NCBI Conserved Domain Search

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: 247.93 E-value: 9.53e-76

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  365 TLSLKIYRAEDMPQMDDAFAQTVKhiFGGTDDKKNLVDPFVEVNFAGKKVCTKIIEKNANPEWNQLIHLQVKFPSMCERI 444
Cdd:cd04018     1 RFIFKIYRAEDLPQMDSGIMANVK--KAFLGEKKELVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCERI 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  445 KLTAFDWDRLSKNDVIGTTYLNLTKIASSGGEieetpsenglpssfnvdtteaevGFLPAFGPCYINLYGSPREFTGLPD 524
Cdd:cd04018    79 KIQIRDWDRVGNDDVIGTHFIDLSKISNSGDE-----------------------GFLPTFGPSFVNLYGSPREYSLLDD 135

                         170
                  ....*....|....*..
gi 528498301  525 PyEDLNYGKGEGVAYRG 541
Cdd:cd04018   136 H-QDLNEGLGEGVAYRG 151

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: 247.19 E-value: 1.24e-75

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1779 LRAVVWNTTEVILDETSITGENMSDIYVKGWMPGMEEDKQKTDVHYRSLDGDGNFNWRFVFGFDYLPAEQLCLVSRKEHF 1858
Cdd:cd08374     2 LRVIVWNTRDVLNDDTNITGEKMSDIYVKGWLDGLEEDKQKTDVHYRSLDGEGNFNWRFVFPFDYLPAEKKIVVIKKEHF 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 528498301 1859 WSLDKTEFRIPPKLTIQIWDNDKFSLDDYLGTVELDLLHLIPPAKTPEKCSL 1910
Cdd:cd08374    82 WSLDETEYKIPPKLTLQVWDNDKFSPDDFLGSLELDLSILPRPAKTSKKCGL 133

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: 223.19 E-value: 3.10e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1131 YHLRVYVYQARNLLPMDKDSFSDPYVHVSFLHASKTTEIIKSCLNPTWDQTLIFNDIEIYGDPQTIAYNPPNVVLEIYDS 1210
Cdd:cd04017     1 FQLRAYIYQARDLLAADKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTLIFDEVELYGSPEEIAQNPPLVVVELFDQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 528498301 1211 DQMGKDEAMGRCTCPPVVKLNPANPLIPKLFWFPISLKGRSAGEMLVAAELLLKE 1265
Cdd:cd04017    81 DSVGKDEFLGRSVAKPLVKLDLEEDFPPKLQWFPIYKGGQSAGELLAAFELIEVT 135

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: 213.57 E-value: 4.47e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1543 LVRIHIIRCLDLQPKDNNGMCDPYIKISLGRKTIDDRDHYKPNTLNPDFGRVFELNCYIPQDKDLKISVYDYDLLSSDEK 1622
Cdd:cd04037     1 LVRVYVVRARNLQPKDPNGKSDPYLKIKLGKKKINDRDNYIPNTLNPVFGKMFELEATLPGNSILKISVMDYDLLGSDDL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 528498301 1623 VGETVIDLENRLLSRFGSHCGIPKSYCVSGVNQWRDQLKPSQIL 1666
Cdd:cd04037    81 IGETVIDLEDRFFSKHRATCGLPPTYEESGPNQWRDSLKPSGIL 124

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: 188.94 E-value: 1.25e-55

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  202 PQDFQIRIRVIEGRQLPGNNIKPVAKVSVCGQTHRTRIRRGNN-PFFDEIFSYNVNMLPSELFDESIMIRVYNASSLRAD 280
Cdd:cd04011     1 PQDFQVRVRVIEARQLVGGNIDPVVKVEVGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELFDKIIKISVYDSRSLRSD 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 528498301  281 SLMGEFKLDVGYVYDETGHAIMRKWLLLGDP 311
Cdd:cd04011    81 TLIGSFKLDVGTVYDQPDHAFLRKWLLLTDP 111

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: 160.11 E-value: 2.59e-45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    5 VVESAKGIPKKTiGVPDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLKGSPlDSSSFIEVVVKDYETIGKDKFIGSV 84
Cdd:cd08373     1 LVVSLKNLPGLK-GKGDRIAKVTFRGVKKKTRVLENELNPVWNETFEWPLAGSP-DPDESLEIVVKDYEKVGRNRLIGSA 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 528498301   85 KISLKELAagqTRSLASKNTPLINEKKQEIGATINLTIAYEPPASTVPNLND 136
Cdd:cd08373    79 TVSLQDLV---SEGLLEVTEPLLDSNGRPTGATISLEVSYQPPDGAVGGWAD 127

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

Pssm-ID: 462376 Cd Length: 76 Bit Score: 135.03 E-value: 2.86e-37

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 528498301   774 PQNSMPDVIIWMLRGEKRVAYARIPANQVLYTThSEQAIGKYCGRTQTIFMQYPMDKNKG---LKIPVQLRVNMWLG 847
Cdd:pfam08150    1 PQNSLPDVFIWMLSGGKRVAYARIPAHDILFSP-VEEERGKFCGKVQTLFLKYPGKKAKGpagWEIPAKLRVYLWLG 76

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: 117.95 E-value: 2.75e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  1924 SLFSQKSVRGWWP---------------CAMEENGKK---------------------VLAGKVEMTLEVVEEKEADERP 1967
Cdd:pfam16165    4 SIFRAKRMKGWWPfiklksqedfereerEAKKKKKKKnkrsekkpedlefkdasgntfLLMGKVEAEFELLTVEEAEKSP 83

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528498301  1968 AGKGRDEPNmnpKLESPNRPDTSFLWFTNPCKTMKFIVWRKYKWLFIGLIILIPVILFIGILLYSFPNYLSMKL 2041
Cdd:pfam16165   84 VGKGRKEPE---PLEKPNRPKTSFSWFVNPMKTFIFFIWRRYKKYIIALLILAILALFLFLILYTLPGQISELI 154

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

Pssm-ID: 462389 Cd Length: 65 Bit Score: 98.42 E-value: 1.53e-24

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 528498301   682 AILAKVSDARLAEIWLKLVTQVIDDLSsYQLPDMEGKPNLTALDIQIKNLRDKTMTSVKEAAIRMR 747
Cdd:pfam08165    1 ALKAKVSEEELASLWLKLLDQLIEDCS-KPLPELEGKPNVTELDRQLRKLRKRALSQIKEAALKLR 65

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 90.46 E-value: 2.78e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  1542 CLVRIHIIRCLDLQPKDNNGMCDPYIKISLGRKTIDDRDHYKPNTLNPDFGRVFELNCYIPQDKDLKISVYDYDLLSSDE 1621
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDRFGRDD 80

                           90       100
                   ....*....|....*....|
gi 528498301  1622 KVGETVIDLENRLLSRFGSH 1641
Cdd:pfam00168   81 FIGEVRIPLSELDSGEGLDG 100

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 90.07 E-value: 3.41e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  1132 HLRVYVYQARNLLPMDKDSFSDPYVHVSFLHASKT--TEIIKSCLNPTWDQTLIFndiEIYGDPQTIaynppnVVLEIYD 1209
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKkkTKVVKNTLNPVWNETFTF---SVPDPENAV------LEIEVYD 72

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 528498301  1210 SDQMGKDEAMGRCTCPpvvkLNPANPLIPKLFWFPI 1245
Cdd:pfam00168   73 YDRFGRDDFIGEVRIP----LSELDSGEGLDGWYPL 104

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: 86.45 E-value: 1.58e-20

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 528498301   310 DPDDAVSGARGYLKVSMFIVGTGDEPPVEKREANEEQ-DDIESNLLLPAGV 359
Cdd:pfam08151    2 DPDDISAGVKGYLKVDISVLGKGDEPPVEPTDKTSDAeDDIEKNLLLPAGV 52

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 83.91 E-value: 5.84e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301     2 LRVVVESAKGIPKKTI-GVPDP--IAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLkgsPLDSSSFIEVVVKDYETIGKD 78
Cdd:pfam00168    3 LTVTVIEAKNLPPKDGnGTSDPyvKVYLLDGKQKKKTKVVKNTLNPVWNETFTFSV---PDPENAVLEIEVYDYDRFGRD 79

                           90
                   ....*....|....*..
gi 528498301    79 KFIGSVKISLKELAAGQ 95
Cdd:pfam00168   80 DFIGEVRIPLSELDSGE 96

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: 82.89 E-value: 1.38e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLHASK-TTEIIKSCLNPTWDQTLIFNDIEiygdpqtiaYNPPNVVLEIYDSD 1211
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQKfKTKVVKNTLNPVWNETFEFPVLD---------PESDTLTVEVWDKD 71

                          90       100       110
                  ....*....|....*....|....*....|....
gi 528498301 1212 QMGKDEAMGRCTCpPVVKLNPANPLIPKlfWFPI 1245
Cdd:cd00030    72 RFSKDDFLGEVEI-PLSELLDSGKEGEL--WLPL 102

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: 82.89 E-value: 1.42e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1544 VRIHIIRCLDLQPKDNNGMCDPYIKISLG----RKTiddrdHYKPNTLNPDFGRVFELNCYIPQDKDLKISVYDYDLLSS 1619
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGgkqkFKT-----KVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDRFSK 75

                          90
                  ....*....|...
gi 528498301 1620 DEKVGETVIDLEN 1632
Cdd:cd00030    76 DDFLGEVEIPLSE 88

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: 81.38 E-value: 4.55e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301   1543 LVRIHIIRCLDLQPKDNNGMCDPYIKISL-GRKTIDDRDHYKPNTLNPDFGRVFELNCYIPQDKDLKISVYDYDLLSSDE 1621
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLdGDPKEKKKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKDRFGRDD 80

                            90
                    ....*....|....*
gi 528498301   1622 KVGETVIDLENRLLS 1636
Cdd:smart00239   81 FIGQVTIPLSDLLLG 95

