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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299 1076 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1155
Cdd:cd04017      1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462578299 1156 DFWGKESLWGRSVWPPMVWLDLQDRILPPMRWHPLVKElGKEEGEILASCELILQT 1211
Cdd:cd04017     81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299    5 VVQSAKIDPPLAPLPRPCMSIDFRDIKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDMGSQKKERFIGLAT 83
Cdd:cd08373      1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2462578299   84 VLLKPLLkqpSEVLFVKDLTLLNHSMKPTDCTVTLQVAHMSNQDIEKTGAE 134
Cdd:cd08373     80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  331 IYCAEDL----------HLKKHQS-----VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSSYIKFRVLDC 395
Cdd:cd04018      6 IYRAEDLpqmdsgimanVKKAFLGekkelVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIRDW 85

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462578299  396 RKKDCPDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGGKKApFRIQEEGACIPDSVRDGLAYRG 468
Cdd:cd04018     86 DRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGSPRE-YSLLDDHQDLNEGLGEGVAYRG 151

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2462578299  620 WEKLLRELAEDCKRPLPCMTYQPKATSLDRKRWQLRSLLLQELAQKAKQAK 670
Cdd:pfam08165   15 WLKLLDQLIEDCSKPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALKLR 65

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299 1076 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1155
Cdd:cd04017      1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462578299 1156 DFWGKESLWGRSVWPPMVWLDLQDRILPPMRWHPLVKElGKEEGEILASCELILQT 1211
Cdd:cd04017     81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299    5 VVQSAKIDPPLAPLPRPCMSIDFRDIKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDMGSQKKERFIGLAT 83
Cdd:cd08373      1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2462578299   84 VLLKPLLkqpSEVLFVKDLTLLNHSMKPTDCTVTLQVAHMSNQDIEKTGAE 134
Cdd:cd08373     80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  331 IYCAEDL----------HLKKHQS-----VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSSYIKFRVLDC 395
Cdd:cd04018      6 IYRAEDLpqmdsgimanVKKAFLGekkelVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIRDW 85

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462578299  396 RKKDCPDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGGKKApFRIQEEGACIPDSVRDGLAYRG 468
Cdd:cd04018     86 DRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGSPRE-YSLLDDHQDLNEGLGEGVAYRG 151

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  326 YLQLFIYCAEDLHLK-KHQSVNPQLEVELIG--EKLRTHMQTQTDNPIWNQILTFRIQLPcLSSYIKFRVLDCRKKDCPD 402
Cdd:pfam00168    2 RLTVTVIEAKNLPPKdGNGTSDPYVKVYLLDgkQKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFGRDD 80

                           90       100
                   ....*....|....*....|....
gi 2462578299  403 EIGTASLSLNQISStGEEIEGVYS 426
Cdd:pfam00168   81 FIGEVRIPLSELDS-GEGLDGWYP 103

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299    2 LRLVVQSAK--IDPPLAPLPRP--CMSIDFRDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKKE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPyvKVYLLDGKQKKKTKVVKNTlNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*.
gi 2462578299   77 RFIGLATVLLKPLLKQ 92
Cdd:pfam00168   80 DFIGEVRIPLSELDSG 95

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299     2 LRLVVQSAK--IDPPLAPLPRPCMSIDF---RDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKK 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLdgdPKEKKKTKVVKNTlNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90
                    ....*....|....*...
gi 2462578299    76 ERFIGLATVLLKPLLKQP 93
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGG 96

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQH--QTRIKMGN-NPFFNEIFFqnFhEVPAkFFDETILIQVVNSSAMR 240
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLLDGKQkkKTKVVKNTlNPVWNETFT--F-SVPD-PENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 2462578299  241 YKAEIGRFQTDIGFIYHSPGHTllrKWLGL 270
Cdd:pfam00168   78 RDDFIGEVRIPLSELDSGEGLD---GWYPL 104

