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Conserved domains on  [gi|767920460|ref|XP_011510430|]
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fer-1-like protein 5 isoform X17 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1076-1211 2.29e-57

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: 194.30  E-value: 2.29e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460 1076 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1155
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 767920460 1156 DFWGKESLWGRSVWPPMVWLDLQDRILPPMRWHPLVKElGKEEGEILASCELILQT 1211
Cdd:cd04017    81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 164-273 1.25e-42

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: 151.19  E-value: 1.25e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  164 PQHFQVRVKVFEARQLMGNNIKPVVKVSIAGQQHQTRIKMGNN-PFFNEIFFQNFHEVPAKFFDETILIQVVNSSAMRYK 242
Cdd:cd04011     1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 767920460  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLCQP 273
Cdd:cd04011    81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLTDP 111
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 5-134 1.14e-38

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: 140.47  E-value: 1.14e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460    5 VVQSAKIDPPLAPLPRPCMSIDFRDIKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDMGSQKKERFIGLAT 83
Cdd:cd08373     1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767920460   84 VLLKPLLkqpSEVLFVKDLTLLNHSMKPTDCTVTLQVAHMSNQDIEKTGAE 134
Cdd:cd08373    80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127
FerB pfam08150
FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.
 692-765 2.39e-28

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


:

Pssm-ID: 462376  Cd Length: 76  Bit Score: 108.84  E-value: 2.39e-28
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767920460   692 PQMGLPDVMIWLVAKEQRVAYAQVPAHSVLFSPAgALHSGRLCGKIQTLFLQYPEGEGQKD---VLPAHLRVCMWLG 765
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKYPGKKAKGPagwEIPAKLRVYLWLG 76
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 331-468 8.33e-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 cd04018:

Pssm-ID: 472691 [Multi-domain]  Cd Length: 151  Bit Score: 90.38  E-value: 8.33e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  331 IYCAEDL----------HLKKHQS-----VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSSYIKFRVLDC 395
Cdd:cd04018     6 IYRAEDLpqmdsgimanVKKAFLGekkelVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIRDW 85

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767920460  396 RKKDCPDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGGKKApFRIQEEGACIPDSVRDGLAYRG 468
Cdd:cd04018    86 DRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGSPRE-YSLLDDHQDLNEGLGEGVAYRG 151
DysFN smart00693
Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...
 780-838 2.42e-08

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.


:

Pssm-ID: 214777  Cd Length: 62  Bit Score: 51.76  E-value: 2.42e-08
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767920460    780 DTAVYAEMYENQAKYKD-QWGQQGLYHCPNFSDVMGNK-TLPMTDFQPPLGWHWQD-SWTVE 838
Cdd:smart00693    1 PIRFTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDdNWSLD 62
FerA super family cl06973
FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.
 620-670 6.92e-07

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: 47.58  E-value: 6.92e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 767920460   620 WEKLLRELAEDCKRPLPCMTYQPKATSLDRKRWQLRSLLLQELAQKAKQAK 670
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALKLR 65
FerI super family cl06959
FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...
 273-312 5.14e-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: 39.07  E-value: 5.14e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 767920460   273 PNNPGSGVTGYLKVTIYALGVGDQALIDQKLLYGTDDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42
 
Name Accession Description Interval E-value
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1076-1211 2.29e-57

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: 194.30  E-value: 2.29e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460 1076 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1155
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 767920460 1156 DFWGKESLWGRSVWPPMVWLDLQDRILPPMRWHPLVKElGKEEGEILASCELILQT 1211
Cdd:cd04017    81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 164-273 1.25e-42

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: 151.19  E-value: 1.25e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  164 PQHFQVRVKVFEARQLMGNNIKPVVKVSIAGQQHQTRIKMGNN-PFFNEIFFQNFHEVPAKFFDETILIQVVNSSAMRYK 242
Cdd:cd04011     1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 767920460  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLCQP 273
Cdd:cd04011    81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLTDP 111
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 5-134 1.14e-38