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: 79.42 E-value: 2.00e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKK-TIGVPDPIAGIIFRGEKK-KTKAIDKELNPVWNEIIEFDLkgsPLDSSSFIEVVVKDYETIGKDK 79
Cdd:cd00030     1 LRVTVIEARNLPAKdLNGKSDPYVKVSLGGKQKfKTKVVKNTLNPVWNETFEFPV---LDPESDTLTVEVWDKDRFSKDD 77

                          90
                  ....*....|..
gi 528498301   80 FIGSVKISLKEL 91
Cdd:cd00030    78 FLGEVEIPLSEL 89

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: 79.07 E-value: 2.67e-17

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301   1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLHASKT---TEIIKSCLNPTWDQTLIFNDIEIYGDPqtiaynppnVVLEIYD 1209
Cdd:smart00239    2 LTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKEkkkTKVVKNTLNPVWNETFEFEVPPPELAE---------LEIEVYD 72

                            90
                    ....*....|....*.
gi 528498301   1210 SDQMGKDEAMGRCTCP 1225
Cdd:smart00239   73 KDRFGRDDFIGQVTIP 88

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 77.74 E-value: 7.85e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301   365 TLSLKIYRAEDMPQMDdafaqtvkhifggtddKKNLVDPFVEVNF--AGKKVCTKIIEKNANPEWNQLIHLQVKFPsMCE 442
Cdd:pfam00168    2 RLTVTVIEAKNLPPKD----------------GNGTSDPYVKVYLldGKQKKKTKVVKNTLNPVWNETFTFSVPDP-ENA 64

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 528498301   443 RIKLTAFDWDRLSKNDVIGTTYLNLTKIASSGGEIEETP 481
Cdd:pfam00168   65 VLEIEVYDYDRFGRDDFIGEVRIPLSELDSGEGLDGWYP 103

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: 76.37 E-value: 2.63e-16

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301      2 LRVVVESAKGIPKKTI-GVPDPIAGIIFRG---EKKKTKAIDKELNPVWNEIIEFDLkgsPLDSSSFIEVVVKDYETIGK 77
Cdd:smart00239    2 LTVKIISARNLPPKDKgGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFEV---PPPELAELEIEVYDKDRFGR 78

                            90       100
                    ....*....|....*....|
gi 528498301     78 DKFIGSVKISLKELAAGQTR 97
Cdd:smart00239   79 DDFIGQVTIPLSDLLLGGRH 98

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: 74.03 E-value: 1.53e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  366 LSLKIYRAEDMPQMDDafaqtvkhifggtddkKNLVDPFVEVNFAGKKVC-TKIIEKNANPEWNQLIHLQVKFPsMCERI 444
Cdd:cd00030     1 LRVTVIEARNLPAKDL----------------NGKSDPYVKVSLGGKQKFkTKVVKNTLNPVWNETFEFPVLDP-ESDTL 63

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 528498301  445 KLTAFDWDRLSKNDVIGTTYLNLTKIASSGGEIEET 480
Cdd:cd00030    64 TVEVWDKDRFSKDDFLGEVEIPLSELLDSGKEGELW 99

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: 71.75 E-value: 9.06e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    365 TLSLKIYRAEDMPQMDdafaqtvkhifggtddKKNLVDPFVEVNFAG---KKVCTKIIEKNANPEWNQLIHLQVKFPSmC 441
Cdd:smart00239    1 TLTVKIISARNLPPKD----------------KGGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNETFEFEVPPPE-L 63

                            90       100       110
                    ....*....|....*....|....*....|....
gi 528498301    442 ERIKLTAFDWDRLSKNDVIGTTYLNLTKIASSGG 475
Cdd:smart00239   64 AELEIEVYDKDRFGRDDFIGQVTIPLSDLLLGGR 97

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: 66.50 E-value: 1.15e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1546 IHIIRCLDLQPKDNNGMCDPYIKISLGRKTIDD---RDHYKPNTLNPDFGRVFELNCYIPQD---KDLKISVYDYDLLSS 1619
Cdd:cd04031    20 VTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKskrRTKTVKKTLNPEWNQTFEYSNVRRETlkeRTLEVTVWDYDRDGE 99

                          90
                  ....*....|....*.
gi 528498301 1620 DEKVGETVIDLENRLL 1635
Cdd:cd04031   100 NDFLGEVVIDLADALL 115

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: 66.49 E-value: 1.81e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1545 RIHIIRCLDLQPKDNNGMCDPYIKISLG----------RKTiddRDHYKpnTLNPDFGRVFELNcyIPQDKDLK------ 1608
Cdd:cd04009    19 RVEILNARNLLPLDSNGSSDPFVKVELLprhlfpdvptPKT---QVKKK--TLFPLFDESFEFN--VPPEQCSVegalll 91

                          90       100
                  ....*....|....*....|....
gi 528498301 1609 ISVYDYDLLSSDEKVGETVIDLEN 1632
Cdd:cd04009    92 FTVKDYDLLGSNDFEGEAFLPLND 115

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: 63.70 E-value: 2.05e-12

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528498301    862 TFSVYAEMYENQAQ-VFGKWGSTGLVSRHKFSDV-TGKVKLKQERFMPPRSWDWEGD-WFID 920
Cdd:smart00693    1 PIRFTEEMYENQRRwLGGGWKTTLLPYRPKFSDAsGGKECLPKENLLPPPGWEWEDDnWSLD 62

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: 65.28 E-value: 2.42e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 528498301  396 DKKNLVDPFVEVNFAGKKVC-TKIIEKNANPEWNQliHLQVKFPSMCER-IKLTAFDWDRLSKNDVIGTTYLNLTKI 470
Cdd:cd04040    15 DRNGKSDPFVKFYLNGEKVFkTKTIKKTLNPVWNE--SFEVPVPSRVRAvLKVEVYDWDRGGKDDLLGSAYIDLSDL 89

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 63.88 E-value: 5.83e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301   206 QIRIRVIEGRQLPGNNIK----PVAKVSV--CGQTHRTRIRRGN-NPFFDEIFSYNVnmlpSELFDESIMIRVYNASSLR 278
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNgtsdPYVKVYLldGKQKKKTKVVKNTlNPVWNETFTFSV----PDPENAVLEIEVYDYDRFG 77

                           90       100       110
                   ....*....|....*....|....*....|
gi 528498301   279 ADSLMGEFKLDVGyvyDETGHAIMRKWLLL 308
Cdd:pfam00168   78 RDDFIGEVRIPLS---ELDSGEGLDGWYPL 104

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: 63.47 E-value: 1.55e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1542 CLVRIHIIRCLDLQPKDNN------GMCDPYIKISLGRKTIddRDHYKPNTLNPDFGRVFELNCYIPQDKDLKISVYDYD 1615
Cdd:cd08391     1 GVLRIHVIEAQDLVAKDKFvgglvkGKSDPYVIVRVGAQTF--KSKVIKENLNPKWNEVYEAVVDEVPGQELEIELFDED 78

                          90
                  ....*....|....*.
gi 528498301 1616 lLSSDEKVGETVIDLE 1631
Cdd:cd08391    79 -PDKDDFLGRLSIDLG 93

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: 63.37 E-value: 2.29e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1128 SFSYH-----LRVYVYQARNLLPMDKDSFSDPYVHVSFLHAS-----KTTEIIKSCLNPTWDQTLIFnDIEIYGDPQTia 1197
Cdd:cd00276     6 SLSYLptaerLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGkklkkKKTSVKKGTLNPVFNEAFSF-DVPAEQLEEV-- 82

                          90       100
                  ....*....|....*....|....*.
gi 528498301 1198 ynppNVVLEIYDSDQMGKDEAMGRCT 1223
Cdd:cd00276    83 ----SLVITVVDKDSVGRNEVIGQVV 104

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: 63.05 E-value: 2.74e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFL----HASK-TTEIIKSCLNPTWDQTLIFNdieiygdpQTIAYNPPNVVLEI 1207
Cdd:cd04026    15 LTVEVREAKNLIPMDPNGLSDPYVKLKLIpdpkNETKqKTKTIKKTLNPVWNETFTFD--------LKPADKDRRLSIEV 86

                          90
                  ....*....|...
gi 528498301 1208 YDSDQMGKDEAMG 1220
Cdd:cd04026    87 WDWDRTTRNDFMG 99

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: 62.27 E-value: 2.98e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1543 LVRIHIIRCLDLQPKDNNGMCDPYIKISLGRKTiddrdhYK----PNTLNPDFGRVFELNCYIPQDKDLKISVYDYDLLS 1618
Cdd:cd08376     1 VVTIVLVEGKNLPPMDDNGLSDPYVKFRLGNEK------YKskvcSKTLNPQWLEQFDLHLFDDQSQILEIEVWDKDTGK 74

                          90       100
                  ....*....|....*....|....
gi 528498301 1619 SDEKVGETVIDLENrlLSRFGSHC 1642
Cdd:cd08376    75 KDEFIGRCEIDLSA--LPREQTHS 96

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: 63.11 E-value: 3.21e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528498301  402 DPFVEVNFAGKKVCTKIIEKNANPEWNQliHLQVKFPSMCERIKLTAFDWDRLSKNDVIGTTYLNLTKIAS 472
Cdd:cd04038    23 DPYVVLTLGNQKVKTRVIKKNLNPVWNE--ELTLSVPNPMAPLKLEVFDKDTFSKDDSMGEAEIDLEPLVE 91

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: 62.42 E-value: 3.58e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1543 LVRIHIIRCLDLQPKDNNGMCDPYIKISL--GRKTI-DDRDHYKpnTLNPDFGR--VFELNCYIPQDKDLKISVYDYDLL 1617
Cdd:cd08387    17 ILNVKLIQARNLQPRDFSGTADPYCKVRLlpDRSNTkQSKIHKK--TLNPEFDEsfVFEVPPQELPKRTLEVLLYDFDQF 94

