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Conserved domains on  [gi|1622857443|ref|XP_028687992|]
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fer-1-like protein 5 isoform X7 [Macaca mulatta]

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 ...
 1711-1843 2.55e-69

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: 229.09  E-value: 2.55e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1711 ELRCVIWKTANVDLVDDNLSREKTSDIYIKGWLYGLEKDMQKTDIHYHSLTGEANFNWRFIFTMDYLAAERVCVQSQKDY 1790
Cdd:cd08374      1 ELRVIVWNTRDVLNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKEH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622857443 1791 IWSLDATSMKFPARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARHAQQCSI 1843
Cdd:cd08374     81 FWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1476-1599 3.39e-58

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: 196.62  E-value: 3.39e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1476 LVRVYVVRAINLQPQDYNGLCDPYVILKLGKTELGSRDMYQPNTLDPIFGTMFELTCNIPLEKDLEIQLYDFDLFSPDDK 1555
Cdd:cd04037      1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1622857443 1556 IGTTVIDLENRLLSGFGAHCGLSKSYCQSGPFRWRDQMPPSYLL 1599
Cdd:cd04037     81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1100-1235 3.85e-57

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


:

Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 194.30  E-value: 3.85e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1100 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1179
Cdd:cd04017      1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622857443 1180 DSWGKESLWGRSMWPPVVWLDLQDRILPPLRWHPLMKElGKEEGEILASCELILQT 1235
Cdd:cd04017     81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 164-273 1.47e-42

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


:

Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 151.57  E-value: 1.47e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  164 PQHFQVRVKVFEARQLMGNNIKPVVKVSIAGQQHQTRIKMGNN-PFFNEIFFQNFHEVPAKFFDETILIQVVNSSVMRYK 242
Cdd:cd04011      1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1622857443  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLCQP 273
Cdd:cd04011     81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLTDP 111
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 5-134 1.11e-33

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: 126.60  E-value: 1.11e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443    5 VVQSAKIDPPLAPLPRPCMSIDFRDVKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDTGSQKEESFIGLAT 83
Cdd:cd08373      1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1622857443   84 VLLKPLwkqPSKVLFVKDLTLLNHSMKPTDCTVTLQVAHMSHRDIEKTGAE 134
Cdd:cd08373     80 VSLQDL---VSEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127
FerB pfam08150
FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.
 716-789 1.28e-26

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


:

Pssm-ID: 462376  Cd Length: 76  Bit Score: 104.60  E-value: 1.28e-26
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622857443  716 PQMGLPDVMIWLVAKEQRVAYAQVPAHSVLFSRAgALHSGRLCGKIQTLLLQYPEGEGQKD---VLPAHLRVCMWLG 789
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 ...
 329-468 1.57e-21

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


The actual alignment was detected with superfamily member cd04018:

Pssm-ID: 472691 [Multi-domain]  Cd Length: 151  Bit Score: 93.08  E-value: 1.57e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  329 FFIYCAEDL--------------HLKKQQS-VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSSYIKFRVL 393
Cdd:cd04018      4 FKIYRAEDLpqmdsgimanvkkaFLGEKKElVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIR 83

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622857443  394 DCHRKDCSDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGGKKApFRIQEEGARIPDSVRDGLAYRG 468
Cdd:cd04018     84 DWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGSPRE-YSLLDDHQDLNEGLGEGVAYRG 151
Ferlin_C super family cl24672
Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...
 1861-1972 2.41e-18

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: 84.05  E-value: 2.41e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1861 FSLFKKKTVTGWWP----------------------------------CQVLD--GGKWRLSGKVKMSLEILSEKEALIK 1904
Cdd:pfam16165    3 VSIFRAKRMKGWWPfiklksqedfereereakkkkkkknkrsekkpedLEFKDasGNTFLLMGKVEAEFELLTVEEAEKS 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622857443 1905 PAGRGQSEPNQyptLHPPLRPYTSFIWLRSPVQHFCSVFWKRYRFKLIAFMVISILALLLFNFIYSAP 1972
Cdd:pfam16165   83 PVGKGRKEPEP---LEKPNRPKTSFSWFVNPMKTFIFFIWRRYKKYIIALLILAILALFLFLILYTLP 147
FerA super family cl06973
FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.
 620-668 3.11e-08

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: 52.20  E-value: 3.11e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1622857443  620 WEKLLRELVEDCKRPLPCMTDQPKATNLDRKRWQLRSLLLQELAQKAKQ 668
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALK 63
DysFN super family cl02740
Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...
 807-862 7.41e-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.


The actual alignment was detected with superfamily member smart00693:

Pssm-ID: 214777  Cd Length: 62  Bit Score: 47.90  E-value: 7.41e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622857443   807 VYAETYENQAKYKD-QWGQQGLYRCPNFSDVMGNK-TLPMTDFQPPLGWHWQD-SWTVE 862
Cdd:smart00693    4 FTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDdNWSLD 62
FerI super family cl06959
FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...
 273-312 1.98e-05

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: 43.69  E-value: 1.98e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1622857443  273 PNNPGSGVTGYLKVTICALGVGDQALIDQKQLYGADDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42
 
Name Accession Description Interval E-value
C2F_Ferlin cd08374
C2 domain sixth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1711-1843 2.55e-69

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: 229.09  E-value: 2.55e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1711 ELRCVIWKTANVDLVDDNLSREKTSDIYIKGWLYGLEKDMQKTDIHYHSLTGEANFNWRFIFTMDYLAAERVCVQSQKDY 1790
Cdd:cd08374      1 ELRVIVWNTRDVLNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKEH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622857443 1791 IWSLDATSMKFPARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARHAQQCSI 1843
Cdd:cd08374     81 FWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1476-1599 3.39e-58

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: 196.62  E-value: 3.39e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1476 LVRVYVVRAINLQPQDYNGLCDPYVILKLGKTELGSRDMYQPNTLDPIFGTMFELTCNIPLEKDLEIQLYDFDLFSPDDK 1555
Cdd:cd04037      1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1622857443 1556 IGTTVIDLENRLLSGFGAHCGLSKSYCQSGPFRWRDQMPPSYLL 1599
Cdd:cd04037     81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1100-1235 3.85e-57

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


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 194.30  E-value: 3.85e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1100 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1179
Cdd:cd04017      1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622857443 1180 DSWGKESLWGRSMWPPVVWLDLQDRILPPLRWHPLMKElGKEEGEILASCELILQT 1235
Cdd:cd04017     81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 164-273 1.47e-42

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


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 151.57  E-value: 1.47e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  164 PQHFQVRVKVFEARQLMGNNIKPVVKVSIAGQQHQTRIKMGNN-PFFNEIFFQNFHEVPAKFFDETILIQVVNSSVMRYK 242
Cdd:cd04011      1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1622857443  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLCQP 273
Cdd:cd04011     81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLTDP 111
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 5-134 1.11e-33

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: 126.60  E-value: 1.11e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443    5 VVQSAKIDPPLAPLPRPCMSIDFRDVKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDTGSQKEESFIGLAT 83
Cdd:cd08373      1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1622857443   84 VLLKPLwkqPSKVLFVKDLTLLNHSMKPTDCTVTLQVAHMSHRDIEKTGAE 134
Cdd:cd08373     80 VSLQDL---VSEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127
FerB pfam08150
FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.
 716-789 1.28e-26