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2462578299  273 PNNPGSGVTGYLKVTIYALGVGDQALIDQKLLYGTDDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299 1076 YQLFCYIYQARNLVSNQILTFQGPFIRVVFLNHSQCTQTLRSSAGPTWAQTLIFQHLLLYENPQDTKESPPLVVLELWQR 1155
Cdd:cd04017      1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462578299 1156 DFWGKESLWGRSVWPPMVWLDLQDRILPPMRWHPLVKElGKEEGEILASCELILQT 1211
Cdd:cd04017     81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKG-GQSAGELLAAFELIEVT 135

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299    5 VVQSAKIDPPLAPLPRPCMSIDFRDIKKRTRVVEG-NDPVWNETLIWHLWNRPlENDSFLQVTLQDMGSQKKERFIGLAT 83
Cdd:cd08373      1 LVVSLKNLPGLKGKGDRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSAT 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2462578299   84 VLLKPLLkqpSEVLFVKDLTLLNHSMKPTDCTVTLQVAHMSNQDIEKTGAE 134
Cdd:cd08373     80 VSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  331 IYCAEDL----------HLKKHQS-----VNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCLSSYIKFRVLDC 395
Cdd:cd04018      6 IYRAEDLpqmdsgimanVKKAFLGekkelVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERIKIQIRDW 85

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462578299  396 RKKDCPDEIGTASLSLNQISSTGEEiegvysGFLPCFGPSFLTLHGGKKApFRIQEEGACIPDSVRDGLAYRG 468
Cdd:cd04018     86 DRVGNDDVIGTHFIDLSKISNSGDE------GFLPTFGPSFVNLYGSPRE-YSLLDDHQDLNEGLGEGVAYRG 151

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  327 LQLFIYCAEDLHLK-KHQSVNPQLEVELIGE-KLRTHMQTQTDNPIWNQILTFRIqLPCLSSYIKFRVLDCRKKDCPDEI 404
Cdd:cd00030      1 LRVTVIEARNLPAKdLNGKSDPYVKVSLGGKqKFKTKVVKNTLNPVWNETFEFPV-LDPESDTLTVEVWDKDRFSKDDFL 79

                           90       100
                   ....*....|....*....|..
gi 2462578299  405 GTASLSLNQISSTGEEIEGVYS 426
Cdd:cd00030     80 GEVEIPLSELLDSGKEGELWLP 101

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.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462578299   780 DTAVYAEMYENQAKYKD-QWGQQGLYHCPNFSDVMGNK-TLPMTDFQPPLGWHWQD-SWTVE 838
Cdd:smart00693    1 PIRFTEEMYENQRRWLGgGWKTTLLPYRPKFSDASGGKeCLPKENLLPPPGWEWEDdNWSLD 62

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299    2 LRLVVQSAK--IDPPLAPLPRP--CMSIDFRDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKKE 76
Cdd:pfam00168    3 LTVTVIEAKnlPPKDGNGTSDPyvKVYLLDGKQKKKTKVVKNTlNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*.
gi 2462578299   77 RFIGLATVLLKPLLKQ 92
Cdd:pfam00168   80 DFIGEVRIPLSELDSG 95

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299     2 LRLVVQSAK--IDPPLAPLPRPCMSIDF---RDIKKRTRVVEGN-DPVWNETLIWHLwnrPLENDSFLQVTLQDMGSQKK 75
Cdd:smart00239    2 LTVKIISARnlPPKDKGGKSDPYVKVSLdgdPKEKKKTKVVKNTlNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90
                    ....*....|....*...
gi 2462578299    76 ERFIGLATVLLKPLLKQP 93
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGG 96

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299   168 QVRVKVFEARQLMGNNIK----PVVKVSIAGQQ---HQTRIKMGN-NPFFNEIFFqnFHEVPakFFDETILIQVVNSSAM 239
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDPkekKKTKVVKNTlNPVWNETFE--FEVPP--PELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 2462578299   240 RYKAEIGRFQTDIGFIYHSPGHTLL 264
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299 1077 QLFCYIYQARNLVSNQILTFQGPFIRVVFL--NHSQCTQTLRSSAGPTWAQTLIFQhllLYENPQDTkespplVVLELWQ 1154
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLdgKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2462578299 1155 RDFWGKESLWGRsvwppmVWLDLQDRIL--PPMRWHPL 1190
Cdd:pfam00168   73 YDRFGRDDFIGE------VRIPLSELDSgeGLDGWYPL 104

