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Conserved domains on  [gi|459215035|ref|NP_001264005|]
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fer-1-like protein 5 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
C2F_Ferlin cd08374
C2 domain sixth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1722-1854 3.94e-65

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


:

Pssm-ID: 176020  Cd Length: 133  Bit Score: 216.76  E-value: 3.94e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1722 QLRCIIWSTAEVDLVQETFSKEKMSDIYVKGWLFGLEEDTQKTDVHYHSLTGEATFNWRFIFTMDYLTTERACVQSQKDY 1801
Cdd:cd08374     1 ELRVIVWNTRDVLNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKEH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 459215035 1802 IWSLDPTSTKFPARLMIQIWDNDFFSPDDFLGVLELDLSDMPLPAQNIKQCSL 1854
Cdd:cd08374    81 FWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1487-1610 1.61e-56

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


:

Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 191.99  E-value: 1.61e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1487 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADDE 1566
Cdd:cd04037     1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 459215035 1567 IGSTVIDLENRLLSGFGARCGLSKSYCKSGPFKWRDQMTPSYLL 1610
Cdd:cd04037    81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1077-1212 2.22e-41

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


:

Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 149.23  E-value: 2.22e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1077 YQLFCYIYQARNLMYNQILTFQEPFIQVVFLNHSLCTQTLRSSAAPTWSQSIIFQHLLLFEDPKDTRENPPLVVLELWQH 1156
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 459215035 1157 DSRGNKILWGRSMWPPVVWLGLQDWVFTPLRWHPLVReLGEEEGEILASCELILET 1212
Cdd:cd04017    81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYK-GGQSAGELLAAFELIEVT 135
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 164-271 1.64e-38

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


:

Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 140.02  E-value: 1.64e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  164 PQHFQVRVKVFEARQLLGNNIKPVVKVNIADQQHLTRIKMGNN-PFFNEIFFQNFHEVPAKFFEENISIEVVDSAASRSK 242
Cdd:cd04011     1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                          90       100
                  ....*....|....*....|....*....
gi 459215035  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLC 271
Cdd:cd04011    81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLT 109
FerB pfam08150
FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.
 691-763 2.54e-28

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


:

Pssm-ID: 462376  Cd Length: 76  Bit Score: 109.61  E-value: 2.54e-28
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 459215035   691 PQESLPDVLIWLMSRQQRVAYARVPAHTVLFSPAgPLSSGKFCGKIQNILLQYPE----GEGQDTFPASLRVCMWLG 763
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 ...
 5-134 3.76e-21

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


The actual alignment was detected with superfamily member cd08373:

Pssm-ID: 472691 [Multi-domain]  Cd Length: 127  Bit Score: 90.78  E-value: 3.76e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035    5 VVESASINPPLSTTPKAFVTVYFRDMMKRTRVEEGHD-PIWNETLIWHLWNQPlENDSFLKVILQDSVSKKKERFIGLAT 83
Cdd:cd08373     1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENELnPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 459215035   84 VPLKRLAqrpKEVMFVRDLILLNHSMKPTNCTVTLHVAQIYDQDTEMTGNE 134
Cdd:cd08373    80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 328-467 9.51e-19

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: 84.99  E-value: 9.51e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  328 FFIYCAEDL-----------HFGTHKSAT----PVLEVELIGDKLRTKPQNPSDNPIWNQILTFQIQLPCLSSYIKFRVM 392
Cdd:cd04018     4 FKIYRAEDLpqmdsgimanvKKAFLGEKKelvdPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIR 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 459215035  393 DCSKYKCQDEIGSASLCLSQISSTGEEiqgmysGFLPCFGPSFLTLRGgkkPPfrTSEEGTCIMDAVQHGL----AYRG 467
Cdd:cd04018    84 DWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYG---SP--REYSLLDDHQDLNEGLgegvAYRG 151
Ferlin_C super family cl24672
Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...
 1870-1983 4.59e-12

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


The actual alignment was detected with superfamily member pfam16165:

Pssm-ID: 435183  Cd Length: 154  Bit Score: 65.95  E-value: 4.59e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1870 RISLFKKTNVTGWWP----------------------------------CQVLD--GDKWRLSGKVKMTLEMLSEREALI 1913
Cdd:pfam16165    2 RVSIFRAKRMKGWWPfiklksqedfereereakkkkkkknkrsekkpedLEFKDasGNTFLLMGKVEAEFELLTVEEAEK 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1914 RPAGRGQSEPNQfpmLHPPERNDSFLLWYQSPIKNFCYAVCKRYRSKIICLVVTLVIGFILLNFVYSAPS 1983
Cdd:pfam16165   82 SPVGKGRKEPEP---LEKPNRPKTSFSWFVNPMKTFIFFIWRRYKKYIIALLILAILALFLFLILYTLPG 148
DysFN smart00693
Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...
 781-836 1.34e-07

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: 50.22  E-value: 1.34e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 459215035    781 VYAETYENQAKTRD-DWGQQGLYHCPNFSDVMGRK-ALPKTDFKAPPGWHWKDD-WVVE 836
Cdd:smart00693    4 FTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDDnWSLD 62
FerA super family cl06973
FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.
 619-649 1.92e-05

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


The actual alignment was detected with superfamily member pfam08165:

Pssm-ID: 462389  Cd Length: 65  Bit Score: 44.11  E-value: 1.92e-05
                           10        20        30
                   ....*....|....*....|....*....|.
gi 459215035   619 WEKLLKELQEDCRRPLPCMTDQPRANSLDRN 649
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQ 45
FerI super family cl06959
FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...
 276-297 6.04e-04

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


The actual alignment was detected with superfamily member pfam08151:

Pssm-ID: 462377  Cd Length: 52  Bit Score: 39.45  E-value: 6.04e-04
                           10        20
                   ....*....|....*....|..
gi 459215035   276 TTSGVRGYLKVTICALGVGDQA 297
Cdd:pfam08151    6 ISAGVKGYLKVDISVLGKGDEP 27
 
Name Accession Description Interval E-value
C2F_Ferlin cd08374
C2 domain sixth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1722-1854 3.94e-65

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


Pssm-ID: 176020  Cd Length: 133  Bit Score: 216.76  E-value: 3.94e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1722 QLRCIIWSTAEVDLVQETFSKEKMSDIYVKGWLFGLEEDTQKTDVHYHSLTGEATFNWRFIFTMDYLTTERACVQSQKDY 1801
Cdd:cd08374     1 ELRVIVWNTRDVLNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKEH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 459215035 1802 IWSLDPTSTKFPARLMIQIWDNDFFSPDDFLGVLELDLSDMPLPAQNIKQCSL 1854
Cdd:cd08374    81 FWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1487-1610 1.61e-56

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


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 191.99  E-value: 1.61e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1487 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADDE 1566
Cdd:cd04037     1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 459215035 1567 IGSTVIDLENRLLSGFGARCGLSKSYCKSGPFKWRDQMTPSYLL 1610
Cdd:cd04037    81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1077-1212 2.22e-41

