-----GQTKLgsRDSYYPNTLDPIFG---MMYELTCNIPLEKDLEIQL 1512
Cdd:cd04035     14 NSAL-HCTIIRAKGLKAMDANGLSDPYVKLNLlpgasKATKL--RTKTVHKTRNPEFNetlTYYGITEEDIQRKTLRLLV 90

                           90       100
                   ....*....|....*....|.
gi 1720353335 1513 FDFDLItADDEIGSTVIDLEN 1533
Cdd:cd04035     91 LDEDRF-GNDFLGETRIPLKK 110

DysFN

smart00693

Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...

743-793

1.02e-06

Pssm-ID: 214777 Cd Length: 62 Bit Score: 47.52 E-value: 1.02e-06

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....
gi 1720353335   743 YENQAKTRD-DWGQQGLYHCPNFSDVMGRK-ALPKTDFKAPPGWHWKDD-WVVE 793
Cdd:smart00693    9 YENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDDnWSLD 62

C2_NEDD4_NEDD4L

cd04033

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

1444-1549

1.37e-06

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

Pssm-ID: 175999 [Multi-domain] Cd Length: 133 Bit Score: 49.27 E-value: 1.37e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1444 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQTK-LGSRDSYYPNT----LDPIFGMMYELTCNiPLEKDLEIQLFDFDLI 1518
Cdd:cd04033      1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPDgNGEIDSVQTKTikktLNPKWNEEFFFRVN-PREHRLLFEVFDENRL 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1720353335 1519 TADDEIGSTVIDLENRLLSGFGARCGLS-KSY 1549
Cdd:cd04033     80 TRDDFLGQVEVPLNNLPTETPGNERRYTfKDY 111

C2B_Synaptotagmin-7

cd08405

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

1447-1525

1.57e-06

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

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 49.34 E-value: 1.57e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1447 VYLIRAINLQPQDYNGLCDPYVILKL--GQTKLGSRDS-YYPNTLDPIFGMMYELtcNIPLEK----DLEIQLFDFDLIT 1519
Cdd:cd08405     19 VNIIKARNLKAMDINGTSDPYVKVWLmyKDKRVEKKKTvIKKRTLNPVFNESFIF--NIPLERlretTLIITVMDKDRLS 96


                   ....*.
gi 1720353335 1520 ADDEIG 1525
Cdd:cd08405     97 RNDLIG 102

C2B_Munc13-like

cd04009

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

1446-1533

4.06e-06

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

Pssm-ID: 175976 [Multi-domain] Cd Length: 133 Bit Score: 48.00 E-value: 4.06e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1446 RVYLIRAINLQPQDYNGLCDPYVILKLG-----------QTKLGSrdsyypNTLDPIFGMMYELtcNIPLEKDLE---IQ 1511
Cdd:cd04009     19 RVEILNARNLLPLDSNGSSDPFVKVELLprhlfpdvptpKTQVKK------KTLFPLFDESFEF--NVPPEQCSVegaLL 90

                           90       100
                   ....*....|....*....|....*
gi 1720353335 1512 LF---DFDLITADDEIGSTVIDLEN 1533
Cdd:cd04009     91 LFtvkDYDLLGSNDFEGEAFLPLND 115

C2_E3_ubiquitin_ligase

cd04021

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...

350-413

5.12e-06

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175988 [Multi-domain] Cd Length: 125 Bit Score: 47.27 E-value: 5.12e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720353335  350 VELIGDKL---RTKPQNPSDNPIWNQILTFQIQlPclSSYIKFRVMDCSKYKCQDEIGSASLCLSQI 413
Cdd:cd04021     26 VEVTVDGQppkKTEVSKKTSNPKWNEHFTVLVT-P--QSTLEFKVWSHHTLKADVLLGEASLDLSDI 89

C2B_Rabphilin_Doc2

cd08384

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

1441-1526

1.12e-05

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: 46.57 E-value: 1.12e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1441 QMCLVrVYLIRAINLQPQDYNGLCDPYVILKL---GQTKLGSRDSYYPNTLDPIFG--MMYELTCNIPLEKDLEIQLFDF 1515
Cdd:cd08384     12 RRGLI-VGIIRCVNLAAMDANGYSDPFVKLYLkpdAGKKSKHKTQVKKKTLNPEFNeeFFYDIKHSDLAKKTLEITVWDK 90

                           90
                   ....*....|.
gi 1720353335 1516 DLITADDEIGS 1526
Cdd:cd08384     91 DIGKSNDYIGG 101

FerA

pfam08165

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

619-649

1.58e-05

FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.