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


Pssm-ID: 462376  Cd Length: 76  Bit Score: 104.60  E-value: 1.28e-26
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622857443  716 PQMGLPDVMIWLVAKEQRVAYAQVPAHSVLFSRAgALHSGRLCGKIQTLLLQYPEGEGQKD---VLPAHLRVCMWLG 789
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKYPGKKAKGPagwEIPAKLRVYLWLG 76
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 329-468 1.57e-21

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


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 93.08  E-value: 1.57e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  329 FFIYCAEDL--------------HLKKQQS-VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSSYIKFRVL 393
Cdd:cd04018      4 FKIYRAEDLpqmdsgimanvkkaFLGEKKElVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIR 83

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622857443  394 DCHRKDCSDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGGKKApFRIQEEGARIPDSVRDGLAYRG 468
Cdd:cd04018     84 DWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGSPRE-YSLLDDHQDLNEGLGEGVAYRG 151
Ferlin_C pfam16165
Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...
 1861-1972 2.41e-18

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: 84.05  E-value: 2.41e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1861 FSLFKKKTVTGWWP----------------------------------CQVLD--GGKWRLSGKVKMSLEILSEKEALIK 1904
Cdd:pfam16165    3 VSIFRAKRMKGWWPfiklksqedfereereakkkkkkknkrsekkpedLEFKDasGNTFLLMGKVEAEFELLTVEEAEKS 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622857443 1905 PAGRGQSEPNQyptLHPPLRPYTSFIWLRSPVQHFCSVFWKRYRFKLIAFMVISILALLLFNFIYSAP 1972
Cdd:pfam16165   83 PVGKGRKEPEP---LEKPNRPKTSFSWFVNPMKTFIFFIWRRYKKYIIALLILAILALFLFLILYTLP 147
C2 pfam00168
C2 domain;
1475-1574 3.06e-17

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 78.90  E-value: 3.06e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1475 CLVRVYVVRAINLQPQDYNGLCDPYVILKL------GKTELgsrdmyQPNTLDPIFGTMFELTCNIPLEKDLEIQLYDFD 1548
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLldgkqkKKTKV------VKNTLNPVWNETFTFSVPDPENAVLEIEVYDYD 74

                           90       100
                   ....*....|....*....|....*.
gi 1622857443 1549 LFSPDDKIGTTVIDLENRLLSGFGAH 1574
Cdd:pfam00168   75 RFGRDDFIGEVRIPLSELDSGEGLDG 100
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1476-1570 8.52e-16

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: 74.83  E-value: 8.52e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  1476 LVRVYVVRAINLQPQDYNGLCDPYVILKLG-------KTElgsrdmYQPNTLDPIFGTMFELTCNIPLEKDLEIQLYDFD 1548
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpkekkKTK------VVKNTLNPVWNETFEFEVPPPELAELEIEVYDKD 74

                            90       100
                    ....*....|....*....|..
gi 1622857443  1549 LFSPDDKIGTTVIDLENRLLSG 1570
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLLLGG 96
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 326-414 1.43e-10

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: 59.81  E-value: 1.43e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443   326 YLQFFIYCAEDL-HLKKQQSVNPQLEVELIG---EKLRTHMQTQTDNPIWNQILTFRIQLPCLSSyIKFRVLDCHRKDCS 401
Cdd:smart00239    1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFEVPPPELAE-LEIEVYDKDRFGRD 79

                            90
                    ....*....|...
gi 1622857443   402 DEIGTASLSLNQI 414
Cdd:smart00239   80 DFIGQVTIPLSDL 92
C2 pfam00168
C2 domain;
326-426 7.35e-10

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 58.10  E-value: 7.35e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  326 YLQFFIYCAEDLHLK-KQQSVNPQLEVELIG--EKLRTHMQTQTDNPIWNQILTFRIQLPcLSSYIKFRVLDCHRKDCSD 402
Cdd:pfam00168    2 RLTVTVIEAKNLPPKdGNGTSDPYVKVYLLDgkQKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFGRDD 80

                           90       100
                   ....*....|....*....|....
gi 1622857443  403 EIGTASLSLNQISStGEEIEGVYS 426
Cdd:pfam00168   81 FIGEVRIPLSELDS-GEGLDGWYP 103
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1712-1837 8.37e-09

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: 54.80  E-value: 8.37e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  1712 LRCVIWKTANVDLVDDNlsreKTSDIYIKGWLYGLEKDMQKTDIHYHSLtgeaNFNWRFIFTMDYLAAERvcvqsqkdyi 1791
Cdd:smart00239    2 LTVKIISARNLPPKDKG----GKSDPYVKVSLDGDPKEKKKTKVVKNTL----NPVWNETFEFEVPPPEL---------- 63

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 1622857443  1792 wsldatsmkfpARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARH 1837
Cdd:smart00239   64 -----------AELEIEVYDKDRFGRDDFIGQVTIPLSDLLLGGRH 98
FerA pfam08165
FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.
 620-668 3.11e-08

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


Pssm-ID: 462389  Cd Length: 65  Bit Score: 52.20  E-value: 3.11e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1622857443  620 WEKLLRELVEDCKRPLPCMTDQPKATNLDRKRWQLRSLLLQELAQKAKQ 668
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALK 63
DysFN smart00693
Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...
 807-862 7.41e-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: 47.90  E-value: 7.41e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622857443   807 VYAETYENQAKYKD-QWGQQGLYRCPNFSDVMGNK-TLPMTDFQPPLGWHWQD-SWTVE 862
Cdd:smart00693    4 FTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDdNWSLD 62
C2 pfam00168
C2 domain;
2-89 1.01e-06

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 48.85  E-value: 1.01e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443    2 LRLVVQSAK--IDPPLAPLPRP--CMSIDFRDVKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDTGSQKEE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPyvKVYLLDGKQKKKTKVVKNTlNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|...
gi 1622857443   77 SFIGLATVLLKPL 89
Cdd:pfam00168   80 DFIGEVRIPLSEL 92
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 168-264 3.12e-06

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 47.48  E-value: 3.12e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443   168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQ---HQTRIKMGN-NPFFNEIFFqnFHEVPakFFDETILIQVVNSSVM 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPkekKKTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 1622857443   240 RYKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1477-1563 1.13e-05

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 50.91  E-value: 1.13e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1477 VRVYVVRAINLQPQDY--NGLCDPYVILKLGKTELGsRDMYQPNTLDPIFGTMFELTCNiPLEKDLEIQLYDFDLFSPDD 1554
Cdd:COG5038    438 VEVKIKSAEGLKKSDStiNGTVDPYITVTFSDRVIG-KTRVKKNTLNPVWNETFYILLN-SFTDPLNLSLYDFNSFKSDK 515


                   ....*....
gi 1622857443 1555 KIGTTVIDL 1563
Cdd:COG5038    516 VVGSTQLDL 524
C2 pfam00168
C2 domain;
168-270 1.24e-05

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 45.77  E-value: 1.24e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQH--QTRIKMGN-NPFFNEIFFqnFhEVPAkFFDETILIQVVNSSVMR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQkkKTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 1622857443  241 YKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104
C2 pfam00168
C2 domain;
1101-1214 1.71e-05