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


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 149.23  E-value: 2.22e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1077 YQLFCYIYQARNLMYNQILTFQEPFIQVVFLNHSLCTQTLRSSAAPTWSQSIIFQHLLLFEDPKDTRENPPLVVLELWQH 1156
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 459215035 1157 DSRGNKILWGRSMWPPVVWLGLQDWVFTPLRWHPLVReLGEEEGEILASCELILET 1212
Cdd:cd04017    81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYK-GGQSAGELLAAFELIEVT 135
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 164-271 1.64e-38

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


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 140.02  E-value: 1.64e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  164 PQHFQVRVKVFEARQLLGNNIKPVVKVNIADQQHLTRIKMGNN-PFFNEIFFQNFHEVPAKFFEENISIEVVDSAASRSK 242
Cdd:cd04011     1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                          90       100
                  ....*....|....*....|....*....
gi 459215035  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLC 271
Cdd:cd04011    81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLT 109
FerB pfam08150
FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.
 691-763 2.54e-28

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


Pssm-ID: 462376  Cd Length: 76  Bit Score: 109.61  E-value: 2.54e-28
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 459215035   691 PQESLPDVLIWLMSRQQRVAYARVPAHTVLFSPAgPLSSGKFCGKIQNILLQYPE----GEGQDTFPASLRVCMWLG 763
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKYPGkkakGPAGWEIPAKLRVYLWLG 76
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 5-134 3.76e-21

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


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 90.78  E-value: 3.76e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035    5 VVESASINPPLSTTPKAFVTVYFRDMMKRTRVEEGHD-PIWNETLIWHLWNQPlENDSFLKVILQDSVSKKKERFIGLAT 83
Cdd:cd08373     1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENELnPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 459215035   84 VPLKRLAqrpKEVMFVRDLILLNHSMKPTNCTVTLHVAQIYDQDTEMTGNE 134
Cdd:cd08373    80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 328-467 9.51e-19

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


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 84.99  E-value: 9.51e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  328 FFIYCAEDL-----------HFGTHKSAT----PVLEVELIGDKLRTKPQNPSDNPIWNQILTFQIQLPCLSSYIKFRVM 392
Cdd:cd04018     4 FKIYRAEDLpqmdsgimanvKKAFLGEKKelvdPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIR 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 459215035  393 DCSKYKCQDEIGSASLCLSQISSTGEEiqgmysGFLPCFGPSFLTLRGgkkPPfrTSEEGTCIMDAVQHGL----AYRG 467
Cdd:cd04018    84 DWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYG---SP--REYSLLDDHQDLNEGLgegvAYRG 151
C2 pfam00168
C2 domain;
1486-1580 2.10e-14

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 70.81  E-value: 2.10e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1486 CLVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADD 1565
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80

                           90
                   ....*....|....*
gi 459215035  1566 EIGSTVIDLENRLLS 1580
Cdd:pfam00168   81 FIGEVRIPLSELDSG 95
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1487-1581 3.34e-13

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 67.51  E-value: 3.34e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035   1487 LVRVYLIRAINLQPQDYNGLCDPYVILKL-GQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADD 1565
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLdGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                            90
                    ....*....|....*.
gi 459215035   1566 EIGSTVIDLENRLLSG 1581
Cdd:smart00239   81 FIGQVTIPLSDLLLGG 96
Ferlin_C pfam16165
Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...
 1870-1983 4.59e-12

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


Pssm-ID: 435183  Cd Length: 154  Bit Score: 65.95  E-value: 4.59e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1870 RISLFKKTNVTGWWP----------------------------------CQVLD--GDKWRLSGKVKMTLEMLSEREALI 1913
Cdd:pfam16165    2 RVSIFRAKRMKGWWPfiklksqedfereereakkkkkkknkrsekkpedLEFKDasGNTFLLMGKVEAEFELLTVEEAEK 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1914 RPAGRGQSEPNQfpmLHPPERNDSFLLWYQSPIKNFCYAVCKRYRSKIICLVVTLVIGFILLNFVYSAPS 1983
Cdd:pfam16165   82 SPVGKGRKEPEP---LEKPNRPKTSFSWFVNPMKTFIFFIWRRYKKYIIALLILAILALFLFLILYTLPG 148
C2 pfam00168
C2 domain;
2-92 3.55e-08

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 53.09  E-value: 3.55e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035     2 LRVVVESAS--INPPLSTTPKAFVTVYFRD--MMKRTRV-EEGHDPIWNETLIWHLwnqPLENDSFLKVILQDSVSKKKE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPYVKVYLLDgkQKKKTKVvKNTLNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*.
gi 459215035    77 RFIGLATVPLKRLAQR 92
Cdd:pfam00168   80 DFIGEVRIPLSELDSG 95
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 325-413 9.89e-08

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: 51.72  E-value: 9.89e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035    325 YLQFFIYCAEDL-HFGTHKSATPVLEVELIGD---KLRTKPQNPSDNPIWNQILTFQIQLPCLSSyIKFRVMDCSKYKCQ 400
Cdd:smart00239    1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAE-LEIEVYDKDRFGRD 79

                            90
                    ....*....|...
gi 459215035    401 DEIGSASLCLSQI 413
Cdd:smart00239   80 DFIGQVTIPLSDL 92
DysFN smart00693
Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...
 781-836 1.34e-07

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: 50.22  E-value: 1.34e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 459215035    781 VYAETYENQAKTRD-DWGQQGLYHCPNFSDVMGRK-ALPKTDFKAPPGWHWKDD-WVVE 836
Cdd:smart00693    4 FTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDDnWSLD 62
C2 pfam00168
C2 domain;
325-421 5.27e-07

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 50.01  E-value: 5.27e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035   325 YLQFFIYCAEDLH----FGThksATPVLEVELIGD--KLRTKPQNPSDNPIWNQILTFQIQLPcLSSYIKFRVMDCSKYK 398
Cdd:pfam00168    2 RLTVTVIEAKNLPpkdgNGT---SDPYVKVYLLDGkqKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFG 77

                           90       100
                   ....*....|....*....|...
gi 459215035   399 CQDEIGSASLCLSQISSTGEEIQ 421
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLDG 100
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 2-98 5.76e-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: 49.79  E-value: 5.76e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035      2 LRVVVESAS--INPPLSTTPKAFVTVYFRDM---MKRTRV-EEGHDPIWNETLIWHLwnqPLENDSFLKVILQDSVSKKK 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLDGDpkeKKKTKVvKNTLNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90       100
                    ....*....|....*....|...
gi 459215035     76 ERFIGLATVPLKRLAQRPKEVMF 98
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGGRHEKL 101
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1745-1844 1.87e-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: 48.25  E-value: 1.87e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035   1745 MSDIYVKGWLFGLEEDTQKTDVHYHSLTgeATFNWRFIFTMDYLTTeracvqsqkdyiwsldptstkfpARLMIQIWDND 1824
Cdd:smart00239   20 KSDPYVKVSLDGDPKEKKKTKVVKNTLN--PVWNETFEFEVPPPEL-----------------------AELEIEVYDKD 74