Pssm-ID: 462389 Cd Length: 65 Bit Score: 44.11 E-value: 1.58e-05

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1720353335  619 WEKLLKELQEDCRRPLPCMTDQPRANSLDRN 649
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQ 45

C2A_fungal

cd04041

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

1444-1531

2.83e-05

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

Pssm-ID: 176006 [Multi-domain] Cd Length: 111 Bit Score: 44.94 E-value: 2.83e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1444 LVRVYLIRAINLQPQDYN-GLCDPYVILKLGQT-KLGSRDSYYPNTLDPIFgmmyELTC-------NIPLEKDLEIQLFD 1514
Cdd:cd04041      2 VLVVTIHRATDLPKADFGtGSSDPYVTASFAKFgKPLYSTRIIRKDLNPVW----EETWfvlvtpdEVKAGERLSCRLWD 77

                           90
                   ....*....|....*..
gi 1720353335 1515 FDLITADDEIGSTVIDL 1531
Cdd:cd04041     78 SDRFTADDRLGRVEIDL 94

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

169-270

3.29e-05

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 44.37 E-value: 3.29e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  169 VRVKVFEARQLLGNNIK----PVVKVNIADQQHL-TRIKMGN-NPFFNEIFfqNFHEVPAKffEENISIEVVDSAASRSK 242
Cdd:cd00030      1 LRVTVIEARNLPAKDLNgksdPYVKVSLGGKQKFkTKVVKNTlNPVWNETF--EFPVLDPE--SDTLTVEVWDKDRFSKD 76

                           90       100
                   ....*....|....*....|....*...
gi 1720353335  243 AEIGRFQTDIGFIYHSPGHTllRKWLGL 270
Cdd:cd00030     77 DFLGEVEIPLSELLDSGKEG--ELWLPL 102

C2_PKC_alpha_gamma

cd04026

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

1447-1526

4.68e-05

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: 44.95 E-value: 4.68e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1447 VYLIRAINLQPQDYNGLCDPYVILKL-----GQTKLGSRDsyYPNTLDPIFGM--MYELTCNiPLEKDLEIQLFDFDLIT 1519
Cdd:cd04026     17 VEVREAKNLIPMDPNGLSDPYVKLKLipdpkNETKQKTKT--IKKTLNPVWNEtfTFDLKPA-DKDRRLSIEVWDWDRTT 93


                   ....*..
gi 1720353335 1520 ADDEIGS 1526
Cdd:cd04026     94 RNDFMGS 100

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

168-264

5.97e-05

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 43.63 E-value: 5.97e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335   168 QVRVKVFEARQLLGNNIK----PVVKVNIADQQHL---TRIKMGN-NPFFNEIFFqnFHEVPakFFEENISIEVVDSAAS 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPKEkkkTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 1720353335   240 RSKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

COG5038

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

1429-1535

5.99e-05

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 48.22 E-value: 5.99e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1429 QFSAWPEIEDFPQMCLVR------VYLIRAINLQPQDYNGLCDPYVILKLGQTKLgsrdsyYPN-----TLDPIFGMMYE 1497
Cdd:COG5038   1020 QVSYTPVPVKLPPVEMVEnsgyltIMLRSGENLPSSDENGYSDPFVKLFLNEKSV------YKTkvvkkTLNPVWNEEFT 1093

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1720353335 1498 LTCNIPLEKDLEIQLFDFDLITADDEIGSTVIDLENRL 1535
Cdd:COG5038   1094 IEVLNRVKDVLTINVNDWDSGEKNDLLGTAEIDLSKLE 1131

C2 domain;

168-270

6.16e-05

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 43.85 E-value: 6.16e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  168 QVRVKVFEARQLLGNNIK----PVVKVNIADQQHL--TRIKMGN-NPFFNEIFFqnFhEVPAkFFEENISIEVVDSAASR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQKkkTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 1720353335  241 SKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104

C2_PLC_like

cd00275

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

346-413

8.11e-05

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 44.07 E-value: 8.11e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720353335  346 PVLEVELIGD------KLRTKP-QNPSDNPIWNQILTFQIQLPCLsSYIKFRVMDCSKyKCQDEIGSASLCLSQI 413
Cdd:cd00275     27 PYVEVEIHGLpaddsaKFKTKVvKNNGFNPVWNETFEFDVTVPEL-AFLRFVVYDEDS-GDDDFLGQACLPLDSL 99