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 45.39  E-value: 1.71e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1101 QLFCYIYQARNLVSNQILTFQGPFIRVVFL--NHSQCTQTLRSSAGPTWAQTLIFQhllLYENPQDTkespplVVLELWQ 1178
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1622857443 1179 RDSWGKESLWGRsmwppvVWLDLQDRILPPL--RWHPL 1214
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSGEGldGWYPL 104
FerI pfam08151
FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...
 273-312 1.98e-05

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: 43.69  E-value: 1.98e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1622857443  273 PNNPGSGVTGYLKVTICALGVGDQALIDQKQLYGADDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 2-96 2.63e-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: 44.79  E-value: 2.63e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443     2 LRLVVQSAK--IDPPLAPLPRPCMSIDF---RDVKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDTGSQKE 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLdgdPKEKKKTKVVKNTlNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90       100
                    ....*....|....*....|.
gi 1622857443    76 ESFIGLATVLLKPLWKQPSKV 96
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGGRHE 99
C2 pfam00168
C2 domain;
1803-1839 6.24e-04

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 41.15  E-value: 6.24e-04
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1622857443 1803 ARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARHAQ 1839
Cdd:pfam00168   64 AVLEIEVYDYDRFGRDDFIGEVRIPLSELDSGEGLDG 100
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1101-1212 1.60e-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: 1.60e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  1101 QLFCYIYQARNLVSNQILTFQGPFIRVVFLN---HSQCTQTLRSSAGPTWAQTLIFqhlllYENPQDTKEspplVVLELW 1177
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEF-----EVPPPELAE----LEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 1622857443  1178 QRDSWGKESLWGRsmwppvVWLDLQDRILPPLRWH 1212
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSDLLLGGRHEK 100
 
Name Accession Description Interval E-value
C2F_Ferlin cd08374
C2 domain sixth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1711-1843 2.55e-69

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: 229.09  E-value: 2.55e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1711 ELRCVIWKTANVDLVDDNLSREKTSDIYIKGWLYGLEKDMQKTDIHYHSLTGEANFNWRFIFTMDYLAAERVCVQSQKDY 1790
Cdd:cd08374      1 ELRVIVWNTRDVLNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKEH 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622857443 1791 IWSLDATSMKFPARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARHAQQCSI 1843
Cdd:cd08374     81 FWSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1476-1599 3.39e-58

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: 196.62  E-value: 3.39e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1476 LVRVYVVRAINLQPQDYNGLCDPYVILKLGKTELGSRDMYQPNTLDPIFGTMFELTCNIPLEKDLEIQLYDFDLFSPDDK 1555
Cdd:cd04037      1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1622857443 1556 IGTTVIDLENRLLSGFGAHCGLSKSYCQSGPFRWRDQMPPSYLL 1599
Cdd:cd04037     81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1100-1235 3.85e-57

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


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 194.30  E-value: 3.85e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1100 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1179
Cdd:cd04017      1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622857443 1180 DSWGKESLWGRSMWPPVVWLDLQDRILPPLRWHPLMKElGKEEGEILASCELILQT 1235
Cdd:cd04017     81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 164-273 1.47e-42

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


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 151.57  E-value: 1.47e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  164 PQHFQVRVKVFEARQLMGNNIKPVVKVSIAGQQHQTRIKMGNN-PFFNEIFFQNFHEVPAKFFDETILIQVVNSSVMRYK 242
Cdd:cd04011      1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1622857443  243 AEIGRFQTDIGFIYHSPGHTLLRKWLGLCQP 273
Cdd:cd04011     81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLTDP 111
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 5-134 1.11e-33

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: 126.60  E-value: 1.11e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443    5 VVQSAKIDPPLAPLPRPCMSIDFRDVKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDTGSQKEESFIGLAT 83
Cdd:cd08373      1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1622857443   84 VLLKPLwkqPSKVLFVKDLTLLNHSMKPTDCTVTLQVAHMSHRDIEKTGAE 134
Cdd:cd08373     80 VSLQDL---VSEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127
FerB pfam08150
FerB (NUC096) domain; This is central domain B in proteins of the Ferlin family.
 716-789 1.28e-26

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


Pssm-ID: 462376  Cd Length: 76  Bit Score: 104.60  E-value: 1.28e-26
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622857443  716 PQMGLPDVMIWLVAKEQRVAYAQVPAHSVLFSRAgALHSGRLCGKIQTLLLQYPEGEGQKD---VLPAHLRVCMWLG 789
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSPV-EEERGKFCGKVQTLFLKYPGKKAKGPagwEIPAKLRVYLWLG 76
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 329-468 1.57e-21

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


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 93.08  E-value: 1.57e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  329 FFIYCAEDL--------------HLKKQQS-VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSSYIKFRVL 393
Cdd:cd04018      4 FKIYRAEDLpqmdsgimanvkkaFLGEKKElVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIR 83

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622857443  394 DCHRKDCSDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGGKKApFRIQEEGARIPDSVRDGLAYRG 468
Cdd:cd04018     84 DWDRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGSPRE-YSLLDDHQDLNEGLGEGVAYRG 151
Ferlin_C pfam16165
Ferlin C-terminus; This domain is found at the C-terminus of proteins belonging to the ferlin ...
 1861-1972 2.41e-18

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: 84.05  E-value: 2.41e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1861 FSLFKKKTVTGWWP----------------------------------CQVLD--GGKWRLSGKVKMSLEILSEKEALIK 1904
Cdd:pfam16165    3 VSIFRAKRMKGWWPfiklksqedfereereakkkkkkknkrsekkpedLEFKDasGNTFLLMGKVEAEFELLTVEEAEKS 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622857443 1905 PAGRGQSEPNQyptLHPPLRPYTSFIWLRSPVQHFCSVFWKRYRFKLIAFMVISILALLLFNFIYSAP 1972
Cdd:pfam16165   83 PVGKGRKEPEP---LEKPNRPKTSFSWFVNPMKTFIFFIWRRYKKYIIALLILAILALFLFLILYTLP 147
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1477-1565 1.59e-17

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: 79.80  E-value: 1.59e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1477 VRVYVVRAINLQPQDYNGLCDPYVILKLGKTELG-SRdmYQPNTLDPIFGTMFELTCNIPLEKDLEIQLYDFDLFSPDDK 1555
Cdd:cd00030      1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKFkTK--VVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSKDDF 78

                           90
                   ....*....|
gi 1622857443 1556 IGTTVIDLEN 1565
Cdd:cd00030     79 LGEVEIPLSE 88
C2 pfam00168
C2 domain;
1475-1574 3.06e-17

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 78.90  E-value: 3.06e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1475 CLVRVYVVRAINLQPQDYNGLCDPYVILKL------GKTELgsrdmyQPNTLDPIFGTMFELTCNIPLEKDLEIQLYDFD 1548
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLldgkqkKKTKV------VKNTLNPVWNETFTFSVPDPENAVLEIEVYDYD 74

                           90       100
                   ....*....|....*....|....*.
gi 1622857443 1549 LFSPDDKIGTTVIDLENRLLSGFGAH 1574
Cdd:pfam00168   75 RFGRDDFIGEVRIPLSELDSGEGLDG 100
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1476-1570 8.52e-16

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: 74.83  E-value: 8.52e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  1476 LVRVYVVRAINLQPQDYNGLCDPYVILKLG-------KTElgsrdmYQPNTLDPIFGTMFELTCNIPLEKDLEIQLYDFD 1548
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDgdpkekkKTK------VVKNTLNPVWNETFEFEVPPPELAELEIEVYDKD 74