                          90
                  ....*....|....*
gi 528498301 1618 SSDEKVGETVIDLEN 1632
Cdd:cd08387    95 SRDECIGVVELPLAE 109

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: 61.84 E-value: 5.15e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    1 MLRVVVESAKG-IPKKTIGVPDPIAGIIFRGEKK-KTKAIDKELNPVWNEIIEFdlkgsPLDSSS---FIEVVvkDYETI 75
Cdd:cd04045     2 VLRLHIRKANDlKNLEGVGKIDPYVRVLVNGIVKgRTVTISNTLNPVWDEVLYV-----PVTSPNqkiTLEVM--DYEKV 74

                          90
                  ....*....|....*..
gi 528498301   76 GKDKFIGSVKISLKELA 92
Cdd:cd04045    75 GKDRSLGSVEINVSDLI 91

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 67.86 E-value: 7.46e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  348 DIESNLLLPAGVALrwATLSLKIYRAEDMPQMDDAFaqtvkhifggtddkKNLVDPFVEVNFAGKKV-CTKIIEKNANPE 426
Cdd:COG5038   422 DISQIMAGDSGTAI--GVVEVKIKSAEGLKKSDSTI--------------NGTVDPYITVTFSDRVIgKTRVKKNTLNPV 485

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  427 WNQLIHLQVKfpSMCERIKLTAFDWDRLSKNDVIGTTYLNLTKIASSGGEIEET--PSENglpsSFNVDTTEAEVGFLPA 504
Cdd:COG5038   486 WNETFYILLN--SFTDPLNLSLYDFNSFKSDKVVGSTQLDLALLHQNPVKKNELyeFLRN----TKNVGRLTYDLRFFPV 559

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  505 FGPcyinlygsPREFTGLPDPYEDLNYGKGEgvayrgRVLIELS--TQLNDKTDKKVEDLSNDNILVAQKYQRRRkyslc 582
Cdd:COG5038   560 IED--------KKELKGSVEPLEDSNTGILK------VTLREVKalDELSSKKDNKSAELYTNAKEVYSTGKLKF----- 620

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  583 avfhsacmLQEPGEPIQFEVSIGNYGN-------KLDSTCKPLA----STTQYSCAVFDGNHYYYLPWADSKpvVILTSF 651
Cdd:COG5038   621 --------TNHPSWNLQYNVLVTDRKNssikvvtFDVQSGKVIAtegsTLPDLIDRTLDTFLVFPLRNPKGR--IFITNY 690

                         330       340       350
                  ....*....|....*....|....*....|....*...
gi 528498301  652 WEDISHRLDSvNIILYISDRLQSNIISLKTAILAKVSD 689
Cdd:COG5038   691 WKPIYNAGGS-SSKTVYDTPIGAIRVSVRKANDLRNEI 727

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: 60.74 E-value: 1.40e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1546 IHIIRCLDLQPKDNNGMCDPYIKISL---GRKTIDDRDHYKpnTLNPDFGRVFELNcyIPQD----KDLKISVYDYDLLS 1618
Cdd:cd08385    20 VGIIQAADLPAMDMGGTSDPYVKVYLlpdKKKKFETKVHRK--TLNPVFNETFTFK--VPYSelgnKTLVFSVYDFDRFS 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 528498301 1619 SDEKVGETVIDLENRLLSRFgshcgipksycvsgVNQWRD 1658
Cdd:cd08385    96 KHDLIGEVRVPLLTVDLGHV--------------TEEWRD 121

C2A domain first 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 60.42 E-value: 1.73e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  365 TLSLKIYRAEDMPQMDdafaqtvkhiFGGTDDkknlvdPFVEVNF---AGKKVCTKIIEKNANPEWNQLIHLQvKFP--S 439
Cdd:cd08386    17 TLTLKILKAVELPAKD----------FSGTSD------PFVKIYLlpdKKHKLETKVKRKNLNPHWNETFLFE-GFPyeK 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 528498301  440 MCERI-KLTAFDWDRLSKNDVIGTTYLNLTKI 470
Cdd:cd08386    80 LQQRVlYLQVLDYDRFSRNDPIGEVSLPLNKV 111

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: 60.52 E-value: 1.97e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1545 RIHIIRCLDLQPKD--NNGMCDPYIKISLGRKTIddRDHYKPNTLNPDFGRVFELNCYIPQDKDLKISVYDYDLLSSDEK 1622
Cdd:cd04024     4 RVHVVEAKDLAAKDrsGKGKSDPYAILSVGAQRF--KTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRFAGKDY 81

                          90
                  ....*....|
gi 528498301 1623 VGETVIDLEN 1632
Cdd:cd04024    82 LGEFDIALEE 91

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: 60.42 E-value: 2.45e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSfSDPYVHVSFLHASKTTEIIKSCLNPTWDQTLIFndieiygdpqtIAYNPPNVV-LEIYDSD 1211
Cdd:cd04038     4 LKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTL-----------SVPNPMAPLkLEVFDKD 71


                  ....*....
gi 528498301 1212 QMGKDEAMG 1220
Cdd:cd04038    72 TFSKDDSMG 80

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: 60.05 E-value: 3.20e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1540 QECLVrIHIIRCLDLQPKDNNGMCDPYIKISL----GRKTiDDRDHYKPNTLNPDFGRVF--ELNCYIPQDKDLKISVYD 1613
Cdd:cd08384    12 RRGLI-VGIIRCVNLAAMDANGYSDPFVKLYLkpdaGKKS-KHKTQVKKKTLNPEFNEEFfyDIKHSDLAKKTLEITVWD 89

                          90
                  ....*....|.
gi 528498301 1614 YDLLSSDEKVG 1624
Cdd:cd08384    90 KDIGKSNDYIG 100

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: 59.17 E-value: 6.06e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1120 TVFCRFDKSfSYHLRVYVYQARNLLPMDKDSFSDPYVHVSFL--H-----ASKTTEIIKSCLNPTWDQTLIFNdIEiygD 1192
Cdd:cd04009     6 TVKAYYRAS-EQSLRVEILNARNLLPLDSNGSSDPFVKVELLprHlfpdvPTPKTQVKKKTLFPLFDESFEFN-VP---P 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 528498301 1193 PQtiaYNPPN--VVLEIYDSDQMGKDEAMGRCTCPP 1226
Cdd:cd04009    81 EQ---CSVEGalLLFTVKDYDLLGSNDFEGEAFLPL 113

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 64.40 E-value: 7.10e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    1 MLRVVVESAKGIPKKTIG-VPDPIAGIIFRGEKK-KTKAIDKELNPVWNEIIEFDLKgSPLDSssfIEVVVKDYETIGKD 78
Cdd:COG5038   712 AIRVSVRKANDLRNEIPGgKSDPYATVLVNNLVKyRTIYGSSTLNPIWNEILYVPVT-SKNQR---LTLECMDYEESGDD 787

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301   79 KFIGSVKISLKELAAGQTRS-LASKNTP--LINE---KKQEIGATINLTIAYEPPASTVPNLNDQNTGEANTKDtgAAEE 152
Cdd:COG5038   788 RNLGEVNINVSNVSKKDEDSaLMETIDGaeETGKlslTGKKVKGTITYKCRFYPAVIVLSLEEVRYVDKVSSEK--RKSE 865

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  153 EKAADSDED---AGDVADSGAPGVSptgQPGKKDSkkvvrTTRKRQKALANKPQDFQ--IRIRVIEGRqlpgnnikpVAK 227
Cdd:COG5038   866 KRKSALDEKtisLVDKEDSVEESIE---VEELTDM-----YSLKPKLDLNEALQYKSgvLGIQILSGE---------LPD 928

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  228 VSVCGQThrtrirrgnnpFFDEIfsynvnmlPSELFDESIMIRVYNASSLRADSLMGEFKLDVGYVydetghAIMRKWLL 307
Cdd:COG5038   929 PGQYLQI-----------FFDDA--------SHPQIVSSKAPTRGERNGESGDTFIRELEYSETTF------RVTKNAKK 983

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  308 LGDpddavsgargylKVSMFIVGTGDEPpvekREANEEQDDIESNLLLPAGVALRWATLSLKiYRAEDMpqMDDAFAQTV 387
Cdd:COG5038   984 SDK------------VVCEVTLPTLDLV----SNAYEKPSSLNFPGSAKVLVQVSYTPVPVK-LPPVEM--VENSGYLTI 1044

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  388 KHIfGGTD----DKKNLVDPFVEVNFAGKKVC-TKIIEKNANPEWNQLIHLQVKFPSMCErIKLTAFDWDRLSKNDVIGT 462
Cdd:COG5038  1045 MLR-SGENlpssDENGYSDPFVKLFLNEKSVYkTKVVKKTLNPVWNEEFTIEVLNRVKDV-LTINVNDWDSGEKNDLLGT 1122

                         490
                  ....*....|....*....
gi 528498301  463 TYLNLTKIASSGGEIEETP 481
Cdd:COG5038  1123 AEIDLSKLEPGGTTNSNIP 1141

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: 55.61 E-value: 1.66e-09

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528498301    933 HSEFTDEVYQNETRFPGGEWKSAAEP----YTDVNGEKAQSPEE-IECPTGWIWEDG-WNFD 988
Cdd:smart00693    1 PIRFTEEMYENQRRWLGGGWKTTLLPyrpkFSDASGGKECLPKEnLLPPPGWEWEDDnWSLD 62

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: 56.73 E-value: 1.71e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    206 QIRIRVIEGRQLPGNNIK----PVAKVSVCGQ---THRTRIRRGN-NPFFDEIFSYNVNmlpsELFDESIMIRVYNASSL 277
Cdd:smart00239    1 TLTVKIISARNLPPKDKGgksdPYVKVSLDGDpkeKKKTKVVKNTlNPVWNETFEFEVP----PPELAELEIEVYDKDRF 76

                            90       100
                    ....*....|....*....|..
gi 528498301    278 RADSLMGEFKLDVGYVYDETGH 299
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRH 98