                            90       100
                    ....*....|....*....|
gi 459215035   1825 FFSPDDFLGVLELDLSDMPL 1844
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLLL 94
FerA pfam08165
FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.
 619-649 1.92e-05

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


Pssm-ID: 462389  Cd Length: 65  Bit Score: 44.11  E-value: 1.92e-05
                           10        20        30
                   ....*....|....*....|....*....|.
gi 459215035   619 WEKLLKELQEDCRRPLPCMTDQPRANSLDRN 649
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQ 45
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 168-264 7.29e-05

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: 43.63  E-value: 7.29e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035    168 QVRVKVFEARQLLGNNIK----PVVKVNIADQQHL---TRIKMGN-NPFFNEIFFqnFHEVPakFFEENISIEVVDSAAS 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPKEkkkTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 459215035    240 RSKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
168-270 7.45e-05

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 43.85  E-value: 7.45e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035   168 QVRVKVFEARQLLGNNIK----PVVKVNIADQQHL--TRIKMGN-NPFFNEIFFqnFhEVPAkFFEENISIEVVDSAASR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQKkkTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 459215035   241 SKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1472-1578 8.17e-05

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 47.83  E-value: 8.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1472 QFSAWPEIEDFPQMCLVR------VYLIRAINLQPQDYNGLCDPYVILKLGQTKLgsrdsyYPN-----TLDPIFGMMYE 1540
Cdd:COG5038  1020 QVSYTPVPVKLPPVEMVEnsgyltIMLRSGENLPSSDENGYSDPFVKLFLNEKSV------YKTkvvkkTLNPVWNEEFT 1093

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 459215035 1541 LTCNIPLEKDLEIQLFDFDLITADDEIGSTVIDLENRL 1578
Cdd:COG5038  1094 IEVLNRVKDVLTINVNDWDSGEKNDLLGTAEIDLSKLE 1131
FerI pfam08151
FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...
 276-297 6.04e-04

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


Pssm-ID: 462377  Cd Length: 52  Bit Score: 39.45  E-value: 6.04e-04
                           10        20
                   ....*....|....*....|..
gi 459215035   276 TTSGVRGYLKVTICALGVGDQA 297
Cdd:pfam08151    6 ISAGVKGYLKVDISVLGKGDEP 27
C2 pfam00168
C2 domain;
1078-1191 1.56e-03

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 39.99  E-value: 1.56e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1078 QLFCYIYQARNLMYNQILTFQEPFIQVVFL--NHSLCTQTLRSSAAPTWSQSIIFQhllLFEDPKDTrenpplVVLELWQ 1155
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 459215035  1156 HDSRGNKILWGRsmwppvVWLGLQDWVFTPL--RWHPL 1191
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSGEGldGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1078-1180 1.81e-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: 39.78  E-value: 1.81e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035   1078 QLFCYIYQARNLMYNQILTFQEPFIQVVFLN---HSLCTQTLRSSAAPTWSQSIIFQhlllfEDPKDTREnpplVVLELW 1154
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFE-----VPPPELAE----LEIEVY 71

                            90       100
                    ....*....|....*....|....*.
gi 459215035   1155 QHDSRGNKILWGRsmwppvVWLGLQD 1180
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSD 91
C2 pfam00168
C2 domain;
1745-1847 2.89e-03

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 39.22  E-value: 2.89e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1745 MSDIYVKGWLFGLEEdTQKTDVHYHSLTgeATFNWRFIFTMDYLTTERacvqsqkdyiwsldptstkfparLMIQIWDND 1824
Cdd:pfam00168   21 TSDPYVKVYLLDGKQ-KKKTKVVKNTLN--PVWNETFTFSVPDPENAV-----------------------LEIEVYDYD 74

                           90       100
                   ....*....|....*....|...
gi 459215035  1825 FFSPDDFLGVLELDLSDMPLPAQ 1847
Cdd:pfam00168   75 RFGRDDFIGEVRIPLSELDSGEG 97
 
Name Accession Description Interval E-value
C2F_Ferlin cd08374
C2 domain sixth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1722-1854 3.94e-65

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


Pssm-ID: 176020  Cd Length: 133  Bit Score: 216.76  E-value: 3.94e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1722 QLRCIIWSTAEVDLVQETFSKEKMSDIYVKGWLFGLEEDTQKTDVHYHSLTGEATFNWRFIFTMDYLTTERACVQSQKDY 1801
Cdd:cd08374     1 ELRVIVWNTRDVLNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKEH 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 459215035 1802 IWSLDPTSTKFPARLMIQIWDNDFFSPDDFLGVLELDLSDMPLPAQNIKQCSL 1854
Cdd:cd08374    81 FWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1487-1610 1.61e-56

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


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 191.99  E-value: 1.61e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1487 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADDE 1566
Cdd:cd04037     1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 459215035 1567 IGSTVIDLENRLLSGFGARCGLSKSYCKSGPFKWRDQMTPSYLL 1610
Cdd:cd04037    81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1077-1212 2.22e-41

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


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 149.23  E-value: 2.22e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1077 YQLFCYIYQARNLMYNQILTFQEPFIQVVFLNHSLCTQTLRSSAAPTWSQSIIFQHLLLFEDPKDTRENPPLVVLELWQH 1156
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 459215035 1157 DSRGNKILWGRSMWPPVVWLGLQDWVFTPLRWHPLVReLGEEEGEILASCELILET 1212
Cdd:cd04017    81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYK-GGQSAGELLAAFELIEVT 135
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 164-271 1.64e-38

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


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 140.02  E-value: 1.64e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  164 PQHFQVRVKVFEARQLLGNNIKPVVKVNIADQQHLTRIKMGNN-PFFNEIFFQNFHEVPAKFFEENISIEVVDSAASRSK 242
Cdd:cd04011     1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                          90       100
                  ....*....|....*....|....*....
gi 459215035  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLC 271
Cdd:cd04011    81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLT 109
FerB pfam08150
FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.
 691-763 2.54e-28

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


Pssm-ID: 462376  Cd Length: 76  Bit Score: 109.61  E-value: 2.54e-28
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 459215035   691 PQESLPDVLIWLMSRQQRVAYARVPAHTVLFSPAgPLSSGKFCGKIQNILLQYPE----GEGQDTFPASLRVCMWLG 763
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKYPGkkakGPAGWEIPAKLRVYLWLG 76
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 5-134 3.76e-21

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


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 90.78  E-value: 3.76e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035    5 VVESASINPPLSTTPKAFVTVYFRDMMKRTRVEEGHD-PIWNETLIWHLWNQPlENDSFLKVILQDSVSKKKERFIGLAT 83
Cdd:cd08373     1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENELnPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 459215035   84 VPLKRLAqrpKEVMFVRDLILLNHSMKPTNCTVTLHVAQIYDQDTEMTGNE 134
Cdd:cd08373    80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 328-467 9.51e-19