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  171 VKVFEARQLM----GNNIKPVVKVSIAGQ-----QHQTRIKMGN-NPFFNEIFfqNFhEVPAKFFDE-TILIQVVNSSAM 239
Cdd:cd00276     18 VVVLKARNLPpsdgKGLSDPYVKVSLLQGgkklkKKKTSVKKGTlNPVFNEAF--SF-DVPAEQLEEvSLVITVVDKDSV 94

                   ....*....
gi 2462578299  240 RYKAEIGRF 248
Cdd:cd00276     95 GRNEVIGQV 103

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  327 LQLFIYCAEDLHLKKHQSVNPQLEVELIGEKLR-THMQTQTDNPIWNQILTFRIQlPclSSYIKFRVLDCRKKDcPDE-I 404
Cdd:cd04021      4 LQITVESAKLKSNSKSFKPDPYVEVTVDGQPPKkTEVSKKTSNPKWNEHFTVLVT-P--QSTLEFKVWSHHTLK-ADVlL 79

                           90
                   ....*....|
gi 2462578299  405 GTASLSLNQI 414
Cdd:cd04021     80 GEASLDLSDI 89

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  334 AEDLHLKK-HQSVNPQLEVELI--GEKL---RTHMQTQTDNPIWNQILTFRI---QLPCLSsyIKFRVLDCRKKDCPDEI 404
Cdd:cd00276     23 ARNLPPSDgKGLSDPYVKVSLLqgGKKLkkkKTSVKKGTLNPVFNEAFSFDVpaeQLEEVS--LVITVVDKDSVGRNEVI 100

                           90
                   ....*....|....*...
gi 2462578299  405 GTASLSLNqisSTGEEIE 422
Cdd:cd00276    101 GQVVLGPD---SGGEELE 115

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2462578299  273 PNNPGSGVTGYLKVTIYALGVGDQALIDQKLLYGTDDTDI 312
Cdd:pfam08151    3 PDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAEDDI 42

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  347 PQLEVELIGEKL-RTHMQTQTDNPIWNQilTFRIQLPCLS-SYIKFRVLDCRKKDCPDEIGTASLSLNQISS-------- 416
Cdd:cd04040     22 PFVKFYLNGEKVfKTKTIKKTLNPVWNE--SFEVPVPSRVrAVLKVEVYDWDRGGKDDLLGSAYIDLSDLEPeetteltl 99

                           90
                   ....*....|....*.
gi 2462578299  417 --TGEEIEGVYSGFLP 430
Cdd:cd04040    100 plDGQGGGKLGAVFLP 115

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  1077 QLFCYIYQARNLVSNQILTFQGPFIRVVFLN---HSQCTQTLRSSAGPTWAQTLIFqhlllYENPQDTKEspplVVLELW 1153
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEF-----EVPPPELAE----LEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 2462578299  1154 QRDFWGKESLWGRsvwppmVWLDLQDRILPPMRWH 1188
Cdd:smart00239   72 DKDRFGRDDFIGQ------VTIPLSDLLLGGRHEK 100

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.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462578299  346 NPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLpcLSSYIKFRVLDCRKKDCPDEIGTASLSLNQISStGEE 420
Cdd:cd08377     23 DPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKD--IHDVLEVTVYDEDKDKKPEFLGKVAIPLLSIKN-GER 94

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462578299  340 KKHQSVNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRIQLPCL-SSYIKFRVLDCRKKDCPDEIGTASLSLNQISSTG 418
Cdd:cd08373     10 GLKGKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGSPDpDESLEIVVKDYEKVGRNRLIGSATVSLQDLVSEG 89

                   .
gi 2462578299  419 E 419
Cdd:cd08373     90 L 90

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2462578299  334 AEDLHLK-KHQSVNPQLEVELIGEKLRTHMQTQTDNPIWNQILTFRI 379
Cdd:cd04022      9 AQDLMPKdGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNV 55