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: 57.59 E-value: 2.11e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTI-GVPDPIAGI-IFRGE----KKKTKAIDKELNPVWNEIIEFDLKGSPLDSSSfIEVVVKDYETI 75
Cdd:cd00276    16 LTVVVLKARNLPPSDGkGLSDPYVKVsLLQGGkklkKKKTSVKKGTLNPVFNEAFSFDVPAEQLEEVS-LVITVVDKDSV 94

                          90
                  ....*....|...
gi 528498301   76 GKDKFIGSVKISL 88
Cdd:cd00276    95 GRNEVIGQVVLGP 107

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: 56.89 E-value: 3.18e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  365 TLSLKIYRAEDMPQMDdafaqtvkhiFGGTDDkknlvdPFVEV---NFAGKKVCTKIIEKNANPEWNQLIHLQVKFPSMC 441
Cdd:cd08385    17 QLTVGIIQAADLPAMD----------MGGTSD------PYVKVyllPDKKKKFETKVHRKTLNPVFNETFTFKVPYSELG 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 528498301  442 ER-IKLTAFDWDRLSKNDVIGTTYLNLTKIaSSGGEIEE 479
Cdd:cd08385    81 NKtLVFSVYDFDRFSKHDLIGEVRVPLLTV-DLGHVTEE 118

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: 56.89 E-value: 3.49e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    1 MLRVVVESAKG-IPKKTIGVPDPIAGIIF-----RGEKKKTKAIDKELNPVWNEIIEFDLKgsPLDSSSFIEVVVKDYET 74
Cdd:cd04026    14 KLTVEVREAKNlIPMDPNGLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETFTFDLK--PADKDRRLSIEVWDWDR 91

                          90
                  ....*....|....*..
gi 528498301   75 IGKDKFIGSVKISLKEL 91
Cdd:cd04026    92 TTRNDFMGSLSFGVSEL 108

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: 55.92 E-value: 3.85e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  207 IRIRVIEGRQLPGNNIK----PVAKVSVCG-QTHRTRIRRGN-NPFFDEIFSYNVNMLPSelfdESIMIRVYNASSLRAD 280
Cdd:cd00030     1 LRVTVIEARNLPAKDLNgksdPYVKVSLGGkQKFKTKVVKNTlNPVWNETFEFPVLDPES----DTLTVEVWDKDRFSKD 76

                          90       100
                  ....*....|....*....|....*...
gi 528498301  281 SLMGEFKLDVGYVYDETGHaiMRKWLLL 308
Cdd:cd00030    77 DFLGEVEIPLSELLDSGKE--GELWLPL 102

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: 56.66 E-value: 4.08e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1539 PQECLVRIHIIRCLDLQPKDNNGMCDPYIKISL--GRKTIDDRDH-YKPNTLNPDFGRVFELNcyIPQDK----DLKISV 1611
Cdd:cd08405    12 PTANRITVNIIKARNLKAMDINGTSDPYVKVWLmyKDKRVEKKKTvIKKRTLNPVFNESFIFN--IPLERlretTLIITV 89

                          90
                  ....*....|...
gi 528498301 1612 YDYDLLSSDEKVG 1624
Cdd:cd08405    90 MDKDRLSRNDLIG 102

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: 55.73 E-value: 6.77e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    4 VVVEsAKGIPK-KTIGVPDPIAGIIFRGEKKKTKAIDKELNPVWNEiiEFDLKGSPlDSSSFIEVVVKDYETIGKDKFIG 82
Cdd:cd08376     5 VLVE-GKNLPPmDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLE--QFDLHLFD-DQSQILEIEVWDKDTGKKDEFIG 80

                          90
                  ....*....|....*..
gi 528498301   83 SVKISLKELAAGQTRSL 99
Cdd:cd08376    81 RCEIDLSALPREQTHSL 97

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

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 55.76 E-value: 6.85e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLlpMDKDSF--------SDPYVHVSFLHASKTTEIIKSCLNPTWDQTLifnDIEIYGDPQTiaynppNVV 1204
Cdd:cd08391     3 LRIHVIEAQDL--VAKDKFvgglvkgkSDPYVIVRVGAQTFKSKVIKENLNPKWNEVY---EAVVDEVPGQ------ELE 71

                          90       100
                  ....*....|....*....|.
gi 528498301 1205 LEIYDSDQmGKDEAMGRCTCP 1225
Cdd:cd08391    72 IELFDEDP-DKDDFLGRLSID 91

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

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 55.81 E-value: 7.40e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    3 RVVVE--SAKGI-PKKTIGVPDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLKGSPLDSSSFIEV-VVKDYETIGKD 78
Cdd:cd04022     1 KLVVEvvDAQDLmPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPSRLSNLVLEVyVYNDRRSGRRR 80


                  ....*....
gi 528498301   79 KFIGSVKIS 87
Cdd:cd04022    81 SFLGRVRIS 89

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: 55.27 E-value: 7.43e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1544 VRIHIIRCLDLQPKDNNGMCDPYIKISLgrktiDDRDHYKPN----TLNPDFGRVFELNcyIP--QDKDLKISVYDYDLL 1617
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKFYL-----NGEKVFKTKtikkTLNPVWNESFEVP--VPsrVRAVLKVEVYDWDRG 73

                          90
                  ....*....|...
gi 528498301 1618 SSDEKVGETVIDL 1630
Cdd:cd04040    74 GKDDLLGSAYIDL 86

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: 55.37 E-value: 9.15e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1124 RFDKSFSyHLRVYVYQARNLLPMDKDSFSDPYVHVSFL-HASKT----TEIIKSCLNPTWDQTLIFNDIE 1188
Cdd:cd04035     9 LYDPANS-ALHCTIIRAKGLKAMDANGLSDPYVKLNLLpGASKAtklrTKTVHKTRNPEFNETLTYYGIT 77

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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: 175987 [Multi-domain] Cd Length: 162 Bit Score: 56.56 E-value: 9.59e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIP-KKTIGVPDPIAGIIF-----RGEKKKTKAIDKELNPVWNEIIEFDlKGSPLD-SSSFIEVVVKDYET 74
Cdd:cd04020    29 LHVWVKEAKNLPaLKSGGTSDSFVKCYLlpdksKKSKQKTPVVKKSVNPVWNHTFVYD-GVSPEDlSQACLELTVWDHDK 107

                          90
                  ....*....|....*.
gi 528498301   75 IGKDKFIGSVKISLKE 90
Cdd:cd04020   108 LSSNDFLGGVRLGLGT 123

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

Pssm-ID: 176016 [Multi-domain] Cd Length: 125 Bit Score: 55.31 E-value: 9.86e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPK-KTIGVPDPIAGIIFRGEKKKTKAIDKE--LNPVWNEIIEFDLKGSPLDSS-SFIEVVVKDYETIGK 77
Cdd:cd04051     2 LEITIISAEDLKNvNLFGKMKVYAVVWIDPSHKQSTPVDRDggTNPTWNETLRFPLDERLLQQGrLALTIEVYCERPSLG 81

                          90
                  ....*....|....*..
gi 528498301   78 DKFIGSVKISLKELAAG 94
Cdd:cd04051    82 DKLIGEVRVPLKDLLDG 98

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: 55.87 E-value: 1.02e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLH-----ASKTTEIIKSCLNPTWDQTLIFnDIEIYGDPQTiaynppNVVLEI 1207
Cdd:cd08402    17 LTVVILEAKNLKKMDVGGLSDPYVKIHLMQngkrlKKKKTTIKKRTLNPYYNESFSF-EVPFEQIQKV------HLIVTV 89

                          90
                  ....*....|....*.
gi 528498301 1208 YDSDQMGKDEAMGRCT 1223
Cdd:cd08402    90 LDYDRIGKNDPIGKVV 105

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: 55.12 E-value: 1.16e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKK---TIGVPDPIAgIIFRGEKK-KTKAIDKELNPVWNEIIEFDLKGSPldsSSFIEVVVKDYETIGK 77
Cdd:cd04024     3 LRVHVVEAKDLAAKdrsGKGKSDPYA-ILSVGAQRfKTQTIPNTLNPKWNYWCEFPIFSAQ---NQLLKLILWDKDRFAG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 528498301   78 DKFIGSVKISLKELAA----GQTRS---LASKNTPLINEKKQEI 114
Cdd:cd04024    79 KDYLGEFDIALEEVFAdgktGQSDKwitLKSTRPGKTSVVSGEI 122

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: 1.24e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPK-KTIGVPDPIAGIIFRGEK-KKTKAIDKELNPVWNEIIEFDLkgsPLDSSSFIEVVVKDYETIGKDK 79
Cdd:cd04040     1 LTVDVISAENLPSaDRNGKSDPFVKFYLNGEKvFKTKTIKKTLNPVWNESFEVPV---PSRVRAVLKVEVYDWDRGGKDD 77

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 528498301   80 FIGSVKISLKELAAGQTrslASKNTPLINEKKQEIGAT 117
Cdd:cd04040    78 LLGSAYIDLSDLEPEET---TELTLPLDGQGGGKLGAV 112

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: 55.50 E-value: 1.26e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528498301 1128 SFSYH-----LRVYVYQARNLLPMDKDSFSDPYVHVSFLHASK-----TTEIIKSCLNPTWDQTLIFN 1185
Cdd:cd08405     7 SLCYNptanrITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKrvekkKTVIKKRTLNPVFNESFIFN 74

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: 54.95 E-value: 1.48e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFL----HASKT-TEIIKSCLNPTWDQTLIFNDIEiygDPQTIaynppNVVLEI 1207
Cdd:cd04031    18 LIVTVLQARDLPPRDDGSLRNPYVKVYLLpdrsEKSKRrTKTVKKTLNPEWNQTFEYSNVR---RETLK-----ERTLEV 89

                          90
                  ....*....|....*...
gi 528498301 1208 --YDSDQMGKDEAMGRCT 1223
Cdd:cd04031    90 tvWDYDRDGENDFLGEVV 107