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


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 84.99  E-value: 9.51e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  328 FFIYCAEDL-----------HFGTHKSAT----PVLEVELIGDKLRTKPQNPSDNPIWNQILTFQIQLPCLSSYIKFRVM 392
Cdd:cd04018     4 FKIYRAEDLpqmdsgimanvKKAFLGEKKelvdPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIR 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 459215035  393 DCSKYKCQDEIGSASLCLSQISSTGEEiqgmysGFLPCFGPSFLTLRGgkkPPfrTSEEGTCIMDAVQHGL----AYRG 467
Cdd:cd04018    84 DWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYG---SP--REYSLLDDHQDLNEGLgegvAYRG 151
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1488-1576 2.07e-15

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 73.64  E-value: 2.07e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1488 VRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGsRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADDEI 1567
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKF-KTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDFL 79


                  ....*....
gi 459215035 1568 GSTVIDLEN 1576
Cdd:cd00030    80 GEVEIPLSE 88
C2 pfam00168
C2 domain;
1486-1580 2.10e-14

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 70.81  E-value: 2.10e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1486 CLVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADD 1565
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80

                           90
                   ....*....|....*
gi 459215035  1566 EIGSTVIDLENRLLS 1580
Cdd:pfam00168   81 FIGEVRIPLSELDSG 95
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1487-1581 3.34e-13

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 67.51  E-value: 3.34e-13
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035   1487 LVRVYLIRAINLQPQDYNGLCDPYVILKL-GQTKLGSRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADD 1565
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLdGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                            90
                    ....*....|....*.
gi 459215035   1566 EIGSTVIDLENRLLSG 1581
Cdd:smart00239   81 FIGQVTIPLSDLLLGG 96
Ferlin_C pfam16165
Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...
 1870-1983 4.59e-12

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


Pssm-ID: 435183  Cd Length: 154  Bit Score: 65.95  E-value: 4.59e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1870 RISLFKKTNVTGWWP----------------------------------CQVLD--GDKWRLSGKVKMTLEMLSEREALI 1913
Cdd:pfam16165    2 RVSIFRAKRMKGWWPfiklksqedfereereakkkkkkknkrsekkpedLEFKDasGNTFLLMGKVEAEFELLTVEEAEK 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1914 RPAGRGQSEPNQfpmLHPPERNDSFLLWYQSPIKNFCYAVCKRYRSKIICLVVTLVIGFILLNFVYSAPS 1983
Cdd:pfam16165   82 SPVGKGRKEPEP---LEKPNRPKTSFSWFVNPMKTFIFFIWRRYKKYIIALLILAILALFLFLILYTLPG 148
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 1483-1581 2.86e-10

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


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 59.72  E-value: 2.86e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1483 PQMCLVRVYLIRAINLQPQDYNGLCDPYVILKL-------GQTKLGSRdsyypnTLDPIFG--MMYELTCNIPLEKDLEI 1553
Cdd:cd08387    13 KDMGILNVKLIQARNLQPRDFSGTADPYCKVRLlpdrsntKQSKIHKK------TLNPEFDesFVFEVPPQELPKRTLEV 86

                          90       100
                  ....*....|....*....|....*...
gi 459215035 1554 QLFDFDLITADDEIGSTVIDLENRLLSG 1581
Cdd:cd08387    87 LLYDFDQFSRDECIGVVELPLAEVDLSE 114
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1489-1576 4.26e-09

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


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 56.66  E-value: 4.26e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1489 RVYLIRAINLQPQD--YNGLCDPYVILKLGQTKLgsRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFDLITADDE 1566
Cdd:cd04024     4 RVHVVEAKDLAAKDrsGKGKSDPYAILSVGAQRF--KTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKDY 81

                          90
                  ....*....|
gi 459215035 1567 IGSTVIDLEN 1576
Cdd:cd04024    82 LGEFDIALEE 91
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 1487-1575 4.57e-09

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


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 56.95  E-value: 4.57e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1487 LVRVYLIRAINLQPQDYNGlCDPYVILKLGQTKLGSRDSYypNTLDPIFGMmyELTCNIP-LEKDLEIQLFDFDLITADD 1565
Cdd:cd04038     3 LLKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTRVIK--KNLNPVWNE--ELTLSVPnPMAPLKLEVFDKDTFSKDD 77

                          90
                  ....*....|
gi 459215035 1566 EIGSTVIDLE 1575
Cdd:cd04038    78 SMGEAEIDLE 87
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 1490-1581 6.85e-09

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 55.72  E-value: 6.85e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1490 VYLIRAINLQPQDYNGLCDPYVILKL--GQTKLGSRDS-YYPNTLDPIFG--MMYEltcNIP----LEKDLEIQLFDFDL 1560
Cdd:cd04031    20 VTVLQARDLPPRDDGSLRNPYVKVYLlpDRSEKSKRRTkTVKKTLNPEWNqtFEYS---NVRretlKERTLEVTVWDYDR 96

                          90       100
                  ....*....|....*....|.
gi 459215035 1561 ITADDEIGSTVIDLENRLLSG 1581
Cdd:cd04031    97 DGENDFLGEVVIDLADALLDD 117
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1486-1582 7.31e-09

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


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 55.76  E-value: 7.31e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1486 CLVRVYLIRAINLQPQDYN------GLCDPYVILKLGQTKLgsRDSYYPNTLDPIFGMMYELTCNIPLEKDLEIQLFDFD 1559
Cdd:cd08391     1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRVGAQTF--KSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDED 78

                          90       100
                  ....*....|....*....|...
gi 459215035 1560 lITADDEIGSTVIDLENRLLSGF 1582
Cdd:cd08391    79 -PDKDDFLGRLSIDLGSVEKKGF 100
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1487-1576 1.21e-08

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


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 54.95  E-value: 1.21e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1487 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYypNTLDPIFGMMYELtcNIPLEKD--LEIQLFDFDLITAD 1564
Cdd:cd08376     1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCS--KTLNPQWLEQFDL--HLFDDQSqiLEIEVWDKDTGKKD 76

                          90
                  ....*....|..
gi 459215035 1565 DEIGSTVIDLEN 1576
Cdd:cd08376    77 EFIGRCEIDLSA 88
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 326-420 2.85e-08

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: 53.22  E-value: 2.85e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  326 LQFFIYCAEDLH-FGTHKSATPVLEVELIGD-KLRTKPQNPSDNPIWNQILTFQIqLPCLSSYIKFRVMDCSKYKCQDEI 403
Cdd:cd00030     1 LRVTVIEARNLPaKDLNGKSDPYVKVSLGGKqKFKTKVVKNTLNPVWNETFEFPV-LDPESDTLTVEVWDKDRFSKDDFL 79

                          90
                  ....*....|....*..
gi 459215035  404 GSASLCLSQISSTGEEI 420
Cdd:cd00030    80 GEVEIPLSELLDSGKEG 96
C2 pfam00168
C2 domain;
2-92 3.55e-08