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: 140.47  E-value: 1.14e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460    5 VVQSAKIDPPLAPLPRPCMSIDFRDIKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDMGSQKKERFIGLAT 83
Cdd:cd08373     1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767920460   84 VLLKPLLkqpSEVLFVKDLTLLNHSMKPTDCTVTLQVAHMSNQDIEKTGAE 134
Cdd:cd08373    80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127
FerB pfam08150
FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.
 692-765 2.39e-28

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


Pssm-ID: 462376  Cd Length: 76  Bit Score: 108.84  E-value: 2.39e-28
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767920460   692 PQMGLPDVMIWLVAKEQRVAYAQVPAHSVLFSPAgALHSGRLCGKIQTLFLQYPEGEGQKD---VLPAHLRVCMWLG 765
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKYPGKKAKGPagwEIPAKLRVYLWLG 76
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 331-468 8.33e-21

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: 90.38  E-value: 8.33e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  331 IYCAEDL----------HLKKHQS-----VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSSYIKFRVLDC 395
Cdd:cd04018     6 IYRAEDLpqmdsgimanVKKAFLGekkelVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIRDW 85

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767920460  396 RKKDCPDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGGKKApFRIQEEGACIPDSVRDGLAYRG 468
Cdd:cd04018    86 DRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGSPRE-YSLLDDHQDLNEGLGEGVAYRG 151
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 326-414 8.52e-12

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: 62.89  E-value: 8.52e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460    326 YLQLFIYCAEDL-HLKKHQSVNPQLEVELIG---EKLRTHMQTQTDNPIWNQILTFRIQLPCLSSyIKFRVLDCRKKDCP 401
Cdd:smart00239    1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFEVPPPELAE-LEIEVYDKDRFGRD 79

                            90
                    ....*....|...
gi 767920460    402 DEIGTASLSLNQI 414
Cdd:smart00239   80 DFIGQVTIPLSDL 92
C2 pfam00168
C2 domain;
326-426 2.87e-10

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 58.48  E-value: 2.87e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460   326 YLQLFIYCAEDLHLK-KHQSVNPQLEVELIG--EKLRTHMQTQTDNPIWNQILTFRIQLPcLSSYIKFRVLDCRKKDCPD 402
Cdd:pfam00168    2 RLTVTVIEAKNLPPKdGNGTSDPYVKVYLLDgkQKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFGRDD 80

                           90       100
                   ....*....|....*....|....
gi 767920460   403 EIGTASLSLNQISStGEEIEGVYS 426
Cdd:pfam00168   81 FIGEVRIPLSELDS-GEGLDGWYP 103
DysFN smart00693
Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...
 780-838 2.42e-08

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.


Pssm-ID: 214777  Cd Length: 62  Bit Score: 51.76  E-value: 2.42e-08
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767920460    780 DTAVYAEMYENQAKYKD-QWGQQGLYHCPNFSDVMGNK-TLPMTDFQPPLGWHWQD-SWTVE 838
Cdd:smart00693    1 PIRFTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDdNWSLD 62
C2 pfam00168
C2 domain;
2-92 3.46e-07

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 49.62  E-value: 3.46e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460     2 LRLVVQSAK--IDPPLAPLPRP--CMSIDFRDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKKE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPyvKVYLLDGKQKKKTKVVKNTlNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*.
gi 767920460    77 RFIGLATVLLKPLLKQ 92
Cdd:pfam00168   80 DFIGEVRIPLSELDSG 95
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 2-93 4.34e-07

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: 49.41  E-value: 4.34e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460      2 LRLVVQSAK--IDPPLAPLPRPCMSIDF---RDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKK 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLdgdPKEKKKTKVVKNTlNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90
                    ....*....|....*...
gi 767920460     76 ERFIGLATVLLKPLLKQP 93
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGG 96
FerA pfam08165
FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.
 620-670 6.92e-07