                            90       100
                    ....*....|....*....|..
gi 1622857443  1549 LFSPDDKIGTTVIDLENRLLSG 1570
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLLLGG 96
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 1476-1570 1.33e-12

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: 66.27  E-value: 1.33e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1476 LVRVYVVRAINLQPQDYNGLCDPYVILKL---GKTELGSRDMYQpnTLDPIFGT--MFELTCNIPLEKDLEIQLYDFDLF 1550
Cdd:cd08387     17 ILNVKLIQARNLQPRDFSGTADPYCKVRLlpdRSNTKQSKIHKK--TLNPEFDEsfVFEVPPQELPKRTLEVLLYDFDQF 94

                           90       100
                   ....*....|....*....|
gi 1622857443 1551 SPDDKIGTTVIDLENRLLSG 1570
Cdd:cd08387     95 SRDECIGVVELPLAEVDLSE 114
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 1479-1570 2.94e-11

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: 62.65  E-value: 2.94e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYNGLCDPYVILKL--GKTELGSRDM-YQPNTLDPIFGTMFELTcNIP----LEKDLEIQLYDFDLFS 1551
Cdd:cd04031     20 VTVLQARDLPPRDDGSLRNPYVKVYLlpDRSEKSKRRTkTVKKTLNPEWNQTFEYS-NVRretlKERTLEVTVWDYDRDG 98

                           90
                   ....*....|....*....
gi 1622857443 1552 PDDKIGTTVIDLENRLLSG 1570
Cdd:cd04031     99 ENDFLGEVVIDLADALLDD 117
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1478-1565 5.38e-11

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


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 62.06  E-value: 5.38e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1478 RVYVVRAINLQPQD--YNGLCDPYVILKLGKTELGSRDMyqPNTLDPIFGTMFELTCNIPLEKDLEIQLYDFDLFSPDDK 1555
Cdd:cd04024      4 RVHVVEAKDLAAKDrsGKGKSDPYAILSVGAQRFKTQTI--PNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKDY 81

                           90
                   ....*....|
gi 1622857443 1556 IGTTVIDLEN 1565
Cdd:cd04024     82 LGEFDIALEE 91
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 1476-1564 6.31e-11

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: 62.34  E-value: 6.31e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1476 LVRVYVVRAINLQPQDYNGlCDPYVILKLGKTELGSRDMYqpNTLDPIFGTmfELTCNIP-LEKDLEIQLYDFDLFSPDD 1554
Cdd:cd04038      3 LLKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTRVIK--KNLNPVWNE--ELTLSVPnPMAPLKLEVFDKDTFSKDD 77

                           90
                   ....*....|
gi 1622857443 1555 KIGTTVIDLE 1564
Cdd:cd04038     78 SMGEAEIDLE 87
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 326-414 1.43e-10

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: 59.81  E-value: 1.43e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443   326 YLQFFIYCAEDL-HLKKQQSVNPQLEVELIG---EKLRTHMQTQTDNPIWNQILTFRIQLPCLSSyIKFRVLDCHRKDCS 401
Cdd:smart00239    1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFEVPPPELAE-LEIEVYDKDRFGRD 79

                            90
                    ....*....|...
gi 1622857443   402 DEIGTASLSLNQI 414
Cdd:smart00239   80 DFIGQVTIPLSDL 92
C2 pfam00168
C2 domain;
326-426 7.35e-10

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 58.10  E-value: 7.35e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  326 YLQFFIYCAEDLHLK-KQQSVNPQLEVELIG--EKLRTHMQTQTDNPIWNQILTFRIQLPcLSSYIKFRVLDCHRKDCSD 402
Cdd:pfam00168    2 RLTVTVIEAKNLPPKdGNGTSDPYVKVYLLDgkQKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFGRDD 80

                           90       100
                   ....*....|....*....|....
gi 1622857443  403 EIGTASLSLNQISStGEEIEGVYS 426
Cdd:pfam00168   81 FIGEVRIPLSELDS-GEGLDGWYP 103
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 327-426 1.72e-09

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: 56.69  E-value: 1.72e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  327 LQFFIYCAEDLHLKKQQ-SVNPQLEVELIGE-KLRTHMQTQTDNPIWNQILTFRIqLPCLSSYIKFRVLDCHRKDCSDEI 404
Cdd:cd00030      1 LRVTVIEARNLPAKDLNgKSDPYVKVSLGGKqKFKTKVVKNTLNPVWNETFEFPV-LDPESDTLTVEVWDKDRFSKDDFL 79

                           90       100
                   ....*....|....*....|..
gi 1622857443  405 GTASLSLNQISSTGEEIEGVYS 426
Cdd:cd00030     80 GEVEIPLSELLDSGKEGELWLP 101
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1476-1565 4.87e-09

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


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 56.11  E-value: 4.87e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1476 LVRVYVVRAINLQPQDYNGLCDPYVILKLGKTELGSRDMYQpnTLDPIFGTMFELtcNIPLEKD--LEIQLYDFDLFSPD 1553
Cdd:cd08376      1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSK--TLNPQWLEQFDL--HLFDDQSqiLEIEVWDKDTGKKD 76

                           90
                   ....*....|..
gi 1622857443 1554 DKIGTTVIDLEN 1565
Cdd:cd08376     77 EFIGRCEIDLSA 88
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1712-1837 8.37e-09

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: 54.80  E-value: 8.37e-09
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  1712 LRCVIWKTANVDLVDDNlsreKTSDIYIKGWLYGLEKDMQKTDIHYHSLtgeaNFNWRFIFTMDYLAAERvcvqsqkdyi 1791
Cdd:smart00239    2 LTVKIISARNLPPKDKG----GKSDPYVKVSLDGDPKEKKKTKVVKNTL----NPVWNETFEFEVPPPEL---------- 63

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*.
gi 1622857443  1792 wsldatsmkfpARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARH 1837
Cdd:smart00239   64 -----------AELEIEVYDKDRFGRDDFIGQVTIPLSDLLLGGRH 98
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1477-1563 1.00e-08

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: 54.88  E-value: 1.00e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1477 VRVYVVRAINLQPQDYNGLCDPYVILKLG-----KTELGSRdmyqpnTLDPIFGTMFELTCNIPLEKDLEIQLYDFDLFS 1551
Cdd:cd04040      1 LTVDVISAENLPSADRNGKSDPFVKFYLNgekvfKTKTIKK------TLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGG 74

                           90
                   ....*....|..
gi 1622857443 1552 PDDKIGTTVIDL 1563
Cdd:cd04040     75 KDDLLGSAYIDL 86
FerA pfam08165
FerA (NUC095) domain; This is central domain A in proteins of the Ferlin family.
 620-668 3.11e-08

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


Pssm-ID: 462389  Cd Length: 65  Bit Score: 52.20  E-value: 3.11e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1622857443  620 WEKLLRELVEDCKRPLPCMTDQPKATNLDRKRWQLRSLLLQELAQKAKQ 668
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALK 63
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 1477-1561 1.50e-07