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 53.09  E-value: 3.55e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035     2 LRVVVESAS--INPPLSTTPKAFVTVYFRD--MMKRTRV-EEGHDPIWNETLIWHLwnqPLENDSFLKVILQDSVSKKKE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPYVKVYLLDgkQKKKTKVvKNTLNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*.
gi 459215035    77 RFIGLATVPLKRLAQR 92
Cdd:pfam00168   80 DFIGEVRIPLSELDSG 95
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 2-102 5.63e-08

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: 52.45  E-value: 5.63e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035    2 LRVVVESASINPP--LSTTPKAFVTVYFRDMMK-RTRV-EEGHDPIWNETLIWHLwnqPLENDSFLKVILQDSVSKKKER 77
Cdd:cd00030     1 LRVTVIEARNLPAkdLNGKSDPYVKVSLGGKQKfKTKVvKNTLNPVWNETFEFPV---LDPESDTLTVEVWDKDRFSKDD 77

                          90       100
                  ....*....|....*....|....*
gi 459215035   78 FIGLATVPLKRLAQRPKEVMFVRDL 102
Cdd:cd00030    78 FLGEVEIPLSELLDSGKEGELWLPL 102
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 325-413 9.89e-08

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: 51.72  E-value: 9.89e-08
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035    325 YLQFFIYCAEDL-HFGTHKSATPVLEVELIGD---KLRTKPQNPSDNPIWNQILTFQIQLPCLSSyIKFRVMDCSKYKCQ 400
Cdd:smart00239    1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGDpkeKKKTKVVKNTLNPVWNETFEFEVPPPELAE-LEIEVYDKDRFGRD 79

                            90
                    ....*....|...
gi 459215035    401 DEIGSASLCLSQI 413
Cdd:smart00239   80 DFIGQVTIPLSDL 92
DysFN smart00693
Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...
 781-836 1.34e-07

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: 50.22  E-value: 1.34e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 459215035    781 VYAETYENQAKTRD-DWGQQGLYHCPNFSDVMGRK-ALPKTDFKAPPGWHWKDD-WVVE 836
Cdd:smart00693    4 FTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDDnWSLD 62
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1488-1574 2.15e-07

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 51.41  E-value: 2.15e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1488 VRVYLIRAINLQPQDYNGLCDPYVILKLG-----QTKLGSRdsyypnTLDPIFGmmyElTCNIPL----EKDLEIQLFDF 1558
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKFYLNgekvfKTKTIKK------TLNPVWN---E-SFEVPVpsrvRAVLKVEVYDW 70

                          90
                  ....*....|....*.
gi 459215035 1559 DLITADDEIGSTVIDL 1574
Cdd:cd04040    71 DRGGKDDLLGSAYIDL 86
C2 pfam00168
C2 domain;
325-421 5.27e-07

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 50.01  E-value: 5.27e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035   325 YLQFFIYCAEDLH----FGThksATPVLEVELIGD--KLRTKPQNPSDNPIWNQILTFQIQLPcLSSYIKFRVMDCSKYK 398
Cdd:pfam00168    2 RLTVTVIEAKNLPpkdgNGT---SDPYVKVYLLDGkqKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFG 77

                           90       100
                   ....*....|....*....|...
gi 459215035   399 CQDEIGSASLCLSQISSTGEEIQ 421
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLDG 100
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 2-98 5.76e-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: 49.79  E-value: 5.76e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035      2 LRVVVESAS--INPPLSTTPKAFVTVYFRDM---MKRTRV-EEGHDPIWNETLIWHLwnqPLENDSFLKVILQDSVSKKK 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLDGDpkeKKKTKVvKNTLNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90       100
                    ....*....|....*....|...
gi 459215035     76 ERFIGLATVPLKRLAQRPKEVMF 98
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGGRHEKL 101
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1484-1576 7.99e-07

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


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 49.97  E-value: 7.99e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1484 QMCLvRVYLIRAINLQPQDYNGLCDPYVILKL-----GQTKLgsRDSYYPNTLDPIFG---MMYELTCNIPLEKDLEIQL 1555
Cdd:cd04035    14 NSAL-HCTIIRAKGLKAMDANGLSDPYVKLNLlpgasKATKL--RTKTVHKTRNPEFNetlTYYGITEEDIQRKTLRLLV 90

                          90       100
                  ....*....|....*....|.
gi 459215035 1556 FDFDLItADDEIGSTVIDLEN 1576
Cdd:cd04035    91 LDEDRF-GNDFLGETRIPLKK 110
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1487-1576 8.04e-07

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


Pssm-ID: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 49.97  E-value: 8.04e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1487 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQtKLGSRDSYYPNTLDPIFgmmYELTCnIPLE---KDLEIQLFDFDLITA 1563
Cdd:cd04042     1 QLDIHLKEGRNLAARDRGGTSDPYVKFKYGG-KTVYKSKTIYKNLNPVW---DEKFT-LPIEdvtQPLYIKVFDYDRGLT 75

                          90
                  ....*....|...
gi 459215035 1564 DDEIGSTVIDLEN 1576
Cdd:cd04042    76 DDFMGSAFVDLST 88
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 1487-1592 1.65e-06

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


Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 49.27  E-value: 1.65e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1487 LVRVYLIRAINLQPQDYNGLCDPYVILKLGQTK-LGSRDSYYPNT----LDPIFGMMYELTCNiPLEKDLEIQLFDFDLI 1561
Cdd:cd04033     1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPDgNGEIDSVQTKTikktLNPKWNEEFFFRVN-PREHRLLFEVFDENRL 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 459215035 1562 TADDEIGSTVIDLENRLLSGFGARCGLS-KSY 1592
Cdd:cd04033    80 TRDDFLGQVEVPLNNLPTETPGNERRYTfKDY 111
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1745-1844 1.87e-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: 48.25  E-value: 1.87e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035   1745 MSDIYVKGWLFGLEEDTQKTDVHYHSLTgeATFNWRFIFTMDYLTTeracvqsqkdyiwsldptstkfpARLMIQIWDND 1824
Cdd:smart00239   20 KSDPYVKVSLDGDPKEKKKTKVVKNTLN--PVWNETFEFEVPPPEL-----------------------AELEIEVYDKD 74

                            90       100
                    ....*....|....*....|
gi 459215035   1825 FFSPDDFLGVLELDLSDMPL 1844
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLLL 94
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 1490-1568 2.10e-06

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


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 48.95  E-value: 2.10e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1490 VYLIRAINLQPQDYNGLCDPYVILKL--GQTKLGSRDS-YYPNTLDPIFGMMYELtcNIPLEK----DLEIQLFDFDLIT 1562
Cdd:cd08405    19 VNIIKARNLKAMDINGTSDPYVKVWLmyKDKRVEKKKTvIKKRTLNPVFNESFIF--NIPLERlretTLIITVMDKDRLS 96


                  ....*.
gi 459215035 1563 ADDEIG 1568
Cdd:cd08405    97 RNDLIG 102
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 1489-1576 4.38e-06