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


Pssm-ID: 462389  Cd Length: 65  Bit Score: 47.58  E-value: 6.92e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 767920460   620 WEKLLRELAEDCKRPLPCMTYQPKATSLDRKRWQLRSLLLQELAQKAKQAK 670
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALKLR 65
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 168-264 1.89e-06

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: 47.48  E-value: 1.89e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460    168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQ---HQTRIKMGN-NPFFNEIFFqnFHEVPakFFDETILIQVVNSSAM 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPkekKKTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 767920460    240 RYKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
168-270 9.73e-06

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 45.77  E-value: 9.73e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460   168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQH--QTRIKMGN-NPFFNEIFFqnFhEVPAkFFDETILIQVVNSSAMR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQkkKTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 767920460   241 YKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104
C2 pfam00168
C2 domain;
1077-1190 1.39e-05

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 45.00  E-value: 1.39e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  1077 QLFCYIYQARNLVSNQILTFQGPFIRVVFL--NHSQCTQTLRSSAGPTWAQTLIFQhllLYENPQDTkespplVVLELWQ 1154
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 767920460  1155 RDFWGKESLWGRsvwppmVWLDLQDRIL--PPMRWHPL 1190
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSgeGLDGWYPL 104
FerI pfam08151
FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...
 273-312 5.14e-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: 39.07  E-value: 5.14e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 767920460   273 PNNPGSGVTGYLKVTIYALGVGDQALIDQKLLYGTDDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1077-1188 1.67e-03

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: 39.01  E-value: 1.67e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460   1077 QLFCYIYQARNLVSNQILTFQGPFIRVVFLN---HSQCTQTLRSSAGPTWAQTLIFqhlllYENPQDTKEspplVVLELW 1153
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEF-----EVPPPELAE----LEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 767920460   1154 QRDFWGKESLWGRsvwppmVWLDLQDRILPPMRWH 1188
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSDLLLGGRHEK 100
 
Name Accession Description Interval E-value
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1076-1211 2.29e-57

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: 194.30  E-value: 2.29e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460 1076 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1155
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 767920460 1156 DFWGKESLWGRSVWPPMVWLDLQDRILPPMRWHPLVKElGKEEGEILASCELILQT 1211
Cdd:cd04017    81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 164-273 1.25e-42

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: 151.19  E-value: 1.25e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  164 PQHFQVRVKVFEARQLMGNNIKPVVKVSIAGQQHQTRIKMGNN-PFFNEIFFQNFHEVPAKFFDETILIQVVNSSAMRYK 242
Cdd:cd04011     1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 767920460  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLCQP 273
Cdd:cd04011    81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLTDP 111
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 5-134 1.14e-38

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: 140.47  E-value: 1.14e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460    5 VVQSAKIDPPLAPLPRPCMSIDFRDIKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDMGSQKKERFIGLAT 83
Cdd:cd08373     1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767920460   84 VLLKPLLkqpSEVLFVKDLTLLNHSMKPTDCTVTLQVAHMSNQDIEKTGAE 134
Cdd:cd08373    80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127
FerB pfam08150
FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.
 692-765 2.39e-28

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


Pssm-ID: 462376  Cd Length: 76  Bit Score: 108.84  E-value: 2.39e-28
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767920460   692 PQMGLPDVMIWLVAKEQRVAYAQVPAHSVLFSPAgALHSGRLCGKIQTLFLQYPEGEGQKD---VLPAHLRVCMWLG 765
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKYPGKKAKGPagwEIPAKLRVYLWLG 76
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 331-468 8.33e-21

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: 90.38  E-value: 8.33e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  331 IYCAEDL----------HLKKHQS-----VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSSYIKFRVLDC 395
Cdd:cd04018     6 IYRAEDLpqmdsgimanVKKAFLGekkelVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIRDW 85

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767920460  396 RKKDCPDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGGKKApFRIQEEGACIPDSVRDGLAYRG 468
Cdd:cd04018    86 DRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGSPRE-YSLLDDHQDLNEGLGEGVAYRG 151
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 326-414 8.52e-12