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: 52.39  E-value: 1.50e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1477 VRVYVVRAINLQPQDYNGLCDPYVILKLGKTELGSRDMyqPNTLDPIFGTMFELTCnipleKDLE-----IQLYDFDLFS 1551
Cdd:cd08375     17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVV--SDTLNPKWNSSMQFFV-----KDLEqdvlcITVFDRDFFS 89

                           90
                   ....*....|
gi 1622857443 1552 PDDKIGTTVI 1561
Cdd:cd08375     90 PDDFLGRTEI 99
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 1478-1565 1.83e-07

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: 51.85  E-value: 1.83e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1478 RVYVVRAINLQPQDYNGLCDPYVILKLGKTELGS-----RDMYQPNTLDPIFGTMFELtcNIPLEKDLE------IQLYD 1546
Cdd:cd04009     19 RVEILNARNLLPLDSNGSSDPFVKVELLPRHLFPdvptpKTQVKKKTLFPLFDESFEF--NVPPEQCSVegalllFTVKD 96

                           90
                   ....*....|....*....
gi 1622857443 1547 FDLFSPDDKIGTTVIDLEN 1565
Cdd:cd04009     97 YDLLGSNDFEGEAFLPLND 115
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 1476-1563 1.83e-07

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: 51.49  E-value: 1.83e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1476 LVRVYVVRAINLQPQDYN-GLCDPYVILKLGKTelgSRDMYQPNT----LDPIFgtmfELTC-------NIPLEKDLEIQ 1543
Cdd:cd04041      2 VLVVTIHRATDLPKADFGtGSSDPYVTASFAKF---GKPLYSTRIirkdLNPVW----EETWfvlvtpdEVKAGERLSCR 74

                           90       100
                   ....*....|....*....|
gi 1622857443 1544 LYDFDLFSPDDKIGTTVIDL 1563
Cdd:cd04041     75 LWDSDRFTADDRLGRVEIDL 94
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 331-423 4.23e-07

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


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 50.62  E-value: 4.23e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  331 IYCAEDLHLKKQ---QSVNPQLEVELIGEKL--RTHMQTQT-----DNPIWNQILTFRIQLPCLsSYIKFRVLDcHRKDC 400
Cdd:cd00275      8 IISGQQLPKPKGdkgSIVDPYVEVEIHGLPAddSAKFKTKVvknngFNPVWNETFEFDVTVPEL-AFLRFVVYD-EDSGD 85

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1622857443  401 SDEIGTASLSLNQI----------SSTGEEIEG 423
Cdd:cd00275     86 DDFLGQACLPLDSLrqgyrhvpllDSKGEPLEL 118
DysFN smart00693
Dysferlin domain, N-terminal region; Domain of unknown function present in yeast peroxisomal ...
 807-862 7.41e-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: 47.90  E-value: 7.41e-07
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*....
gi 1622857443   807 VYAETYENQAKYKD-QWGQQGLYRCPNFSDVMGNK-TLPMTDFQPPLGWHWQD-SWTVE 862
Cdd:smart00693    4 FTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDdNWSLD 62
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 1470-1563 8.97e-07

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: 49.57  E-value: 8.97e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1470 DFPQPCLVrVYVVRAINLQPQDYNGLCDPYVILKLgktelgSRDM---YQP----NTLDPIFGTMFelTCNIPL----EK 1538
Cdd:cd08385     12 DFQSNQLT-VGIIQAADLPAMDMGGTSDPYVKVYL------LPDKkkkFETkvhrKTLNPVFNETF--TFKVPYselgNK 82

                           90       100
                   ....*....|....*....|....*
gi 1622857443 1539 DLEIQLYDFDLFSPDDKIGTTVIDL 1563
Cdd:cd08385     83 TLVFSVYDFDRFSKHDLIGEVRVPL 107
C2 pfam00168
C2 domain;
2-89 1.01e-06

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 48.85  E-value: 1.01e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443    2 LRLVVQSAK--IDPPLAPLPRP--CMSIDFRDVKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDTGSQKEE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPyvKVYLLDGKQKKKTKVVKNTlNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|...
gi 1622857443   77 SFIGLATVLLKPL 89
Cdd:pfam00168   80 DFIGEVRIPLSEL 92
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 1479-1557 2.58e-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: 2.58e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYNGLCDPYVILKL---GKTELGSRDMYQPNTLDPIFGTMFELtcNIPLEK----DLEIQLYDFDLFS 1551
Cdd:cd08405     19 VNIIKARNLKAMDINGTSDPYVKVWLmykDKRVEKKKTVIKKRTLNPVFNESFIF--NIPLERlretTLIITVMDKDRLS 96


                   ....*.
gi 1622857443 1552 PDDKIG 1557
Cdd:cd08405     97 RNDLIG 102
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 169-270 2.72e-06

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


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 47.83  E-value: 2.72e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  169 VRVKVFEARQL----MGNNIKPVVKVSIAG-QQHQTRIKMGN-NPFFNEIFfqNFHEVPAKffDETILIQVVNSSVMRYK 242
Cdd:cd00030      1 LRVTVIEARNLpakdLNGKSDPYVKVSLGGkQKFKTKVVKNTlNPVWNETF--EFPVLDPE--SDTLTVEVWDKDRFSKD 76

                           90       100
                   ....*....|....*....|....*...
gi 1622857443  243 AEIGRFQTDIGFIYHSPGHTllRKWLGL 270
Cdd:cd00030     77 DFLGEVEIPLSELLDSGKEG--ELWLPL 102
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1475-1571 2.81e-06

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: 48.44  E-value: 2.81e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1475 CLVRVYVVRAINLQPQDYN------GLCDPYVILKLGKTELGSRDMyqPNTLDPIFGTMFELTCNIPLEKDLEIQLYDFD 1548
Cdd:cd08391      1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRVGAQTFKSKVI--KENLNPKWNEVYEAVVDEVPGQELEIELFDED 78

                           90       100
                   ....*....|....*....|...
gi 1622857443 1549 LfSPDDKIGTTVIDLENRLLSGF 1571
Cdd:cd08391     79 P-DKDDFLGRLSIDLGSVEKKGF 100
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 168-264 3.12e-06

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 47.48  E-value: 3.12e-06
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443   168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQ---HQTRIKMGN-NPFFNEIFFqnFHEVPakFFDETILIQVVNSSVM 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPkekKKTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 1622857443   240 RYKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1479-1565 4.27e-06

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: 47.66  E-value: 4.27e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYNGLCDPYVILKLGKTELGSRDMY---QPNTLDPIFG---TMFELTCNIPLEKDLEIQLYDFDLFSp 1552
Cdd:cd04035     19 CTIIRAKGLKAMDANGLSDPYVKLNLLPGASKATKLRtktVHKTRNPEFNetlTYYGITEEDIQRKTLRLLVLDEDRFG- 97

                           90
                   ....*....|...
gi 1622857443 1553 DDKIGTTVIDLEN 1565
Cdd:cd04035     98 NDFLGETRIPLKK 110
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1477-1564 8.12e-06

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: 47.16  E-value: 8.12e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1477 VRVYVVRAINLQPQDY-NGLCDPYVILKLGKTELGSRDMYQPNTLDPIFGTMFELTCNiPLEKDLEIQLYDFDLFSPDDK 1555
Cdd:cd04044      4 LAVTIKSARGLKGSDIiGGTVDPYVTFSISNRRELARTKVKKDTSNPVWNETKYILVN-SLTEPLNLTVYDFNDKRKDKL 82