C2_ArfGAP

cd04038

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

342-442

1.18e-04

Pssm-ID: 176003 [Multi-domain] Cd Length: 145 Bit Score: 43.85 E-value: 1.18e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  342 KSATPVLEVELIGDKLRTKPQNPSDNPIWNQILTFQIQLPCLSsyIKFRVMDCSKYKCQDEIGSASLCLS---------- 411
Cdd:cd04038     20 TSSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP--LKLEVFDKDTFSKDDSMGEAEIDLEplveaakldh 97

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1720353335  412 -QISSTGEEIQGMYSGFLPCFG-PSFLTLRGGK 442
Cdd:cd04038     98 lRDTPGGTQIKKVLPSVENCLAsESHITWKDGK 130

C2C_Tricalbin-like

cd04045

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

1445-1533

1.88e-04

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: 42.58 E-value: 1.88e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1445 VRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGsRDSYYPNTLDPIFGMMYELTCNIPLEKDLeIQLFDFDLITADDEI 1524
Cdd:cd04045      3 LRLHIRKANDLKNLEGVGKIDPYVRVLVNGIVKG-RTVTISNTLNPVWDEVLYVPVTSPNQKIT-LEVMDYEKVGKDRSL 80


                   ....*....
gi 1720353335 1525 GSTVIDLEN 1533
Cdd:cd04045     81 GSVEINVSD 89

C2A_Synaptotagmin-1-5-6-9-10

cd08385

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

1438-1531

2.27e-04

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

Pssm-ID: 176031 [Multi-domain] Cd Length: 124 Bit Score: 42.64 E-value: 2.27e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1438 DFPQMCLVrVYLIRAINLQPQDYNGLCDPYVIL-------KLGQTKLgsrdsyYPNTLDPIFGMMYelTCNIPL----EK 1506
Cdd:cd08385     12 DFQSNQLT-VGIIQAADLPAMDMGGTSDPYVKVyllpdkkKKFETKV------HRKTLNPVFNETF--TFKVPYselgNK 82

                           90       100
                   ....*....|....*....|....*
gi 1720353335 1507 DLEIQLFDFDLITADDEIGSTVIDL 1531
Cdd:cd08385     83 TLVFSVYDFDRFSKHDLIGEVRVPL 107

C2_Ras_p21A1

cd08400

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

2-89

2.45e-04

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

Pssm-ID: 176045 [Multi-domain] Cd Length: 126 Bit Score: 42.74 E-value: 2.45e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335    2 LRVVVESASiNPPLSTTPKAFVTVYFRDM-MKRTRVEEGHDPIWNETLIwhLWNQPLENDSFlKVILQDSVSKKKERFIG 80
Cdd:cd08400      6 LQLNVLEAH-KLPVKHVPHPYCVISLNEVkVARTKVREGPNPVWSEEFV--FDDLPPDVNSF-TISLSNKAKRSKDSEIA 81


                   ....*....
gi 1720353335   81 LATVPLKRL 89
Cdd:cd08400     82 EVTVQLSKL 90

FerI

pfam08151

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...

276-297

4.96e-04

FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often located between two C2 domains.

Pssm-ID: 462377 Cd Length: 52 Bit Score: 39.45 E-value: 4.96e-04

                           10        20
                   ....*....|....*....|..
gi 1720353335  276 TTSGVRGYLKVTICALGVGDQA 297
Cdd:pfam08151    6 ISAGVKGYLKVDISVLGKGDEP 27

C2D_Tricalbin-like

cd04040

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

346-413

9.33e-04

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 40.63 E-value: 9.33e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  346 PVLEVELIGDKL-RTKPQNPSDNPIWNQilTFQIQLPCLS-SYIKFRVMDCSKYKCQDEIGSASLCLSQI 413
Cdd:cd04040     22 PFVKFYLNGEKVfKTKTIKKTLNPVWNE--SFEVPVPSRVrAVLKVEVYDWDRGGKDDLLGSAYIDLSDL 89

C2D_Ferlin

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

1446-1529

1.01e-03

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 40.99 E-value: 1.01e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1446 RVYLIRAINLQPQDYNGLCDPYV-ILKLGQTKlgsRDSYYPNTLDP------------IFGMMYELTCNIPLekdLEIQL 1512
Cdd:cd04017      4 RAYIYQARDLLAADKSGLSDPFArVSFLNQSQ---ETEVIKETLSPtwdqtlifdeveLYGSPEEIAQNPPL---VVVEL 77

                           90
                   ....*....|....*..
gi 1720353335 1513 FDFDLITADDEIGSTVI 1529
Cdd:cd04017     78 FDQDSVGKDEFLGRSVA 94