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: 62.89  E-value: 8.52e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460    326 YLQLFIYCAEDL-HLKKHQSVNPQLEVELIG---EKLRTHMQTQTDNPIWNQILTFRIQLPCLSSyIKFRVLDCRKKDCP 401
Cdd:smart00239    1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFEVPPPELAE-LEIEVYDKDRFGRD 79

                            90
                    ....*....|...
gi 767920460    402 DEIGTASLSLNQI 414
Cdd:smart00239   80 DFIGQVTIPLSDL 92
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 327-426 1.78e-10

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 59.00  E-value: 1.78e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  327 LQLFIYCAEDLHLK-KHQSVNPQLEVELIGE-KLRTHMQTQTDNPIWNQILTFRIqLPCLSSYIKFRVLDCRKKDCPDEI 404
Cdd:cd00030     1 LRVTVIEARNLPAKdLNGKSDPYVKVSLGGKqKFKTKVVKNTLNPVWNETFEFPV-LDPESDTLTVEVWDKDRFSKDDFL 79

                          90       100
                  ....*....|....*....|..
gi 767920460  405 GTASLSLNQISSTGEEIEGVYS 426
Cdd:cd00030    80 GEVEIPLSELLDSGKEGELWLP 101
C2 pfam00168
C2 domain;
326-426 2.87e-10

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 58.48  E-value: 2.87e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460   326 YLQLFIYCAEDLHLK-KHQSVNPQLEVELIG--EKLRTHMQTQTDNPIWNQILTFRIQLPcLSSYIKFRVLDCRKKDCPD 402
Cdd:pfam00168    2 RLTVTVIEAKNLPPKdGNGTSDPYVKVYLLDgkQKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFGRDD 80

                           90       100
                   ....*....|....*....|....
gi 767920460   403 EIGTASLSLNQISStGEEIEGVYS 426
Cdd:pfam00168   81 FIGEVRIPLSELDS-GEGLDGWYP 103
DysFN smart00693
Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...
 780-838 2.42e-08

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.


Pssm-ID: 214777  Cd Length: 62  Bit Score: 51.76  E-value: 2.42e-08
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767920460    780 DTAVYAEMYENQAKYKD-QWGQQGLYHCPNFSDVMGNK-TLPMTDFQPPLGWHWQD-SWTVE 838
Cdd:smart00693    1 PIRFTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDdNWSLD 62
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 331-423 1.26e-07

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: 51.77  E-value: 1.26e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  331 IYCAEDLHLKKH---QSVNPQLEVELIGEKL--RTHMQTQT-----DNPIWNQILTFRIQLPCLsSYIKFRVLDCRKKDc 400
Cdd:cd00275     8 IISGQQLPKPKGdkgSIVDPYVEVEIHGLPAddSAKFKTKVvknngFNPVWNETFEFDVTVPEL-AFLRFVVYDEDSGD- 85

                          90       100       110
                  ....*....|....*....|....*....|...
gi 767920460  401 PDEIGTASLSLNQI----------SSTGEEIEG 423
Cdd:cd00275    86 DDFLGQACLPLDSLrqgyrhvpllDSKGEPLEL 118
C2 pfam00168
C2 domain;
2-92 3.46e-07

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 49.62  E-value: 3.46e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460     2 LRLVVQSAK--IDPPLAPLPRP--CMSIDFRDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKKE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPyvKVYLLDGKQKKKTKVVKNTlNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*.
gi 767920460    77 RFIGLATVLLKPLLKQ 92
Cdd:pfam00168   80 DFIGEVRIPLSELDSG 95
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 2-93 4.34e-07

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: 49.41  E-value: 4.34e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460      2 LRLVVQSAK--IDPPLAPLPRPCMSIDF---RDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKK 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLdgdPKEKKKTKVVKNTlNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90
                    ....*....|....*...
gi 767920460     76 ERFIGLATVLLKPLLKQP 93
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGG 96
FerA pfam08165
FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.
 620-670 6.92e-07