                   ....*....
gi 1622857443 1556 IGTTVIDLE 1564
Cdd:cd04044     83 IGTAEFDLS 91
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 1476-1581 8.21e-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: 47.35  E-value: 8.21e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1476 LVRVYVVRAINLQPQDYNGLCDPYVILKLGKT-ELGSRDMYQPNT----LDPIFGTMFELTCNiPLEKDLEIQLYDFDLF 1550
Cdd:cd04033      1 ILRVKVLAGIDLAKKDIFGASDPYVKISLYDPdGNGEIDSVQTKTikktLNPKWNEEFFFRVN-PREHRLLFEVFDENRL 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1622857443 1551 SPDDKIGTTVIDLENRLLSGFGAHCGLS-KSY 1581
Cdd:cd04033     80 TRDDFLGQVEVPLNNLPTETPGNERRYTfKDY 111
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1479-1557 1.03e-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: 46.96  E-value: 1.03e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYNGLCDPYVILKLgktelgSRDMYQPN---------TLDPIFGTMFELTCNIP-LEKD-LEIQLYDF 1547
Cdd:cd08384     17 VGIIRCVNLAAMDANGYSDPFVKLYL------KPDAGKKSkhktqvkkkTLNPEFNEEFFYDIKHSdLAKKtLEITVWDK 90

                           90
                   ....*....|
gi 1622857443 1548 DLFSPDDKIG 1557
Cdd:cd08384     91 DIGKSNDYIG 100
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1477-1563 1.13e-05

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 50.91  E-value: 1.13e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1477 VRVYVVRAINLQPQDY--NGLCDPYVILKLGKTELGsRDMYQPNTLDPIFGTMFELTCNiPLEKDLEIQLYDFDLFSPDD 1554
Cdd:COG5038    438 VEVKIKSAEGLKKSDStiNGTVDPYITVTFSDRVIG-KTRVKKNTLNPVWNETFYILLN-SFTDPLNLSLYDFNSFKSDK 515


                   ....*....
gi 1622857443 1555 KIGTTVIDL 1563
Cdd:COG5038    516 VVGSTQLDL 524
C2 pfam00168
C2 domain;
168-270 1.24e-05

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 45.77  E-value: 1.24e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQH--QTRIKMGN-NPFFNEIFFqnFhEVPAkFFDETILIQVVNSSVMR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQkkKTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 1622857443  241 YKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 1475-1570 1.24e-05

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


Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 46.79  E-value: 1.24e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1475 CLVRVYVVRAINLQPQDYNGLCDPYVILKLGKTELGSRDMYQpnTLDPIFGTMFELTCNIPLEKdLEIQLY--DFDLFS- 1551
Cdd:cd04027      1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQ--NLNPVWNEKFHFECHNSSDR-IKVRVWdeDDDIKSr 77

                           90       100
                   ....*....|....*....|....*..
gi 1622857443 1552 --------PDDKIGTTVIDLenRLLSG 1570
Cdd:cd04027     78 lkqkftreSDDFLGQTIIEV--RTLSG 102
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 1479-1570 1.65e-05

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: 46.10  E-value: 1.65e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYN-GLCDPYVILKLGKTELGSRDMY-QPNTLDPIFGTMFELtcNIP----LEKDLEIQLYDFDLFSP 1552
Cdd:cd08390     18 VSLIKARNLPPRTKDvAHCDPFVKVCLLPDERRSLQSKvKRKTQNPNFDETFVF--QVSfkelQRRTLRLSVYDVDRFSR 95

                           90
                   ....*....|....*...
gi 1622857443 1553 DDKIGTTVIDLENRLLSG 1570
Cdd:cd08390     96 HCIIGHVLFPLKDLDLVK 113
C2 pfam00168
C2 domain;
1101-1214 1.71e-05

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 45.39  E-value: 1.71e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1101 QLFCYIYQARNLVSNQILTFQGPFIRVVFL--NHSQCTQTLRSSAGPTWAQTLIFQhllLYENPQDTkespplVVLELWQ 1178
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1622857443 1179 RDSWGKESLWGRsmwppvVWLDLQDRILPPL--RWHPL 1214
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSGEGldGWYPL 104
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 1479-1557 1.74e-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: 46.10  E-value: 1.74e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYNGLCDPYVILKLG---KTELGSRDMYQPNTLDPIFGTMFELTCNiPLEKD--LEIQLYDFDLFSPD 1553
Cdd:cd04026     17 VEVREAKNLIPMDPNGLSDPYVKLKLIpdpKNETKQKTKTIKKTLNPVWNETFTFDLK-PADKDrrLSIEVWDWDRTTRN 95


                   ....
gi 1622857443 1554 DKIG 1557
Cdd:cd04026     96 DFMG 99
FerI pfam08151
FerI (NUC094) domain; This domain is present in proteins of the Ferlin family. It is often ...
 273-312 1.98e-05

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: 43.69  E-value: 1.98e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1622857443  273 PNNPGSGVTGYLKVTICALGVGDQALIDQKQLYGADDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 2-96 2.63e-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: 44.79  E-value: 2.63e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443     2 LRLVVQSAK--IDPPLAPLPRPCMSIDF---RDVKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDTGSQKE 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLdgdPKEKKKTKVVKNTlNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90       100
                    ....*....|....*....|.
gi 1622857443    76 ESFIGLATVLLKPLWKQPSKV 96
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGGRHE 99
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1733-1830 4.08e-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: 4.08e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1733 KTSDIYIKGWLYGLEKdmQKTDIHYHSLtgeaNFNWRFIFTMDYLAAERvcvqsqkdyiwsldatsmkfpARLIIQVWDN 1812
Cdd:cd00030     18 GKSDPYVKVSLGGKQK--FKTKVVKNTL----NPVWNETFEFPVLDPES---------------------DTLTVEVWDK 70

                           90
                   ....*....|....*...
gi 1622857443 1813 DIFSPDDFLGVLELDLSD 1830
Cdd:cd00030     71 DRFSKDDFLGEVEIPLSE 88
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
1453-1567 5.07e-05

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


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 48.60  E-value: 5.07e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1453 PDAPKPPLQFLAWPEREDFPQPCLVR------VYVVRAINLQPQDYNGLCDPYVILKLGKTELgSRDMYQPNTLDPIFGT 1526
Cdd:COG5038   1012 PGSAKVLVQVSYTPVPVKLPPVEMVEnsgyltIMLRSGENLPSSDENGYSDPFVKLFLNEKSV-YKTKVVKKTLNPVWNE 1090

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1622857443 1527 MFELTCNIPLEKDLEIQLYDFDLFSPDDKIGTTVIDLENRL 1567
Cdd:COG5038   1091 EFTIEVLNRVKDVLTINVNDWDSGEKNDLLGTAEIDLSKLE 1131
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1476-1565 8.47e-05

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


Pssm-ID: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 44.19  E-value: 8.47e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1476 LVRVYVVRAINLQPQDYNGLCDPYVILKL-GKTELGSRDMYQpnTLDPIFGTMFeltcNIPLE---KDLEIQLYDFDLFS 1551
Cdd:cd04042      1 QLDIHLKEGRNLAARDRGGTSDPYVKFKYgGKTVYKSKTIYK--NLNPVWDEKF----TLPIEdvtQPLYIKVFDYDRGL 74