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


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 48.00  E-value: 4.38e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1489 RVYLIRAINLQPQDYNGLCDPYVILKLG-----------QTKLGSrdsyypNTLDPIFGMMYELtcNIPLEKDLE---IQ 1554
Cdd:cd04009    19 RVEILNARNLLPLDSNGSSDPFVKVELLprhlfpdvptpKTQVKK------KTLFPLFDESFEF--NVPPEQCSVegaLL 90

                          90       100
                  ....*....|....*....|....*
gi 459215035 1555 LF---DFDLITADDEIGSTVIDLEN 1576
Cdd:cd04009    91 LFtvkDYDLLGSNDFEGEAFLPLND 115
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 350-413 6.52e-06

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


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 47.27  E-value: 6.52e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 459215035  350 VELIGDKL---RTKPQNPSDNPIWNQILTFQIQlPclSSYIKFRVMDCSKYKCQDEIGSASLCLSQI 413
Cdd:cd04021    26 VEVTVDGQppkKTEVSKKTSNPKWNEHFTVLVT-P--QSTLEFKVWSHHTLKADVLLGEASLDLSDI 89
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1484-1569 1.31e-05

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


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 46.57  E-value: 1.31e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1484 QMCLVrVYLIRAINLQPQDYNGLCDPYVILKL---GQTKLGSRDSYYPNTLDPIFG--MMYELTCNIPLEKDLEIQLFDF 1558
Cdd:cd08384    12 RRGLI-VGIIRCVNLAAMDANGYSDPFVKLYLkpdAGKKSKHKTQVKKKTLNPEFNeeFFYDIKHSDLAKKTLEITVWDK 90

                          90
                  ....*....|.
gi 459215035 1559 DLITADDEIGS 1569
Cdd:cd08384    91 DIGKSNDYIGG 101
FerA pfam08165
FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.
 619-649 1.92e-05

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


Pssm-ID: 462389  Cd Length: 65  Bit Score: 44.11  E-value: 1.92e-05
                           10        20        30
                   ....*....|....*....|....*....|.
gi 459215035   619 WEKLLKELQEDCRRPLPCMTDQPRANSLDRN 649
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQ 45
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 1487-1574 3.63e-05

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


Pssm-ID: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 44.94  E-value: 3.63e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1487 LVRVYLIRAINLQPQDYN-GLCDPYVILKLGQT-KLGSRDSYYPNTLDPIFgmmyELTC-------NIPLEKDLEIQLFD 1557
Cdd:cd04041     2 VLVVTIHRATDLPKADFGtGSSDPYVTASFAKFgKPLYSTRIIRKDLNPVW----EETWfvlvtpdEVKAGERLSCRLWD 77

                          90
                  ....*....|....*..
gi 459215035 1558 FDLITADDEIGSTVIDL 1574
Cdd:cd04041    78 SDRFTADDRLGRVEIDL 94
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 169-270 4.14e-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: 44.37  E-value: 4.14e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  169 VRVKVFEARQLLGNNIK----PVVKVNIADQQHL-TRIKMGN-NPFFNEIFfqNFHEVPAKffEENISIEVVDSAASRSK 242
Cdd:cd00030     1 LRVTVIEARNLPAKDLNgksdPYVKVSLGGKQKFkTKVVKNTlNPVWNETF--EFPVLDPE--SDTLTVEVWDKDRFSKD 76

                          90       100
                  ....*....|....*....|....*...
gi 459215035  243 AEIGRFQTDIGFIYHSPGHTllRKWLGL 270
Cdd:cd00030    77 DFLGEVEIPLSELLDSGKEG--ELWLPL 102
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 1490-1569 5.90e-05

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


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 44.56  E-value: 5.90e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1490 VYLIRAINLQPQDYNGLCDPYVILKL-----GQTKLGSRDsyYPNTLDPIFGM--MYELTCNiPLEKDLEIQLFDFDLIT 1562
Cdd:cd04026    17 VEVREAKNLIPMDPNGLSDPYVKLKLipdpkNETKQKTKT--IKKTLNPVWNEtfTFDLKPA-DKDRRLSIEVWDWDRTT 93


                  ....*..
gi 459215035 1563 ADDEIGS 1569
Cdd:cd04026    94 RNDFMGS 100
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 168-264 7.29e-05

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: 43.63  E-value: 7.29e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035    168 QVRVKVFEARQLLGNNIK----PVVKVNIADQQHL---TRIKMGN-NPFFNEIFFqnFHEVPakFFEENISIEVVDSAAS 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPKEkkkTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 459215035    240 RSKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
168-270 7.45e-05

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 43.85  E-value: 7.45e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035   168 QVRVKVFEARQLLGNNIK----PVVKVNIADQQHL--TRIKMGN-NPFFNEIFFqnFhEVPAkFFEENISIEVVDSAASR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQKkkTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 459215035   241 SKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1472-1578 8.17e-05

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 47.83  E-value: 8.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1472 QFSAWPEIEDFPQMCLVR------VYLIRAINLQPQDYNGLCDPYVILKLGQTKLgsrdsyYPN-----TLDPIFGMMYE 1540
Cdd:COG5038  1020 QVSYTPVPVKLPPVEMVEnsgyltIMLRSGENLPSSDENGYSDPFVKLFLNEKSV------YKTkvvkkTLNPVWNEEFT 1093

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 459215035 1541 LTCNIPLEKDLEIQLFDFDLITADDEIGSTVIDLENRL 1578
Cdd:COG5038  1094 IEVLNRVKDVLTINVNDWDSGEKNDLLGTAEIDLSKLE 1131
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 346-413 9.65e-05

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


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 44.07  E-value: 9.65e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 459215035  346 PVLEVELIGD------KLRTKP-QNPSDNPIWNQILTFQIQLPCLsSYIKFRVMDCSKyKCQDEIGSASLCLSQI 413
Cdd:cd00275    27 PYVEVEIHGLpaddsaKFKTKVvKNNGFNPVWNETFEFDVTVPEL-AFLRFVVYDEDS-GDDDFLGQACLPLDSL 99
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1746-1851 1.44e-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: 42.82  E-value: 1.44e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1746 SDIYVKGWLFGLEedTQKTDVHYHSLTgeatFNWRFIFTMDYLTTERAcvqsqkdyiwsldptstkfpaRLMIQIWDNDF 1825
Cdd:cd00030    20 SDPYVKVSLGGKQ--KFKTKVVKNTLN----PVWNETFEFPVLDPESD---------------------TLTVEVWDKDR 72

                          90       100
                  ....*....|....*....|....*.
gi 459215035 1826 FSPDDFLGVLELDLSDMPLPAQNIKQ 1851
Cdd:cd00030    73 FSKDDFLGEVEIPLSELLDSGKEGEL 98
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 342-442 1.45e-04