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


Pssm-ID: 462389  Cd Length: 65  Bit Score: 47.58  E-value: 6.92e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 767920460   620 WEKLLRELAEDCKRPLPCMTYQPKATSLDRKRWQLRSLLLQELAQKAKQAK 670
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALKLR 65
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 169-270 1.48e-06

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 47.83  E-value: 1.48e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  169 VRVKVFEARQL----MGNNIKPVVKVSIAG-QQHQTRIKMGN-NPFFNEIFfqNFHEVPAKffDETILIQVVNSSAMRYK 242
Cdd:cd00030     1 LRVTVIEARNLpakdLNGKSDPYVKVSLGGkQKFKTKVVKNTlNPVWNETF--EFPVLDPE--SDTLTVEVWDKDRFSKD 76

                          90       100
                  ....*....|....*....|....*...
gi 767920460  243 AEIGRFQTDIGFIYHSPGHTllRKWLGL 270
Cdd:cd00030    77 DFLGEVEIPLSELLDSGKEG--ELWLPL 102
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 168-264 1.89e-06

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: 47.48  E-value: 1.89e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460    168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQ---HQTRIKMGN-NPFFNEIFFqnFHEVPakFFDETILIQVVNSSAM 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPkekKKTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 767920460    240 RYKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
168-270 9.73e-06

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 45.77  E-value: 9.73e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460   168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQH--QTRIKMGN-NPFFNEIFFqnFhEVPAkFFDETILIQVVNSSAMR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQkkKTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 767920460   241 YKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104
C2 pfam00168
C2 domain;
1077-1190 1.39e-05

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 45.00  E-value: 1.39e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  1077 QLFCYIYQARNLVSNQILTFQGPFIRVVFL--NHSQCTQTLRSSAGPTWAQTLIFQhllLYENPQDTkespplVVLELWQ 1154
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 767920460  1155 RDFWGKESLWGRsvwppmVWLDLQDRIL--PPMRWHPL 1190
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSgeGLDGWYPL 104
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1078-1190 3.03e-05

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 43.98  E-value: 3.03e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460 1078 LFCYIYQARNLVSNQILTFQGPFIRVVFLN-HSQCTQTLRSSAGPTWAQTLIFQHlllyenpqdTKESPPLVVLELWQRD 1156
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGkQKFKTKVVKNTLNPVWNETFEFPV---------LDPESDTLTVEVWDKD 71

                          90       100       110
                  ....*....|....*....|....*....|....
gi 767920460 1157 FWGKESLWGRSVWPPMvwlDLQDRILPPMRWHPL 1190
Cdd:cd00030    72 RFSKDDFLGEVEIPLS---ELLDSGKEGELWLPL 102
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 31-102 1.09e-04

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 42.44  E-value: 1.09e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767920460   31 KKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKKERFIGLATVLLKPLLKQPSEVLFVKDL 102
Cdd:cd00030    33 KFKTKVVKNTlNPVWNETFEFPV---LDPESDTLTVEVWDKDRFSKDDFLGEVEIPLSELLDSGKEGELWLPL 102
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 171-248 1.34e-04

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: 42.96  E-value: 1.34e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  171 VKVFEARQLM----GNNIKPVVKVSIAGQ-----QHQTRIKMGN-NPFFNEIFfqNFhEVPAKFFDE-TILIQVVNSSAM 239
Cdd:cd00276    18 VVVLKARNLPpsdgKGLSDPYVKVSLLQGgkklkKKKTSVKKGTlNPVFNEAF--SF-DVPAEQLEEvSLVITVVDKDSV 94


                  ....*....
gi 767920460  240 RYKAEIGRF 248
Cdd:cd00276    95 GRNEVIGQV 103
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 327-414 2.29e-04