C2C_MCTP_PRT

cd08377

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

1447-1531

1.02e-03

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

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 40.75 E-value: 1.02e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1447 VYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYypNTLDPIFGMMYelTCNIpleKD----LEIQLFDFDLITADD 1522
Cdd:cd08377      5 VKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIY--KTLNPEWNKIF--TFPI---KDihdvLEVTVYDEDKDKKPE 77


                   ....*....
gi 1720353335 1523 EIGSTVIDL 1531
Cdd:cd08377     78 FLGKVAIPL 86

C2_putative_Elicitor-responsive_gene

cd04049

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

366-419

1.27e-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: 40.39 E-value: 1.27e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720353335  366 DNPIWNQILTFQIQLPCLS--SYIKFRVMDCSKYKCQDEIGSASLCLSQISSTGEE 419
Cdd:cd04049     45 RNPEWNEKFKFTVEYPGWGgdTKLILRIMDKDNFSDDDFIGEATIHLKGLFEEGVE 100

C2 domain;

1035-1148

1.29e-03

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 39.99 E-value: 1.29e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1035 QLFCYIYQARNLMYNQILTFQEPFIQVVFL--NHSLCTQTLRSSAAPTWSQSIIFQhllLFEDPKDTrenpplVVLELWQ 1112
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1720353335 1113 HDSRGNKILWGRsmwppvVWLGLQDWVFTPL--RWHPL 1148
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSGEGldGWYPL 104

C2C_Ferlin

cd04018

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

1040-1088

1.41e-03

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 41.08 E-value: 1.41e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720353335 1040 IYQARNL-------MYNQILTFQ-------EPFIQVVFLNHSLCTQTLRSSAAPTWSQSIIFQ 1088
Cdd:cd04018      6 IYRAEDLpqmdsgiMANVKKAFLgekkelvDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFP 68

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

1035-1137

1.48e-03

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 39.78 E-value: 1.48e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  1035 QLFCYIYQARNLMYNQILTFQEPFIQVVFLN---HSLCTQTLRSSAAPTWSQSIIFQhlllfEDPKDTREnpplVVLELW 1111
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFE-----VPPPELAE----LEIEVY 71

                            90       100
                    ....*....|....*....|....*.
gi 1720353335  1112 QHDSRGNKILWGRsmwppvVWLGLQD 1137
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSD 91

C2A_Tricalbin-like

cd04044

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

1445-1532

1.62e-03

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: 40.23 E-value: 1.62e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1445 VRVYLIRAINLQPQDY-NGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNiPLEKDLEIQLFDFDLITADDE 1523
Cdd:cd04044      4 LAVTIKSARGLKGSDIiGGTVDPYVTFSISNRRELARTKVKKDTSNPVWNETKYILVN-SLTEPLNLTVYDFNDKRKDKL 82


                   ....*....
gi 1720353335 1524 IGSTVIDLE 1532
Cdd:cd04044     83 IGTAEFDLS 91

C2A_Synaptotagmin-15-17

cd08390

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

1447-1538

1.66e-03

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

Pssm-ID: 176036 [Multi-domain] Cd Length: 123 Bit Score: 39.93 E-value: 1.66e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1447 VYLIRAINLQPQDYN-GLCDPYVILKLGQTKLGSRDSYY-PNTLDPIFGMMYELtcNIP----LEKDLEIQLFDFDLITA 1520
Cdd:cd08390     18 VSLIKARNLPPRTKDvAHCDPFVKVCLLPDERRSLQSKVkRKTQNPNFDETFVF--QVSfkelQRRTLRLSVYDVDRFSR 95

                           90
                   ....*....|....*...
gi 1720353335 1521 DDEIGSTVIDLENRLLSG 1538
Cdd:cd08390     96 HCIIGHVLFPLKDLDLVK 113

C2_putative_Elicitor-responsive_gene

cd04049

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

1447-1538

2.27e-03

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 39.62 E-value: 2.27e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1447 VYLIRAINLQPQDYNGLCDPYVILKLG----QTKLGSRDSYYP--------NTLDPIFGMMYELTCNIplekdleiqlFD 1514
Cdd:cd04049      5 VLLISAKGLQDTDFLGKIDPYVIIQCRtqerKSKVAKGDGRNPewnekfkfTVEYPGWGGDTKLILRI----------MD 74

                           90       100
                   ....*....|....*....|....
gi 1720353335 1515 FDLITADDEIGSTVIDLENRLLSG 1538
Cdd:cd04049     75 KDNFSDDDFIGEATIHLKGLFEEG 98