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: 54.41 E-value: 1.99e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTI-GVPDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLKGSPldsSSFIEVVVKDYETIGKDKF 80
Cdd:cd04025     2 LRCHVLEARDLAPKDRnGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGA---DSPLSVEVWDWDLVSKNDF 78

                          90
                  ....*....|....*
gi 528498301   81 IGSVKISLKELAAGQ 95
Cdd:cd04025    79 LGKVVFSIQTLQQAK 93

C2 domain first 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 second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 55.46 E-value: 2.04e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1124 RFDKSFSYHLRVYVYQARNLLPMDKDSFSDPYVHVSFLHAS-----------------------------KTTEIIKSCL 1174
Cdd:cd08676    21 REAEPPIFVLKVTVIEAKGLLAKDVNGFSDPYCMLGIVPASrernsekskkrkshrkkavlkdtvpaksiKVTEVKPQTL 100

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 528498301 1175 NPTWDQTLIFnDIEiygDPQTIAYNppnvvLEIYDSDqmgkDEAMG 1220
Cdd:cd08676   101 NPVWNETFRF-EVE---DVSNDQLH-----LDIWDHD----DDFLG 133

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: 54.95 E-value: 2.41e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1130 SYHLRVYvyQARNLLPMD--------------KDSFSDPYVHVSFLHASKTTEIIKSCLNPTWDQTLIFNDieiygdpqt 1195
Cdd:cd04018     1 RFIFKIY--RAEDLPQMDsgimanvkkaflgeKKELVDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPE--------- 69

                          90       100
                  ....*....|....*....|....*...
gi 528498301 1196 iaYNPP---NVVLEIYDSDQMGKDEAMG 1220
Cdd:cd04018    70 --MFPPlceRIKIQIRDWDRVGNDDVIG 95

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: 54.33 E-value: 2.43e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1125 FDKSFSYhLRVYVYQARNLLPMDKDSFSDPYVHVSFL---HASKTTEIIKSCLNPTWDQTLIFndiEIygDPQTIaynpP 1201
Cdd:cd08387    11 YDKDMGI-LNVKLIQARNLQPRDFSGTADPYCKVRLLpdrSNTKQSKIHKKTLNPEFDESFVF---EV--PPQEL----P 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 528498301 1202 NVVLEI--YDSDQMGKDEAMGrctcppVVKLNPAN 1234
Cdd:cd08387    81 KRTLEVllYDFDQFSRDECIG------VVELPLAE 109

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: 54.19 E-value: 2.76e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1137 VYQARNLLPMDKDSFSDPYVHVSFLHASK---TTEIIKSCLNPTWDQTLifnDIEI-YGDPQTIAYNppnvvleIYDSDQ 1212
Cdd:cd04043     7 IVRAENLKADSSNGLSDPYVTLVDTNGKRriaKTRTIYDTLNPRWDEEF---ELEVpAGEPLWISAT-------VWDRSF 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 528498301 1213 MGKDEAMGRCTcppvVKLNP---ANPLIPKLFWFPISLKGR 1250
Cdd:cd04043    77 VGKHDLCGRAS----LKLDPkrfGDDGLPREIWLDLDTQGR 113

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: 53.75 E-value: 3.16e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1544 VRIHIIRCLDLQPKDNNGMCDPYIKISLGRKtIDDRDHYKPNTLNPDFGRVFelncYIP---QDKDLKISVYDYDLLSSD 1620
Cdd:cd04045     3 LRLHIRKANDLKNLEGVGKIDPYVRVLVNGI-VKGRTVTISNTLNPVWDEVL----YVPvtsPNQKITLEVMDYEKVGKD 77

                          90
                  ....*....|..
gi 528498301 1621 EKVGETVIDLEN 1632
Cdd:cd04045    78 RSLGSVEINVSD 89

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: 52.96 E-value: 4.93e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVsFLHASK--TTEIIKSCLNPTWDQTLifnDIEIygdpqtiaynpPN-----VVL 1205
Cdd:cd04040     1 LTVDVISAENLPSADRNGKSDPFVKF-YLNGEKvfKTKTIKKTLNPVWNESF---EVPV-----------PSrvravLKV 65

                          90
                  ....*....|....*...
gi 528498301 1206 EIYDSDQMGKDEAMGRCT 1223
Cdd:cd04040    66 EVYDWDRGGKDDLLGSAY 83

C2 domain second repeat present in Synaptotagmins 3, 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 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 53.28 E-value: 6.02e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLH-----ASKTTEIIKSCLNPTWDQTLIFnDIEiygdPQTIayNPPNVVLEI 1207
Cdd:cd08403    16 LTLTIIKARNLKAMDITGFSDPYVKVSLMCegrrlKKKKTSVKKNTLNPTYNEALVF-DVP----PENV--DNVSLIIAV 88

                          90
                  ....*....|....*
gi 528498301 1208 YDSDQMGKDEAMGRC 1222
Cdd:cd08403    89 VDYDRVGHNELIGVC 103

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: 53.03 E-value: 6.21e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1546 IHIIRCLDLQPKDNNGM-CDPYIKISLgrkTIDDRDH----YKPNTLNPDFGRVFELNcyIP----QDKDLKISVYDYDL 1616
Cdd:cd08390    18 VSLIKARNLPPRTKDVAhCDPFVKVCL---LPDERRSlqskVKRKTQNPNFDETFVFQ--VSfkelQRRTLRLSVYDVDR 92

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 528498301 1617 LSSDEKVGETVIDLENRLLsrfgshcgipksycVSGVNQWRD 1658
Cdd:cd08390    93 FSRHCIIGHVLFPLKDLDL--------------VKGGVVWRD 120

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: 53.17 E-value: 6.91e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1546 IHIIRCLDLQPKDNNGMCDPYIKISL---GRKTIDDRDHYKPNTLNPDFGRVFELNcyIP----QDKDLKISVYDYDLLS 1618
Cdd:cd08402    19 VVILEAKNLKKMDVGGLSDPYVKIHLmqnGKRLKKKKTTIKKRTLNPYYNESFSFE--VPfeqiQKVHLIVTVLDYDRIG 96

                          90
                  ....*....|
gi 528498301 1619 SDEKVGETVI 1628
Cdd:cd08402    97 KNDPIGKVVL 106

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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: 175996 [Multi-domain] Cd Length: 127 Bit Score: 53.05 E-value: 7.81e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 528498301 1132 HLRVYVYQARNLLPMDKDSFSDPYVHVSFL-----HASKTTEIIKSCLNPTWDQTLIF 1184
Cdd:cd04030    17 KLIVTVHKCRNLPPCDSSDIPDPYVRLYLLpdkskSTRRKTSVKKDNLNPVFDETFEF 74

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: 52.49 E-value: 8.78e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  396 DKKNLVDPFVEVNFAGKKVCTKIIEKNANPEWNQLIHLQVKFPSMcERIKLTAFDWDRLSKNDVIGTTYLNLTKIASSGG 475
Cdd:cd04025    16 DRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGAD-SPLSVEVWDWDLVSKNDFLGKVVFSIQTLQQAKQ 94


                  .
gi 528498301  476 E 476
Cdd:cd04025    95 E 95

C2 domain second repeat present in Synaptotagmins 3, 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 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 52.90 E-value: 9.47e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1539 PQECLVRIHIIRCLDLQPKDNNGMCDPYIKISL---GRKTIDDRDHYKPNTLNPDFGR--VFELNCYIPQDKDLKISVYD 1613
Cdd:cd08403    11 PTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLmceGRRLKKKKTSVKKNTLNPTYNEalVFDVPPENVDNVSLIIAVVD 90

                          90
                  ....*....|.
gi 528498301 1614 YDLLSSDEKVG 1624
Cdd:cd08403    91 YDRVGHNELIG 101

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 52.76 E-value: 1.04e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTIGVPDPIAGIIF----RGEKKKTKAIDKELNPVWNEIIEFDL-KGSPLDSSSFI---------EV 67
Cdd:cd08675     1 LSVRVLECRDLALKSNGTCDPFARVTLnyssKTDTKRTKVKKKTNNPRFDEAFYFELtIGFSYEKKSFKveeedleksEL 80

                          90       100
                  ....*....|....*....|....*.
gi 528498301   68 VV--KDYETIGKDKFIGSVKISLKEL 91
Cdd:cd08675    81 RVelWHASMVSGDDFLGEVRIPLQGL 106

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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: 175996 [Multi-domain] Cd Length: 127 Bit Score: 52.28 E-value: 1.10e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKT-IGVPDPIAGIIF-----RGEKKKTKAIDKELNPVWNEIIEFDLKGSPLdSSSFIEVVVKDYETI 75
Cdd:cd04030    18 LIVTVHKCRNLPPCDsSDIPDPYVRLYLlpdksKSTRRKTSVKKDNLNPVFDETFEFPVSLEEL-KRRTLDVAVKNSKSF 96

                          90       100
                  ....*....|....*....|....*
gi 528498301   76 --GKDKFIGSVKISLKE--LAAGQT 96
Cdd:cd04030    97 lsREKKLLGQVLIDLSDldLSKGFT 121

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: 52.10 E-value: 1.23e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLHASKTTEIIKSCLNPTWDQTLIFNDIEIYGDPQTIaynppnvvlEIYDSDQ 1212
Cdd:cd04025     2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKKSCYPRWNEVFEFELMEGADSPLSV---------EVWDWDL 72

                          90
                  ....*....|....
gi 528498301 1213 MGKDEAMGRCTCPP 1226
Cdd:cd04025    73 VSKNDFLGKVVFSI 86

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: 52.43 E-value: 1.29e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1128 SFSYH-----LRVYVYQARNLLPMDKDSFSDPYVHVSFLH-----ASKTTEIIKSCLNPtwdqtlIFNDIEIYGDPqtiA 1197
Cdd:cd08404     7 SLCYQpttnrLTVVVLKARHLPKMDVSGLADPYVKVNLYYgkkriSKKKTHVKKCTLNP------VFNESFVFDIP---S 77