                           90
                   ....*....|....
gi 1622857443 1552 PDDKIGTTVIDLEN 1565
Cdd:cd04042     75 TDDFMGSAFVDLST 88
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 1479-1566 9.66e-05

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


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 44.11  E-value: 9.66e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYNGLCDPYV---ILKLG------KTELgsrdmyQPNTLDPIFG-TM-FELTCNIPLEKDLEIQLYDF 1547
Cdd:cd00276     18 VVVLKARNLPPSDGKGLSDPYVkvsLLQGGkklkkkKTSV------KKGTLNPVFNeAFsFDVPAEQLEEVSLVITVVDK 91

                           90
                   ....*....|....*....
gi 1622857443 1548 DLFSPDDKIGTTVIDLENR 1566
Cdd:cd00276     92 DSVGRNEVIGQVVLGPDSG 110
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1102-1214 1.29e-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: 1.29e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1102 LFCYIYQARNLVSNQILTFQGPFIRVVFLN-HSQCTQTLRSSAGPTWAQTLIFQHlllyenpqdTKESPPLVVLELWQRD 1180
Cdd:cd00030      1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGkQKFKTKVVKNTLNPVWNETFEFPV---------LDPESDTLTVEVWDKD 71

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1622857443 1181 SWGKESLWGRSMWPPVvwlDLQDRILPPLRWHPL 1214
Cdd:cd00030     72 RFSKDDFLGEVEIPLS---ELLDSGKEGELWLPL 102
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 1477-1569 1.47e-04

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 43.06  E-value: 1.47e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1477 VRVYVVRAINLQPQD-YNGLCDPYVILKLGKTELGSrDMYqPNTLDPIFGT---MFELTCNIPLEKDLEIQLYDFDLFSP 1552
Cdd:cd08688      1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFGSTTYKT-DVV-KKSLNPVWNSewfRFEVDDEELQDEPLQIRVMDHDTYSA 78

                           90
                   ....*....|....*..
gi 1622857443 1553 DDKIGTTVIDLeNRLLS 1569
Cdd:cd08688     79 NDAIGKVYIDL-NPLLL 94
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 31-102 1.53e-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: 1.53e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1622857443   31 KKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDTGSQKEESFIGLATVLLKPLWKQPSKVLFVKDL 102
Cdd:cd00030     33 KFKTKVVKNTlNPVWNETFEFPV---LDPESDTLTVEVWDKDRFSKDDFLGEVEIPLSELLDSGKEGELWLPL 102
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 327-414 2.01e-04

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


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 43.03  E-value: 2.01e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  327 LQFFIYCAEDLHLKKQQSVNPQLEVELIGEKLR-THMQTQTDNPIWNQILTFRIQlPclSSYIKFRVLDCH--RKDCSde 403
Cdd:cd04021      4 LQITVESAKLKSNSKSFKPDPYVEVTVDGQPPKkTEVSKKTSNPKWNEHFTVLVT-P--QSTLEFKVWSHHtlKADVL-- 78

                           90
                   ....*....|.
gi 1622857443  404 IGTASLSLNQI 414
Cdd:cd04021     79 LGEASLDLSDI 89
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 347-430 2.04e-04

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


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 42.56  E-value: 2.04e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  347 PQLEVELIGEKL-RTHMQTQTDNPIWNQilTFRIQLPCLS-SYIKFRVLDCHRKDCSDEIGTASLSLNQISS-------- 416
Cdd:cd04040     22 PFVKFYLNGEKVfKTKTIKKTLNPVWNE--SFEVPVPSRVrAVLKVEVYDWDRGGKDDLLGSAYIDLSDLEPeetteltl 99

                           90
                   ....*....|....*.
gi 1622857443  417 --TGEEIEGVYSGFLP 430
Cdd:cd04040    100 plDGQGGGKLGAVFLP 115
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 1474-1557 2.79e-04

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: 42.65  E-value: 2.79e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1474 PCLV-RVYVVRAINLQPQDYNGLCDPYVILKLGKTELGSRdmYQPNTLDPIFGTMFeltcnIPLEKDLE----IQLYDFD 1548
Cdd:cd04046      1 PQVVtQVHVHSAEGLSKQDSGGGADPYVIIKCEGESVRSP--VQKDTLSPEFDTQA-----IFYRKKPRspikIQVWNSN 73


                   ....*....
gi 1622857443 1549 LFSpDDKIG 1557
Cdd:cd04046     74 LLC-DEFLG 81
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 171-248 2.89e-04

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


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 42.96  E-value: 2.89e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  171 VKVFEARQLM----GNNIKPVVKVSIAGQ-----QHQTRIKMGN-NPFFNEIFfqNFhEVPAKFFDE-TILIQVVNSSVM 239
Cdd:cd00276     18 VVVLKARNLPpsdgKGLSDPYVKVSLLQGgkklkKKKTSVKKGTlNPVFNEAF--SF-DVPAEQLEEvSLVITVVDKDSV 94


                   ....*....
gi 1622857443  240 RYKAEIGRF 248
Cdd:cd00276     95 GRNEVIGQV 103
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 346-422 3.63e-04

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


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 42.57  E-value: 3.63e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  346 NPQLEVELI--GEKL---RTHMQTQTDNPIWNQILTFRI---QLPCLSsyIKFRVLDCHRKDCSDEIGTASLSLNqisST 417
Cdd:cd00276     36 DPYVKVSLLqgGKKLkkkKTSVKKGTLNPVFNEAFSFDVpaeQLEEVS--LVITVVDKDSVGRNEVIGQVVLGPD---SG 110


                   ....*
gi 1622857443  418 GEEIE 422
Cdd:cd00276    111 GEELE 115
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 330-414 3.85e-04

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


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 41.78  E-value: 3.85e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  330 FIYCAEDLHLKKQQS-VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPcLSSYIKFRVLDcHRKDCSdeIGTAS 408
Cdd:cd04050      5 YLDSAKNLPLAKSTKePSPYVELTVGKTTQKSKVKERTNNPVWEEGFTFLVRNP-ENQELEIEVKD-DKTGKS--LGSLT 80


                   ....*.
gi 1622857443  409 LSLNQI 414
Cdd:cd04050     81 LPLSEL 86
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1479-1563 5.31e-04

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: 41.52  E-value: 5.31e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYNGLCDPYVILKLGKTELGSRDMYQpnTLDPIFGTMFelTCNIpleKD----LEIQLYDFDLFSPDD 1554
Cdd:cd08377      5 VKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYK--TLNPEWNKIF--TFPI---KDihdvLEVTVYDEDKDKKPE 77


                   ....*....
gi 1622857443 1555 KIGTTVIDL 1563
Cdd:cd08377     78 FLGKVAIPL 86
C2 pfam00168
C2 domain;
1803-1839 6.24e-04

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 41.15  E-value: 6.24e-04
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1622857443 1803 ARLIIQVWDNDIFSPDDFLGVLELDLSDMPLPARHAQ 1839
Cdd:pfam00168   64 AVLEIEVYDYDRFGRDDFIGEVRIPLSELDSGEGLDG 100
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 1479-1561 1.18e-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: 41.23  E-value: 1.18e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYNGLCDPYVILKL---GKTELGSRDMYQPNTLDPIFGTMFelTCNIPLEK----DLEIQLYDFDLFS 1551
Cdd:cd08402     19 VVILEAKNLKKMDVGGLSDPYVKIHLmqnGKRLKKKKTTIKKRTLNPYYNESF--SFEVPFEQiqkvHLIVTVLDYDRIG 96