C2B_Synaptotagmin

cd00276

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

1447-1534

2.58e-03

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: 39.87 E-value: 2.58e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1447 VYLIRAINLQPQDYNGLCDPYV---ILKLGQtKLGSRD-SYYPNTLDPIFG--MMYELTCNIPLEKDLEIQLFDFDLITA 1520
Cdd:cd00276     18 VVVLKARNLPPSDGKGLSDPYVkvsLLQGGK-KLKKKKtSVKKGTLNPVFNeaFSFDVPAEQLEEVSLVITVVDKDSVGR 96

                           90
                   ....*....|....
gi 1720353335 1521 DDEIGSTVIDLENR 1534
Cdd:cd00276     97 NEVIGQVVLGPDSG 110

C2_Calpain

cd04046

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...

1440-1492

2.91e-03

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. 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: 176011 [Multi-domain] Cd Length: 126 Bit Score: 39.57 E-value: 2.91e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1720353335 1440 PQmCLVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYypNTLDPIF 1492
Cdd:cd04046      1 PQ-VVTQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQK--DTLSPEF 50

C2B_Synaptotagmin-like

cd04050

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

1-97

3.20e-03

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

Pssm-ID: 176015 [Multi-domain] Cd Length: 105 Bit Score: 38.70 E-value: 3.20e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335    1 MLRVVVESASiNPPL---STTPKAFVTVYFRDMMKRTRVEEG-HDPIWNET---LIWHLWNQPLEndsfLKVIlqdsvSK 73
Cdd:cd04050      1 LLFVYLDSAK-NLPLaksTKEPSPYVELTVGKTTQKSKVKERtNNPVWEEGftfLVRNPENQELE----IEVK-----DD 70

                           90       100
                   ....*....|....*....|....
gi 1720353335   74 KKERFIGLATVPLKRLAQRPKEVM 97
Cdd:cd04050     71 KTGKSLGSLTLPLSELLKEPDLTL 94

C2_PLC_like

cd00275

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

22-91

3.42e-03

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 39.45 E-value: 3.42e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720353335   22 FVTVYFRDM------MKRTRV--EEGHDPIWNETLIWHLWNQPLendSFLKVILQDSVSKKKErFIGLATVPLKRLAQ 91
Cdd:cd00275     28 YVEVEIHGLpaddsaKFKTKVvkNNGFNPVWNETFEFDVTVPEL---AFLRFVVYDEDSGDDD-FLGQACLPLDSLRQ 101

C2A_Ferlin

cd08373

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

339-418

4.79e-03

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 38.77 E-value: 4.79e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335  339 GTHKSATPVLEVELIGDKLRTKPQNPSDNPIWNQILTFQIQLPCL-SSYIKFRVMDCSKYKCQDEIGSASLCLSQISSTG 417
Cdd:cd08373     10 GLKGKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGSPDpDESLEIVVKDYEKVGRNRLIGSATVSLQDLVSEG 89


                   .
gi 1720353335  418 E 418
Cdd:cd08373     90 L 90

C2B_Synaptotagmin-1

cd08402

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

1447-1529

6.90e-03

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

Pssm-ID: 176047 [Multi-domain] Cd Length: 136 Bit Score: 38.54 E-value: 6.90e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1447 VYLIRAINLQPQDYNGLCDPYVILKLGQ-TKLGSRD--SYYPNTLDPIFGMMYelTCNIPLEK----DLEIQLFDFDLIT 1519
Cdd:cd08402     19 VVILEAKNLKKMDVGGLSDPYVKIHLMQnGKRLKKKktTIKKRTLNPYYNESF--SFEVPFEQiqkvHLIVTVLDYDRIG 96

                           90
                   ....*....|
gi 1720353335 1520 ADDEIGSTVI 1529
Cdd:cd08402     97 KNDPIGKVVL 106

C2B_Synaptotagmin-4

cd08404

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

1447-1529

8.36e-03

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

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 38.56 E-value: 8.36e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720353335 1447 VYLIRAINLQPQDYNGLCDPYVILKL--GQTKLGSRDSYYPN-TLDPIFG--MMYELTCNIPLEKDLEIQLFDFDLITAD 1521
Cdd:cd08404     19 VVVLKARHLPKMDVSGLADPYVKVNLyyGKKRISKKKTHVKKcTLNPVFNesFVFDIPSEELEDISVEFLVLDSDRVTKN 98


                   ....*...
gi 1720353335 1522 DEIGSTVI 1529
Cdd:cd08404     99 EVIGRLVL 106