                          90       100
                  ....*....|....*....|....*...
gi 528498301 1198 YNPPNVVLEI--YDSDQMGKDEAMGRCT 1223
Cdd:cd08404    78 EELEDISVEFlvLDSDRVTKNEVIGRLV 105

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: 52.36 E-value: 1.35e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1132 HLRVYVYQARNLlpMDKDSF--SDPYVHVSF-------LHASKTTEIIKSCLNPTWDQTLIFNdieiygdpqtiaYNPPN 1202
Cdd:cd04033     1 ILRVKVLAGIDL--AKKDIFgaSDPYVKISLydpdgngEIDSVQTKTIKKTLNPKWNEEFFFR------------VNPRE 66

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1203 --VVLEIYDSDQMGKDEAMGRCTCP----PVVKLNPANPLIPKLFWF-PISLKGRSAGEM 1255
Cdd:cd04033    67 hrLLFEVFDENRLTRDDFLGQVEVPlnnlPTETPGNERRYTFKDYLLrPRSSKSRVKGHL 126

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: 51.89 E-value: 1.40e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1543 LVRIHIIRCLDLQPKDNNGMCDPYIKISLGRKTIddrdhYKPNT----LNPDFGRVFELNCYIPqDKDLKISVYDYDLLS 1618
Cdd:cd04042     1 QLDIHLKEGRNLAARDRGGTSDPYVKFKYGGKTV-----YKSKTiyknLNPVWDEKFTLPIEDV-TQPLYIKVFDYDRGL 74

                          90
                  ....*....|....*....
gi 528498301 1619 SDEKVGETVIDLENRLLSR 1637
Cdd:cd04042    75 TDDFMGSAFVDLSTLELNK 93

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: 52.04 E-value: 1.49e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSF--SDPYVHVSFLHASKTTEIIKSCLNPTWDQTLifnDIEIYGdpqtiaynPPNVVLEI--Y 1208
Cdd:cd04024     3 LRVHVVEAKDLAAKDRSGKgkSDPYAILSVGAQRFKTQTIPNTLNPKWNYWC---EFPIFS--------AQNQLLKLilW 71

                          90
                  ....*....|...
gi 528498301 1209 DSDQMGKDEAMGR 1221
Cdd:cd04024    72 DKDRFAGKDYLGE 84

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

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 51.95 E-value: 1.65e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLHASKTTEIIKSCLNPTWDQTLIFNdieiYGDPQtiayNPPNVVLEIY 1208
Cdd:cd04022     2 LVVEVVDAQDLMPKDGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFN----VSDPS----RLSNLVLEVY 69

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: 51.90 E-value: 1.67e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1547 HIIRCLDLQPKDNNGMCDPYIKISL---GRKTIDDRDHYKPNTLNPDFGRvfELNCY-----IPQDKDLKISVYDYDLLS 1618
Cdd:cd04035    20 TIIRAKGLKAMDANGLSDPYVKLNLlpgASKATKLRTKTVHKTRNPEFNE--TLTYYgiteeDIQRKTLRLLVLDEDRFG 97

                          90
                  ....*....|....
gi 528498301 1619 SDeKVGETVIDLEN 1632
Cdd:cd04035    98 ND-FLGETRIPLKK 110

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: 51.52 E-value: 1.80e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTIGVP-------DPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLKGSPlDSSSFIEVVVKDyet 74
Cdd:cd08391     3 LRIHVIEAQDLVAKDKFVGglvkgksDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVDEVP-GQELEIELFDED--- 78

                          90
                  ....*....|....*.
gi 528498301   75 IGKDKFIGSVKISLKE 90
Cdd:cd08391    79 PDKDDFLGRLSIDLGS 94

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 51.99 E-value: 1.80e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1544 VRIHIIRCLDLQPKdNNGMCDPYIKISL--GRKTIDDRDHYKPNTLNPDFGRVFELNCYIPQDKD--------------- 1606
Cdd:cd08675     1 LSVRVLECRDLALK-SNGTCDPFARVTLnySSKTDTKRTKVKKKTNNPRFDEAFYFELTIGFSYEkksfkveeedlekse 79

                          90       100
                  ....*....|....*....|....*.
gi 528498301 1607 LKISVYDYDLLSSDEKVGETVIDLEN 1632
Cdd:cd08675    80 LRVELWHASMVSGDDFLGEVRIPLQG 105

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: 51.89 E-value: 1.90e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTIGVPDPIAGIIFRGEK-KKTKAIDKELNPVWNEIieFDLKGSPldsSSFIEVVVKDYETIGKDKF 80
Cdd:cd04021     4 LQITVESAKLKSNSKSFKPDPYVEVTVDGQPpKKTEVSKKTSNPKWNEH--FTVLVTP---QSTLEFKVWSHHTLKADVL 78

                          90
                  ....*....|.
gi 528498301   81 IGSVKISLKEL 91
Cdd:cd04021    79 LGEASLDLSDI 89

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: 51.56 E-value: 1.91e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    1 MLRVVVESAKGIPKKT-IGVPDPIAGIIFRGEKKKTK-AIDKELNPVWNEIIEFDLKGSPLDSSSFIEVVVKDYETIGKD 78
Cdd:cd04049     2 TLEVLLISAKGLQDTDfLGKIDPYVIIQCRTQERKSKvAKGDGRNPEWNEKFKFTVEYPGWGGDTKLILRIMDKDNFSDD 81

                          90
                  ....*....|...
gi 528498301   79 KFIGSVKISLKEL 91
Cdd:cd04049    82 DFIGEATIHLKGL 94

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: 51.66 E-value: 2.45e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTI-GVPDPIAGI-IFRGE----KKKTKAIDKELNPVWNEIIEFDLKGSPLDSSSfIEVVVKDYETI 75
Cdd:cd08404    17 LTVVVLKARHLPKMDVsGLADPYVKVnLYYGKkrisKKKTHVKKCTLNPVFNESFVFDIPSEELEDIS-VEFLVLDSDRV 95

                          90       100
                  ....*....|....*....|.
gi 528498301   76 GKDKFIGSVKISLKELAAGQT 96
Cdd:cd08404    96 TKNEVIGRLVLGPKASGSGGH 116

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: 50.53 E-value: 2.68e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1802 SDIYVKGWMPGmeEDKQKTDVHYRSLdgdgNFNWRFVFGFDYLPAEQlclvsrkehfwsldktefripPKLTIQIWDNDK 1881
Cdd:cd00030    20 SDPYVKVSLGG--KQKFKTKVVKNTL----NPVWNETFEFPVLDPES---------------------DTLTVEVWDKDR 72

                          90       100
                  ....*....|....*....|....*.
gi 528498301 1882 FSLDDYLGTVELDLLHLIPPAKTPEK 1907
Cdd:cd00030    73 FSKDDFLGEVEIPLSELLDSGKEGEL 98

C2A domain first 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 50.79 E-value: 3.71e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1546 IHIIRCLDLQPKDNNGMCDPYIKISLgrktIDDRDH-----YKPNTLNPDFGRVFELNCYiP----QDKDLKISVYDYDL 1616
Cdd:cd08386    20 LKILKAVELPAKDFSGTSDPFVKIYL----LPDKKHkletkVKRKNLNPHWNETFLFEGF-PyeklQQRVLYLQVLDYDR 94

                          90
                  ....*....|....*.
gi 528498301 1617 LSSDEKVGETVIDLEN 1632
Cdd:cd08386    95 FSRNDPIGEVSLPLNK 110

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: 50.63 E-value: 3.79e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  393 GTDDKKNLVDPFVEVNFAGKKVC--TKIIEKNANPEWNQLIHLQVKfpSMCERIKLTAFDWDRLSKNDVIGTTYLNLtki 470
Cdd:cd04044    16 GSDIIGGTVDPYVTFSISNRRELarTKVKKDTSNPVWNETKYILVN--SLTEPLNLTVYDFNDKRKDKLIGTAEFDL--- 90

                          90
                  ....*....|....*.
gi 528498301  471 assgGEIEETPSENGL 486
Cdd:cd04044    91 ----SSLLQNPEQENL 102

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: 51.20 E-value: 3.94e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    1 MLRVVVESAKGIPKKTI-GVPDPIAGI-IFRGEKKK------TKAIDKELNPVWNEiiEFDLKGSPLDSSSFIEVVvkDY 72
Cdd:cd04033     1 ILRVKVLAGIDLAKKDIfGASDPYVKIsLYDPDGNGeidsvqTKTIKKTLNPKWNE--EFFFRVNPREHRLLFEVF--DE 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 528498301   73 ETIGKDKFIGSVKISLKEL---AAGQTRSLASKNTPLIN-EKKQEIGATINLTIAY 124
Cdd:cd04033    77 NRLTRDDFLGQVEVPLNNLpteTPGNERRYTFKDYLLRPrSSKSRVKGHLRLYMAY 132

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: 50.38 E-value: 4.23e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    1 MLRVVVESAKGIPKKTI-GVPDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLKgsplDSSSFIEVVVKDYETIGKDK 79
Cdd:cd08377     2 FLQVKVIRASGLAAADIgGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIK----DIHDVLEVTVYDEDKDKKPE 77

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 528498301   80 FIGSVKISLKELAAGQTRSLASKNTPLINEKKQEI 114
Cdd:cd08377    78 FLGKVAIPLLSIKNGERKWYALKDKKLRTRAKGSI 112

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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-I topology.