                           90
                   ....*....|
gi 1622857443 1552 PDDKIGTTVI 1561
Cdd:cd08402     97 KNDPIGKVVL 106
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 1479-1570 1.29e-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: 40.78  E-value: 1.29e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYNGLCDPYVILKLGKTELGS---RDMYQpntlDPIFGTMFELTCNIPLEK---DLEIQLYDFDLFSP 1552
Cdd:cd04049      5 VLLISAKGLQDTDFLGKIDPYVIIQCRTQERKSkvaKGDGR----NPEWNEKFKFTVEYPGWGgdtKLILRIMDKDNFSD 80

                           90
                   ....*....|....*...
gi 1622857443 1553 DDKIGTTVIDLENRLLSG 1570
Cdd:cd04049     81 DDFIGEATIHLKGLFEEG 98
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1101-1212 1.60e-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: 1.60e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  1101 QLFCYIYQARNLVSNQILTFQGPFIRVVFLN---HSQCTQTLRSSAGPTWAQTLIFqhlllYENPQDTKEspplVVLELW 1177
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEF-----EVPPPELAE----LEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 1622857443  1178 QRDSWGKESLWGRsmwppvVWLDLQDRILPPLRWH 1212
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSDLLLGGRHEK 100
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 29-90 1.90e-03

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: 40.31  E-value: 1.90e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443   29 DVKKRTRVVEG-NDPVWNETLIWHLWNRPLENDSFLQVTLQDTGSQKEESFIG-----LATVLL--KPLW 90
Cdd:cd04031     52 KSKRRTKTVKKtLNPEWNQTFEYSNVRRETLKERTLEVTVWDYDRDGENDFLGevvidLADALLddEPHW 121
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 344-443 1.95e-03

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


Pssm-ID: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 40.77  E-value: 1.95e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443  344 SVNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSsyIKFRVLDCHRKDCSDEIGTASLSL-----------N 412
Cdd:cd04038     21 SSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVPNPMAP--LKLEVFDKDTFSKDDSMGEAEIDLeplveaakldhL 98

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1622857443  413 QISSTGEEIEGVYSGFLPCFG-PSFLTLHGGK 443
Cdd:cd04038     99 RDTPGGTQIKKVLPSVENCLAsESHITWKDGK 130
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 365-420 1.97e-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: 40.01  E-value: 1.97e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1622857443  365 QTDNPIWNQILTFRIQLPCLS--SYIKFRVLDCHRKDCSDEIGTASLSLNQISSTGEE 420
Cdd:cd04049     43 DGRNPEWNEKFKFTVEYPGWGgdTKLILRIMDKDNFSDDDFIGEATIHLKGLFEEGVE 100
C2_Intersectin cd08375
C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...
 1784-1831 2.55e-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: 40.06  E-value: 2.55e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1622857443 1784 VQSQKDYIWSldaTSMKFPAR------LIIQVWDNDIFSPDDFLGVLELDLSDM 1831
Cdd:cd08375     54 VSDTLNPKWN---SSMQFFVKdleqdvLCITVFDRDFFSPDDFLGRTEIRVADI 104
C2_Ras_p21A1 cd08400
C2 domain present in RAS p21 protein activator 1 (RasA1); RasA1 is a GAP1 (GTPase activating ...
 2-89 2.78e-03

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


Pssm-ID: 176045 [Multi-domain]  Cd Length: 126  Bit Score: 39.66  E-value: 2.78e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443    2 LRLVVQSA-KIdpPLAPLPRPCMSIDFRDVK-KRTRVVEGNDPVWNETLIwhLWNRPLENDSFlQVTLQDTGSQKEESFI 79
Cdd:cd08400      6 LQLNVLEAhKL--PVKHVPHPYCVISLNEVKvARTKVREGPNPVWSEEFV--FDDLPPDVNSF-TISLSNKAKRSKDSEI 80

                           90
                   ....*....|
gi 1622857443   80 GLATVLLKPL 89
Cdd:cd08400     81 AEVTVQLSKL 90
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 1102-1222 4.47e-03

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


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 39.01  E-value: 4.47e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1102 LFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQhllLYENPqdtkesPPLVVLELWQRDS 1181
Cdd:cd04025      2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFE---LMEGA------DSPLSVEVWDWDL 72

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1622857443 1182 WGKESLWGRsmwppvVWLDLQ--DRILPPLRWHPLMKELGKEE 1222
Cdd:cd04025     73 VSKNDFLGK------VVFSIQtlQQAKQEEGWFRLLPDPRAEE 109
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 1479-1561 5.27e-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: 39.33  E-value: 5.27e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1479 VYVVRAINLQPQDYNGLCDPYV---ILKLGKTELGSRDMYQPNTLDPIFGTMF--ELTCNIPLEKDLEIQLYDFDLFSPD 1553
Cdd:cd08404     19 VVVLKARHLPKMDVSGLADPYVkvnLYYGKKRISKKKTHVKKCTLNPVFNESFvfDIPSEELEDISVEFLVLDSDRVTKN 98


                   ....*...
gi 1622857443 1554 DKIGTTVI 1561
Cdd:cd08404     99 EVIGRLVL 106
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 1481-1572 5.42e-03

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


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 38.78  E-value: 5.42e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1481 VVRAINLQPQDYNGLCDPYVIL--KLGKTELGS-RDMYqpNTLDPIFGTMFELTCNIPLEKDLEIQLYDFDLFSPDDKIG 1557
Cdd:cd04043      7 IVRAENLKADSSNGLSDPYVTLvdTNGKRRIAKtRTIY--DTLNPRWDEEFELEVPAGEPLWISATVWDRSFVGKHDLCG 84

                           90
                   ....*....|....*
gi 1622857443 1558 TTVIDLENRLLSGFG 1572
Cdd:cd04043     85 RASLKLDPKRFGDDG 99
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 345-411 7.47e-03

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


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 38.33  E-value: 7.47e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622857443  345 VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLP---CLSSYIKFRVLDcHRKDCSDE-IGTASLSL 411
Cdd:cd04011     21 IDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHESpdeLFDKIIKISVYD-SRSLRSDTlIGSFKLDV 90
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 346-379 7.69e-03

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


Pssm-ID: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 38.43  E-value: 7.69e-03
                           10        20        30
                   ....*....|....*....|....*....|....
gi 1622857443  346 NPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRI 379
Cdd:cd08377     23 DPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPI 56
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1477-1565 8.54e-03

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: 38.34  E-value: 8.54e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622857443 1477 VRVYVVRAINLQPQDYNGLCDPYVILKLGKTELGsRDMYQPNTLDPIFGTMFELTCNIPLEKDLeIQLYDFDLFSPDDKI 1556
Cdd:cd04045      3 LRLHIRKANDLKNLEGVGKIDPYVRVLVNGIVKG-RTVTISNTLNPVWDEVLYVPVTSPNQKIT-LEVMDYEKVGKDRSL 80


                   ....*....
gi 1622857443 1557 GTTVIDLEN 1565
Cdd:cd04045     81 GSVEINVSD 89
 
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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