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: 43.85  E-value: 1.45e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  342 KSATPVLEVELIGDKLRTKPQNPSDNPIWNQILTFQIQLPCLSsyIKFRVMDCSKYKCQDEIGSASLCLS---------- 411
Cdd:cd04038    20 TSSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP--LKLEVFDKDTFSKDDSMGEAEIDLEplveaakldh 97

                          90       100       110
                  ....*....|....*....|....*....|...
gi 459215035  412 -QISSTGEEIQGMYSGFLPCFG-PSFLTLRGGK 442
Cdd:cd04038    98 lRDTPGGTQIKKVLPSVENCLAsESHITWKDGK 130
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1488-1576 2.30e-04

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


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 42.58  E-value: 2.30e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1488 VRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGsRDSYYPNTLDPIFGMMYELTCNIPLEKDLeIQLFDFDLITADDEI 1567
Cdd:cd04045     3 LRLHIRKANDLKNLEGVGKIDPYVRVLVNGIVKG-RTVTISNTLNPVWDEVLYVPVTSPNQKIT-LEVMDYEKVGKDRSL 80


                  ....*....
gi 459215035 1568 GSTVIDLEN 1576
Cdd:cd04045    81 GSVEINVSD 89
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 1481-1574 2.54e-04

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


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 42.64  E-value: 2.54e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1481 DFPQMCLVrVYLIRAINLQPQDYNGLCDPYVIL-------KLGQTKLgsrdsyYPNTLDPIFGMMYelTCNIPL----EK 1549
Cdd:cd08385    12 DFQSNQLT-VGIIQAADLPAMDMGGTSDPYVKVyllpdkkKKFETKV------HRKTLNPVFNETF--TFKVPYselgNK 82

                          90       100
                  ....*....|....*....|....*
gi 459215035 1550 DLEIQLFDFDLITADDEIGSTVIDL 1574
Cdd:cd08385    83 TLVFSVYDFDRFSKHDLIGEVRVPL 107
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
 2-89 2.97e-04

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


Pssm-ID: 176045 [Multi-domain]  Cd Length: 126  Bit Score: 42.74  E-value: 2.97e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035    2 LRVVVESASiNPPLSTTPKAFVTVYFRDM-MKRTRVEEGHDPIWNETLIwhLWNQPLENDSFlKVILQDSVSKKKERFIG 80
Cdd:cd08400     6 LQLNVLEAH-KLPVKHVPHPYCVISLNEVkVARTKVREGPNPVWSEEFV--FDDLPPDVNSF-TISLSNKAKRSKDSEIA 81


                  ....*....
gi 459215035   81 LATVPLKRL 89
Cdd:cd08400    82 EVTVQLSKL 90
FerI pfam08151
FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...
 276-297 6.04e-04

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


Pssm-ID: 462377  Cd Length: 52  Bit Score: 39.45  E-value: 6.04e-04
                           10        20
                   ....*....|....*....|..
gi 459215035   276 TTSGVRGYLKVTICALGVGDQA 297
Cdd:pfam08151    6 ISAGVKGYLKVDISVLGKGDEP 27
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 346-413 1.19e-03

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: 40.63  E-value: 1.19e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  346 PVLEVELIGDKL-RTKPQNPSDNPIWNQilTFQIQLPCLS-SYIKFRVMDCSKYKCQDEIGSASLCLSQI 413
Cdd:cd04040    22 PFVKFYLNGEKVfKTKTIKKTLNPVWNE--SFEVPVPSRVrAVLKVEVYDWDRGGKDDLLGSAYIDLSDL 89
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1490-1574 1.19e-03

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


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 40.75  E-value: 1.19e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1490 VYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYypNTLDPIFGMMYelTCNIpleKD----LEIQLFDFDLITADD 1565
Cdd:cd08377     5 VKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIY--KTLNPEWNKIF--TFPI---KDihdvLEVTVYDEDKDKKPE 77


                  ....*....
gi 459215035 1566 EIGSTVIDL 1574
Cdd:cd08377    78 FLGKVAIPL 86
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1489-1572 1.23e-03

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: 40.99  E-value: 1.23e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1489 RVYLIRAINLQPQDYNGLCDPYV-ILKLGQTKlgsRDSYYPNTLDP------------IFGMMYELTCNIPLekdLEIQL 1555
Cdd:cd04017     4 RAYIYQARDLLAADKSGLSDPFArVSFLNQSQ---ETEVIKETLSPtwdqtlifdeveLYGSPEEIAQNPPL---VVVEL 77

                          90
                  ....*....|....*..
gi 459215035 1556 FDFDLITADDEIGSTVI 1572
Cdd:cd04017    78 FDQDSVGKDEFLGRSVA 94
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 366-419 1.56e-03

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 40.39  E-value: 1.56e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 459215035  366 DNPIWNQILTFQIQLPCLS--SYIKFRVMDCSKYKCQDEIGSASLCLSQISSTGEE 419
Cdd:cd04049    45 RNPEWNEKFKFTVEYPGWGgdTKLILRIMDKDNFSDDDFIGEATIHLKGLFEEGVE 100
C2 pfam00168
C2 domain;
1078-1191 1.56e-03

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 39.99  E-value: 1.56e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1078 QLFCYIYQARNLMYNQILTFQEPFIQVVFL--NHSLCTQTLRSSAAPTWSQSIIFQhllLFEDPKDTrenpplVVLELWQ 1155
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 459215035  1156 HDSRGNKILWGRsmwppvVWLGLQDWVFTPL--RWHPL 1191
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSGEGldGWYPL 104
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 1490-1581 1.72e-03

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


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 40.32  E-value: 1.72e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1490 VYLIRAINLQPQDYN-GLCDPYVILKLGQTKLGSRDSYY-PNTLDPIFGMMYELtcNIP----LEKDLEIQLFDFDLITA 1563
Cdd:cd08390    18 VSLIKARNLPPRTKDvAHCDPFVKVCLLPDERRSLQSKVkRKTQNPNFDETFVF--QVSfkelQRRTLRLSVYDVDRFSR 95

                          90
                  ....*....|....*...
gi 459215035 1564 DDEIGSTVIDLENRLLSG 1581
Cdd:cd08390    96 HCIIGHVLFPLKDLDLVK 113
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1083-1131 1.77e-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: 41.08  E-value: 1.77e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 459215035 1083 IYQARNL-------MYNQILTFQ-------EPFIQVVFLNHSLCTQTLRSSAAPTWSQSIIFQ 1131
Cdd:cd04018     6 IYRAEDLpqmdsgiMANVKKAFLgekkelvDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFP 68
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1078-1180 1.81e-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: 39.78  E-value: 1.81e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035   1078 QLFCYIYQARNLMYNQILTFQEPFIQVVFLN---HSLCTQTLRSSAAPTWSQSIIFQhlllfEDPKDTREnpplVVLELW 1154
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFE-----VPPPELAE----LEIEVY 71

                            90       100
                    ....*....|....*....|....*.
gi 459215035   1155 QHDSRGNKILWGRsmwppvVWLGLQD 1180
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSD 91
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1488-1575 1.98e-03