Pssm-ID: 176029 [Multi-domain] Cd Length: 117 Bit Score: 50.34 E-value: 4.38e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKtiGVPDPIAGIIFRGEK-KKTKAIDKeLNPVWNEiiEFDLKGSPLDSSSF-IEVVVKDYETIGKDK 79
Cdd:cd08383     2 LRLRILEAKNLPSK--GTRDPYCTVSLDQVEvARTKTVEK-LNPFWGE--EFVFDDPPPDVTFFtLSFYNKDKRSKDRDI 76

                          90
                  ....*....|....*..
gi 528498301   80 FIGsvKISLKELAAGQT 96
Cdd:cd08383    77 VIG--KVALSKLDLGQG 91

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: 50.81 E-value: 4.69e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1543 LVRIHIIRCLDLQPKDNNGMCDPYIKISL----GRKTIDD-RDHYKPNTLNPDFGRVFELNCYiPQDKDLKISVYDYDLL 1617
Cdd:cd04033     1 ILRVKVLAGIDLAKKDIFGASDPYVKISLydpdGNGEIDSvQTKTIKKTLNPKWNEEFFFRVN-PREHRLLFEVFDENRL 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 528498301 1618 SSDEKVGETVIDLENRLLSRFGSHCGIP-KSY 1648
Cdd:cd04033    80 TRDDFLGQVEVPLNNLPTETPGNERRYTfKDY 111

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: 50.56 E-value: 5.47e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1544 VRIHIIRCLDLQPKDNNGMCDPYIKISLGRKTIDDRDHYKpnTLNPDFGRVFELNCYIPQDKDLKISVYDYDLLSSDEKV 1623
Cdd:cd04025     2 LRCHVLEARDLAPKDRNGTSDPFVRVFYNGQTLETSVVKK--SCYPRWNEVFEFELMEGADSPLSVEVWDWDLVSKNDFL 79


                  ....*...
gi 528498301 1624 GETVIDLE 1631
Cdd:cd04025    80 GKVVFSIQ 87

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: 5.55e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTI---GVPDP-----IAGI-IFRGEKKKTKAIDKE-LNPVWNEIIEFDLKgspLDSSSFIEVVVKD 71
Cdd:cd00275     4 LTIKIISGQQLPKPKGdkgSIVDPyveveIHGLpADDSAKFKTKVVKNNgFNPVWNETFEFDVT---VPELAFLRFVVYD 80

                          90       100
                  ....*....|....*....|...
gi 528498301   72 YETIGkDKFIGSVKISLKELAAG 94
Cdd:cd00275    81 EDSGD-DDFLGQACLPLDSLRQG 102

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176013 [Multi-domain] Cd Length: 120 Bit Score: 50.26 E-value: 5.87e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1140 ARNLLPMDKDSFSDPYVHVSFLHASKT-------TEIIKSCLNPTWDQTLIFND-IEIYgdpqtiaynpPNVVLEIYDSD 1211
Cdd:cd04048     9 CRNLLDKDVLSKSDPFVVVYVKTGGSGqwveigrTEVIKNNLNPDFVTTFTVDYyFEEV----------QKLRFEVYDVD 78

                          90
                  ....*....|....*..
gi 528498301 1212 ----QMGKDEAMGRCTC 1224
Cdd:cd04048    79 skskDLSDHDFLGEAEC 95

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: 50.46 E-value: 6.36e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1544 VRIHIIRCLDLQPKDNNGMCDPYIKISLGRKtiDDRDHYKPNTLNPDFGRVFELNCYIPQDKDLKISVYDYDLLSSDEKV 1623
Cdd:cd08375    17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQ--EHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCITVFDRDFFSPDDFL 94

                          90       100
                  ....*....|....*....|....
gi 528498301 1624 GETVIDLENRLLSRFGSHCGIPKS 1647
Cdd:cd08375    95 GRTEIRVADILKETKESKGPITKR 118

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. 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: 176004 [Multi-domain] Cd Length: 108 Bit Score: 49.56 E-value: 6.67e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1544 VRIHIIRCLDLQPKDN----NGMCDPYIKISLGRKTIddRDHYKPNTLNPDFGRVFELNCYiPQDK--DLKISVYDYDLL 1617
Cdd:cd04039     3 VFMEIKSITDLPPLKNmtrtGFDMDPFVIISFGRRVF--RTSWRRHTLNPVFNERLAFEVY-PHEKnfDIQFKVLDKDKF 79

                          90
                  ....*....|....*
gi 528498301 1618 SSDEKVGETVIDLEN 1632
Cdd:cd04039    80 SFNDYVATGSLSVQE 94

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: 49.61 E-value: 6.68e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFS-DPYVHVSFLHASKTTEIIKSCLNPTW-DQTLIF--NDIEIYGDPqtiaynppnVVLEIY 1208
Cdd:cd08688     1 LKVRVVAARDLPVMDRSSDLtDAFVEVKFGSTTYKTDVVKKSLNPVWnSEWFRFevDDEELQDEP---------LQIRVM 71

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 528498301 1209 DSDQMGKDEAMGRC--TCPPVVKLNPANPLIpklFWFPI 1245
Cdd:cd08688    72 DHDTYSANDAIGKVyiDLNPLLLKDSVSQIS---GWFPI 107

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176012 [Multi-domain] Cd Length: 110 Bit Score: 49.49 E-value: 7.89e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528498301   34 KTKAIDKELNPVWNEiieFDLKGSPL---DSSSFIEVVVKDYETIGKDKFIGSVKISLKELAAGQTRSLaskntPLIN 108
Cdd:cd04047    41 RTEVIKNTLNPVWKP---FTIPLQKLcngDYDRPIKIEVYDYDSSGKHDLIGEFETTLDELLKSSPLEF-----ELIN 110

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: 49.94 E-value: 8.35e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTIGV-PDPIAGIIF---RGEKKK--TKAIDKELNPVWNEIIEF------DLKgspldsSSFIEVVV 69
Cdd:cd04031    18 LIVTVLQARDLPPRDDGSlRNPYVKVYLlpdRSEKSKrrTKTVKKTLNPEWNQTFEYsnvrreTLK------ERTLEVTV 91

                          90
                  ....*....|....*....
gi 528498301   70 KDYETIGKDKFIGSVKISL 88
Cdd:cd04031    92 WDYDRDGENDFLGEVVIDL 110

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: 49.86 E-value: 9.25e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528498301  396 DKKNLVDPFVEVNFAGKKVCTK--IIEKNANPEWNQLIHLQVKFPsMCERIKLTAFDWDRLSKNDVIGTTYLNL 467
Cdd:cd04037    16 DPNGKSDPYLKIKLGKKKINDRdnYIPNTLNPVFGKMFELEATLP-GNSILKISVMDYDLLGSDDLIGETVIDL 88

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: 50.11 E-value: 1.04e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528498301   29 RGEKKKTKAIDKELNPVWNEIIEFDLKGSPLDSSSFIeVVVKDYETIGKDKFIGSVKISLKE 90
Cdd:cd08405    50 RVEKKKTVIKKRTLNPVFNESFIFNIPLERLRETTLI-ITVMDKDRLSRNDLIGKIYLGWKS 110

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

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 48.64 E-value: 1.25e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301   1801 MSDIYVKGWMPGMEEDKQKTDVHYRSLdgdgNFNWRFVFGFDYLPAEQLCLVsrkehfwsldktefrippkltIQIWDND 1880
Cdd:smart00239   20 KSDPYVKVSLDGDPKEKKKTKVVKNTL----NPVWNETFEFEVPPPELAELE---------------------IEVYDKD 74

                            90
                    ....*....|....*....
gi 528498301   1881 KFSLDDYLGTVELDLLHLI 1899
Cdd:smart00239   75 RFGRDDFIGQVTIPLSDLL 93

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: 49.50 E-value: 1.41e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1548 IIRCLDLQPKDNNGMCDPYIKISL---GRKTIDDRDHYKPNTLNPDFGR--VFELNCYIPQDKDLKISVYDYDLLSSDEK 1622
Cdd:cd00276    20 VLKARNLPPSDGKGLSDPYVKVSLlqgGKKLKKKKTSVKKGTLNPVFNEafSFDVPAEQLEEVSLVITVVDKDSVGRNEV 99

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 528498301 1623 VGETVIdlenrllsrfGSHCGIPksycvsGVNQWRD 1658
Cdd:cd00276   100 IGQVVL----------GPDSGGE------ELEHWNE 119

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: 49.69 E-value: 1.46e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLHASKTTEIIKSCLNPTWDQTLIFNDIEIYGDPQTIAynppnvvleIYDSDQ 1212
Cdd:cd08375    17 LMVVIVEGRDLKPCNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKDLEQDVLCIT---------VFDRDF 87


                  ....*....
gi 528498301 1213 MGKDEAMGR 1221
Cdd:cd08375    88 FSPDDFLGR 96

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 53.61 E-value: 1.65e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTI-GVPDPIAGIIFRGEK-KKTKAIDKELNPVWNE--IIEFDLKgspldSSSFIEVVVKDYETIGK 77
Cdd:COG5038  1042 LTIMLRSGENLPSSDEnGYSDPFVKLFLNEKSvYKTKVVKKTLNPVWNEefTIEVLNR-----VKDVLTINVNDWDSGEK 1116

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 528498301   78 DKFIGSVKISLKELAAGQTRSLaskNTPLINEKKQEIGATINL 120
Cdd:COG5038  1117 NDLLGTAEIDLSKLEPGGTTNS---NIPLDGKTFIVLDGTLHP 1156

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: 48.31 E-value: 2.92e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1134 RVYVYQARNLLPMDKDSFSDPYVHVSFLHasktTEI------IKSCLNPTWDQTLIFnDIEIYGDPQtiaynppnVVLEI 1207
Cdd:cd04037     3 RVYVVRARNLQPKDPNGKSDPYLKIKLGK----KKIndrdnyIPNTLNPVFGKMFEL-EATLPGNSI--------LKISV 69

                          90
                  ....*....|....
gi 528498301 1208 YDSDQMGKDEAMGR 1221
Cdd:cd04037    70 MDYDLLGSDDLIGE 83

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: 47.96 E-value: 2.98e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1539 PQECLVRIHIIRCLDLQpkdnNGMCDPYIKISLGRKTIDDRdhYKPNTLNPDFGRVFELNCYIP----QDKDLKISVYDY 1614
Cdd:cd04011     1 PQDFQVRVRVIEARQLV----GGNIDPVVKVEVGGQKKYTS--VKKGTNCPFYNEYFFFNFHESpdelFDKIIKISVYDS 74