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: 42.26  E-value: 2.29e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  327 LQLFIYCAEDLHLKKHQSVNPQLEVELIGEKLR-THMQTQTDNPIWNQILTFRIQlPclSSYIKFRVLDCRKKDcPDE-I 404
Cdd:cd04021     4 LQITVESAKLKSNSKSFKPDPYVEVTVDGQPPKkTEVSKKTSNPKWNEHFTVLVT-P--QSTLEFKVWSHHTLK-ADVlL 79

                          90
                  ....*....|
gi 767920460  405 GTASLSLNQI 414
Cdd:cd04021    80 GEASLDLSDI 89
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 329-414 2.42e-04

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: 41.78  E-value: 2.42e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  329 LFIY--CAEDLHLKKHQS-VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPcLSSYIKFRVLDcRKKDCpdEIG 405
Cdd:cd04050     2 LFVYldSAKNLPLAKSTKePSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNP-ENQELEIEVKD-DKTGK--SLG 77


                  ....*....
gi 767920460  406 TASLSLNQI 414
Cdd:cd04050    78 SLTLPLSEL 86
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 1078-1171 4.00e-04

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


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 41.70  E-value: 4.00e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460 1078 LFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQhllLYENPqdtkesPPLVVLELWQRDF 1157
Cdd:cd04025     2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFE---LMEGA------DSPLSVEVWDWDL 72

                          90
                  ....*....|....
gi 767920460 1158 WGKESLWGRSVWPP 1171
Cdd:cd04025    73 VSKNDFLGKVVFSI 86
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 334-422 4.19e-04

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: 41.80  E-value: 4.19e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  334 AEDLHLKK-HQSVNPQLEVELI--GEKL---RTHMQTQTDNPIWNQILTFRI---QLPCLSsyIKFRVLDCRKKDCPDEI 404
Cdd:cd00276    23 ARNLPPSDgKGLSDPYVKVSLLqgGKKLkkkKTSVKKGTLNPVFNEAFSFDVpaeQLEEVS--LVITVVDKDSVGRNEVI 100

                          90
                  ....*....|....*...
gi 767920460  405 GTASLSLNqisSTGEEIE 422
Cdd:cd00276   101 GQVVLGPD---SGGEELE 115
FerI pfam08151
FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...
 273-312 5.14e-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: 39.07  E-value: 5.14e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 767920460   273 PNNPGSGVTGYLKVTIYALGVGDQALIDQKLLYGTDDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 31-94 5.57e-04

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 41.06  E-value: 5.57e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767920460   31 KKRTRVVE--GNDPVWNETLIWHLWNRPLE-NDSFLQVTLQDMGSQKKERFIGLATVLLKPLLKQPS 94
Cdd:cd04051    34 KQSTPVDRdgGTNPTWNETLRFPLDERLLQqGRLALTIEVYCERPSLGDKLIGEVRVPLKDLLDGAS 100
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 347-430 8.39e-04

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: 40.24  E-value: 8.39e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  347 PQLEVELIGEKL-RTHMQTQTDNPIWNQilTFRIQLPCLS-SYIKFRVLDCRKKDCPDEIGTASLSLNQISS-------- 416
Cdd:cd04040    22 PFVKFYLNGEKVfKTKTIKKTLNPVWNE--SFEVPVPSRVrAVLKVEVYDWDRGGKDDLLGSAYIDLSDLEPeetteltl 99

                          90
                  ....*....|....*.
gi 767920460  417 --TGEEIEGVYSGFLP 430
Cdd:cd04040   100 plDGQGGGKLGAVFLP 115
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 344-443 1.13e-03

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: 40.77  E-value: 1.13e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  344 SVNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSsyIKFRVLDcrkKDCP---DEIGTASLSL--------- 411
Cdd:cd04038    21 SSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP--LKLEVFD---KDTFskdDSMGEAEIDLeplveaakl 95

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 767920460  412 --NQISSTGEEIEGVYSGFLPCFG-PSFLTLHGGK 443
Cdd:cd04038    96 dhLRDTPGGTQIKKVLPSVENCLAsESHITWKDGK 130
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1077-1188 1.67e-03