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 40.23  E-value: 1.98e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1488 VRVYLIRAINLQPQDY-NGLCDPYVILKLGQTKLGSRDSYYPNTLDPIFGMMYELTCNiPLEKDLEIQLFDFDLITADDE 1566
Cdd:cd04044     4 LAVTIKSARGLKGSDIiGGTVDPYVTFSISNRRELARTKVKKDTSNPVWNETKYILVN-SLTEPLNLTVYDFNDKRKDKL 82


                  ....*....
gi 459215035 1567 IGSTVIDLE 1575
Cdd:cd04044    83 IGTAEFDLS 91
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 1490-1581 2.78e-03

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 39.62  E-value: 2.78e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1490 VYLIRAINLQPQDYNGLCDPYVILKLG----QTKLGSRDSYYP--------NTLDPIFGMMYELTCNIplekdleiqlFD 1557
Cdd:cd04049     5 VLLISAKGLQDTDFLGKIDPYVIIQCRtqerKSKVAKGDGRNPewnekfkfTVEYPGWGGDTKLILRI----------MD 74

                          90       100
                  ....*....|....*....|....
gi 459215035 1558 FDLITADDEIGSTVIDLENRLLSG 1581
Cdd:cd04049    75 KDNFSDDDFIGEATIHLKGLFEEG 98
C2 pfam00168
C2 domain;
1745-1847 2.89e-03

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 39.22  E-value: 2.89e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  1745 MSDIYVKGWLFGLEEdTQKTDVHYHSLTgeATFNWRFIFTMDYLTTERacvqsqkdyiwsldptstkfparLMIQIWDND 1824
Cdd:pfam00168   21 TSDPYVKVYLLDGKQ-KKKTKVVKNTLN--PVWNETFTFSVPDPENAV-----------------------LEIEVYDYD 74

                           90       100
                   ....*....|....*....|...
gi 459215035  1825 FFSPDDFLGVLELDLSDMPLPAQ 1847
Cdd:pfam00168   75 RFGRDDFIGEVRIPLSELDSGEG 97
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 1490-1577 3.19e-03

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


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 39.87  E-value: 3.19e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1490 VYLIRAINLQPQDYNGLCDPYV---ILKLGQtKLGSRD-SYYPNTLDPIFG--MMYELTCNIPLEKDLEIQLFDFDLITA 1563
Cdd:cd00276    18 VVVLKARNLPPSDGKGLSDPYVkvsLLQGGK-KLKKKKtSVKKGTLNPVFNeaFSFDVPAEQLEEVSLVITVVDKDSVGR 96

                          90
                  ....*....|....
gi 459215035 1564 DDEIGSTVIDLENR 1577
Cdd:cd00276    97 NEVIGQVVLGPDSG 110
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 1816-1873 3.20e-03

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


Pssm-ID: 176021 [Multi-domain]  Cd Length: 136  Bit Score: 39.68  E-value: 3.20e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 459215035 1816 LMIQIWDNDFFSPDDFLGVLELDLSDmplpaqnikqcsLKMMETDSKWPFTpqKRISL 1873
Cdd:cd08375    78 LCITVFDRDFFSPDDFLGRTEIRVAD------------ILKETKESKGPIT--KRLLL 121
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 1483-1535 3.40e-03

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176011 [Multi-domain]  Cd Length: 126  Bit Score: 39.57  E-value: 3.40e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 459215035 1483 PQmCLVRVYLIRAINLQPQDYNGLCDPYVILKLGQTKLGSRDSYypNTLDPIF 1535
Cdd:cd04046     1 PQ-VVTQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSPVQK--DTLSPEF 50
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 1815-1842 3.60e-03

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


Pssm-ID: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 39.17  E-value: 3.60e-03
                          10        20
                  ....*....|....*....|....*...
gi 459215035 1815 RLMIQIWDNDFFSPDDFLGVLELDLSDM 1842
Cdd:cd04041    70 RLSCRLWDSDRFTADDRLGRVEIDLKEL 97
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1-97 3.65e-03

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


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 38.70  E-value: 3.65e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035    1 MLRVVVESASiNPPL---STTPKAFVTVYFRDMMKRTRVEEG-HDPIWNET---LIWHLWNQPLEndsfLKVIlqdsvSK 73
Cdd:cd04050     1 LLFVYLDSAK-NLPLaksTKEPSPYVELTVGKTTQKSKVKERtNNPVWEEGftfLVRNPENQELE----IEVK-----DD 70

                          90       100
                  ....*....|....*....|....
gi 459215035   74 KKERFIGLATVPLKRLAQRPKEVM 97
Cdd:cd04050    71 KTGKSLGSLTLPLSELLKEPDLTL 94
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 22-91 4.11e-03

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: 39.45  E-value: 4.11e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 459215035   22 FVTVYFRDM------MKRTRV--EEGHDPIWNETLIWHLWNQPLendSFLKVILQDSVSKKKErFIGLATVPLKRLAQ 91
Cdd:cd00275    28 YVEVEIHGLpaddsaKFKTKVvkNNGFNPVWNETFEFDVTVPEL---AFLRFVVYDEDSGDDD-FLGQACLPLDSLRQ 101
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 339-418 5.98e-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: 38.77  E-value: 5.98e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035  339 GTHKSATPVLEVELIGDKLRTKPQNPSDNPIWNQILTFQIQLPCL-SSYIKFRVMDCSKYKCQDEIGSASLCLSQISSTG 417
Cdd:cd08373    10 GLKGKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGSPDpDESLEIVVKDYEKVGRNRLIGSATVSLQDLVSEG 89


                  .
gi 459215035  418 E 418
Cdd:cd08373    90 L 90
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 1490-1572 8.95e-03

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


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 38.54  E-value: 8.95e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1490 VYLIRAINLQPQDYNGLCDPYVILKLGQ-TKLGSRD--SYYPNTLDPIFGMMYelTCNIPLEK----DLEIQLFDFDLIT 1562
Cdd:cd08402    19 VVILEAKNLKKMDVGGLSDPYVKIHLMQnGKRLKKKktTIKKRTLNPYYNESF--SFEVPFEQiqkvHLIVTVLDYDRIG 96

                          90
                  ....*....|
gi 459215035 1563 ADDEIGSTVI 1572
Cdd:cd08402    97 KNDPIGKVVL 106
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 1490-1572 9.13e-03

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


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 38.56  E-value: 9.13e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 459215035 1490 VYLIRAINLQPQDYNGLCDPYVILKL--GQTKLGSRDSYYPN-TLDPIFG--MMYELTCNIPLEKDLEIQLFDFDLITAD 1564
Cdd:cd08404    19 VVVLKARHLPKMDVSGLADPYVKVNLyyGKKRISKKKTHVKKcTLNPVFNesFVFDIPSEELEDISVEFLVLDSDRVTKN 98


                  ....*...
gi 459215035 1565 DEIGSTVI 1572
Cdd:cd08404    99 EVIGRLVL 106
 
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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