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: 39.01  E-value: 1.67e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460   1077 QLFCYIYQARNLVSNQILTFQGPFIRVVFLN---HSQCTQTLRSSAGPTWAQTLIFqhlllYENPQDTKEspplVVLELW 1153
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEF-----EVPPPELAE----LEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 767920460   1154 QRDFWGKESLWGRsvwppmVWLDLQDRILPPMRWH 1188
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSDLLLGGRHEK 100
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 345-397 2.92e-03

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 38.71  E-value: 2.92e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 767920460  345 VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLP---CLSSYIKFRVLDCRK 397
Cdd:cd04011    21 IDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHESpdeLFDKIIKISVYDSRS 76
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 346-420 3.54e-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: 38.82  E-value: 3.54e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767920460  346 NPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLpcLSSYIKFRVLDCRKKDCPDEIGTASLSLNQISStGEE 420
Cdd:cd08377    23 DPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKD--IHDVLEVTVYDEDKDKKPEFLGKVAIPLLSIKN-GER 94
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
 2-91 4.63e-03

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: 38.50  E-value: 4.63e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460    2 LRLVVQSA-KIdpPLAPLPRPCMSIDFRDIK-KRTRVVEGNDPVWNETLIwhLWNRPLENDSFlQVTLQDMGSQKKERFI 79
Cdd:cd08400     6 LQLNVLEAhKL--PVKHVPHPYCVISLNEVKvARTKVREGPNPVWSEEFV--FDDLPPDVNSF-TISLSNKAKRSKDSEI 80

                          90
                  ....*....|..
gi 767920460   80 GLATVLLKPLLK 91
Cdd:cd08400    81 AEVTVQLSKLQN 92
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 31-80 5.46e-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: 38.33  E-value: 5.46e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767920460   31 KKRTRVVEGN-DPVWNETLIWHLWNRPLENDSfLQVTLQDMGSQKKERFIG 80
Cdd:cd00276    52 KKKTSVKKGTlNPVFNEAFSFDVPAEQLEEVS-LVITVVDKDSVGRNEVIG 101
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 334-379 7.21e-03

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


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 38.09  E-value: 7.21e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 767920460  334 AEDLHLK-KHQSVNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRI 379
Cdd:cd04022     9 AQDLMPKdGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNV 55
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 340-419 7.43e-03

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


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 38.00  E-value: 7.43e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767920460  340 KKHQSVNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCL-SSYIKFRVLDCRKKDCPDEIGTASLSLNQISSTG 418
Cdd:cd08373    10 GLKGKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGSPDpDESLEIVVKDYEKVGRNRLIGSATVSLQDLVSEG 89


                  .
gi 767920460  419 E 419
Cdd:cd08373    90 L 90
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1085-1130 8.22e-03

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


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 38.38  E-value: 8.22e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 767920460 1085 ARNLVSnqiltfqgPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQ 1130
Cdd:cd04018    31 KKELVD--------PYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFP 68
C2C_MCTP_PRT_plant cd04019
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 169-234 8.85e-03

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


Pssm-ID: 175986 [Multi-domain]  Cd Length: 150  Bit Score: 38.03  E-value: 8.85e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767920460  169 VRVKVFEARQL--MGNNIKP--VVKVSIAGQQHQTRIKM--GNNPFFNE--IFfqnfheVPAKFFDETILIQVV 234
Cdd:cd04019     2 LRVTVIEAQDLvpSDKNRVPevFVKAQLGNQVLRTRPSQtrNGNPSWNEelMF------VAAEPFEDHLILSVE 69
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 365-420 9.41e-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: 37.70  E-value: 9.41e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 767920460  365 QTDNPIWNQILTFRIQLPCLS--SYIKFRVLDCRKKDCPDEIGTASLSLNQISSTGEE 420
Cdd:cd04049    43 DGRNPEWNEKFKFTVEYPGWGgdTKLILRIMDKDNFSDDDFIGEATIHLKGLFEEGVE 100
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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