                          90
                  ....*....|....*.
gi 528498301 1615 DLLSSDEKVGETVIDL 1630
Cdd:cd04011    75 RSLRSDTLIGSFKLDV 90

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: 48.86 E-value: 3.01e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1543 LVRIHIIRCLDLQPKDNNGmCDPYIKISLGRKTIDDRDHYkpNTLNPDFGRvfELNCYIPQDKD-LKISVYDYDLLSSDE 1621
Cdd:cd04038     3 LLKVRVVRGTNLAVRDFTS-SDPYVVLTLGNQKVKTRVIK--KNLNPVWNE--ELTLSVPNPMApLKLEVFDKDTFSKDD 77

                          90
                  ....*....|
gi 528498301 1622 KVGETVIDLE 1631
Cdd:cd04038    78 SMGEAEIDLE 87

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: 48.05 E-value: 3.02e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTI-GVPDPIAGI-IFRGE----KKKTKAIDKELNPVWNE------IIEFDLKGSPLdsssfiEVVV 69
Cdd:cd04035    17 LHCTIIRAKGLKAMDAnGLSDPYVKLnLLPGAskatKLRTKTVHKTRNPEFNEtltyygITEEDIQRKTL------RLLV 90

                          90       100
                  ....*....|....*....|....*....
gi 528498301   70 KDYETIGKDkFIGSVKISLKELAAGQTRS 98
Cdd:cd04035    91 LDEDRFGND-FLGETRIPLKKLKPNQTKQ 118

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. 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 synaptotagmin1. 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: 176063 [Multi-domain] Cd Length: 118 Bit Score: 48.01 E-value: 3.28e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLlP----MDKdsfSDPYVHVSFLHASKTTE-IIKSCLNPTWDQTLIFndiEIYGDPQTIAYnppnvvLEI 1207
Cdd:cd08681     3 LVVVVLKARNL-PnkrkLDK---QDPYCVLRIGGVTKKTKtDFRGGQHPEWDEELRF---EITEDKKPILK------VAV 69

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 528498301 1208 YDsDQMGKDEAMGRCTcppvVKLNPAnpLIPKLF--WFPISLKGRSAGEMLV 1257
Cdd:cd08681    70 FD-DDKRKPDLIGDTE----VDLSPA--LKEGEFddWYELTLKGRYAGEVYL 114

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: 48.31 E-value: 3.61e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 528498301  394 TDDKKNLVDPFVEVNFAG------KKVCTKIIEKNA-NPEWNQLIHLQVKFPSMCErIKLTAFDWDRlSKNDVIGTTYL 465
Cdd:cd00275    18 KGDKGSIVDPYVEVEIHGlpaddsAKFKTKVVKNNGfNPVWNETFEFDVTVPELAF-LRFVVYDEDS-GDDDFLGQACL 94

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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: 176056 [Multi-domain] Cd Length: 123 Bit Score: 48.02 E-value: 4.11e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1542 CLVRIHIIRCLDLQPKDN-NGMCDPYIKISL--------GRKTIddrdhYKPNTLNPDFGRVfeLNCYIPQD----KDLK 1608
Cdd:cd08521    14 GSLEVHIKECRNLAYADEkKKRSNPYVKVYLlpdkskqsKRKTS-----VKKNTTNPVFNET--LKYHISKSqletRTLQ 86

                          90       100       110
                  ....*....|....*....|....*....|....
gi 528498301 1609 ISVYDYDLLSSDEKVGETVIDLENRLLSRFGSHC 1642
Cdd:cd08521    87 LSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSEW 120

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: 48.02 E-value: 4.20e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528498301 1152 SDPYVHVSFLHASKTTEIIKSCLNPTWDQTLIFNdieIYGDPQtiaynpPNVVLEI--YDSDQMGKDEAMGRCT 1223
Cdd:cd08373    15 GDRIAKVTFRGVKKKTRVLENELNPVWNETFEWP---LAGSPD------PDESLEIvvKDYEKVGRNRLIGSAT 79

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). 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 type-II topology.

Pssm-ID: 176028 [Multi-domain] Cd Length: 123 Bit Score: 47.69 E-value: 4.24e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    1 MLRVVVESAKGIPKKTI-GVPDPIAGIIFRGEK-KKTKAIDKELNPVWNEiiEFDLKGSPldsSSFIEVVVKDYETIGK- 77
Cdd:cd08382     1 KVRLTVLCADGLAKRDLfRLPDPFAVITVDGGQtHSTDVAKKTLDPKWNE--HFDLTVGP---SSIITIQVFDQKKFKKk 75

                          90
                  ....*....|
gi 528498301   78 -DKFIGSVKI 86
Cdd:cd08382    76 dQGFLGCVRI 85

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. 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: 176064 [Multi-domain] Cd Length: 126 Bit Score: 47.83 E-value: 4.26e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    3 RVVVESAKGI-PKKTIGVPDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLKGSPLDSSS--FIEVVVKDYETIGKDK 79
Cdd:cd08682     2 QVTVLQARGLlCKGKSGTNDAYVIIQLGKEKYSTSVKEKTTSPVWKEECSFELPGLLSGNGNraTLQLTVMHRNLLGLDK 81

                          90
                  ....*....|....*...
gi 528498301   80 FIGSVKISLKELAAGQTR 97
Cdd:cd08682    82 FLGQVSIPLNDLDEDKGR 99

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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: 176027 [Multi-domain] Cd Length: 122 Bit Score: 47.67 E-value: 4.39e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTIGVPDPIAGIIFRGE-----KKKTKAIDKELNPVWNEIIEFDlkGSPLD--SSSFIEVVVKDYET 74
Cdd:cd08381    15 LFVMVMHAKNLPLLDGSDPDPYVKTYLLPDpqkttKRKTKVVRKTRNPTFNEMLVYD--GLPVEdlQQRVLQVSVWSHDS 92

                          90
                  ....*....|....*..
gi 528498301   75 IGKDKFIGSVKISLKEL 91
Cdd:cd08381    93 LVENEFLGGVCIPLKKL 109

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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: 175996 [Multi-domain] Cd Length: 127 Bit Score: 47.65 E-value: 4.75e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1536 ESCPQECL-VRIHiiRCLDLQPKDNNGMCDPYIKISL---GRKTIDDRDHYKPNTLNPDFGRVFELNCYIP--QDKDLKI 1609
Cdd:cd04030    11 YSSQRQKLiVTVH--KCRNLPPCDSSDIPDPYVRLYLlpdKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEelKRRTLDV 88

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 528498301 1610 SV-YDYDLLSSDEKV-GETVIDLENRLLSrfgshcgipksycvSGVNQWRD 1658
Cdd:cd04030    89 AVkNSKSFLSREKKLlGQVLIDLSDLDLS--------------KGFTQWYD 125

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: 47.78 E-value: 5.59e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTI-GVPDPIAGIIF-----RGEKKKTKAIDKELNPVWNEIIEFDLKGSPLDSSSFIeVVVKDYETI 75
Cdd:cd08402    17 LTVVILEAKNLKKMDVgGLSDPYVKIHLmqngkRLKKKKTTIKKRTLNPYYNESFSFEVPFEQIQKVHLI-VTVLDYDRI 95

                          90
                  ....*....|....*...
gi 528498301   76 GKDKFIGSVKISLKELAA 93
Cdd:cd08402    96 GKNDPIGKVVLGCNATGA 113

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: 47.81 E-value: 5.76e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  365 TLSLKIYRAEDMPQMDDAfaqtvkhifggtddkkNLVDPFVEVN--FAGKKVCTK---IIEKNANPEWNQLIHLQVkfPS 439
Cdd:cd08404    16 RLTVVVLKARHLPKMDVS----------------GLADPYVKVNlyYGKKRISKKkthVKKCTLNPVFNESFVFDI--PS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 528498301  440 MCER---IKLTAFDWDRLSKNDVIGTTYLNLTKIASSGGEIEE 479
Cdd:cd08404    78 EELEdisVEFLVLDSDRVTKNEVIGRLVLGPKASGSGGHHWKE 120

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: 47.81 E-value: 5.81e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 528498301 1556 PK-DNNGMCDPYIKISL--GRKTI-DDRDHYKPNTLNPDFGR--VFELNCYIPQDKDLKISVYDYDLLSSDEKVGETVI 1628
Cdd:cd08404    28 PKmDVSGLADPYVKVNLyyGKKRIsKKKTHVKKCTLNPVFNEsfVFDIPSEELEDISVEFLVLDSDRVTKNEVIGRLVL 106

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: 46.87 E-value: 6.47e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1131 YHLRVYVYQARNLLPMDKDSF-SDPYVHVSFLHASK---TTEIIKSCLNPTWDQTLIfndieIYGDPQTIAYNpPNVVLE 1206
Cdd:cd04041     1 GVLVVTIHRATDLPKADFGTGsSDPYVTASFAKFGKplySTRIIRKDLNPVWEETWF-----VLVTPDEVKAG-ERLSCR 74

                          90
                  ....*....|....*
gi 528498301 1207 IYDSDQMGKDEAMGR 1221
Cdd:cd04041    75 LWDSDRFTADDRLGR 89

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176012 [Multi-domain] Cd Length: 110 Bit Score: 46.79 E-value: 6.82e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1140 ARNLlpMDKDSF--SDPYVHVSFLHASKT------TEIIKSCLNPTWD------QTLIFNDIEIygdpqtiaynppNVVL 1205
Cdd:cd04047     9 GKKL--DKKDFFgkSDPFLEISRQSEDGTwvlvyrTEVIKNTLNPVWKpftiplQKLCNGDYDR------------PIKI 74

                          90
                  ....*....|....*....
gi 528498301 1206 EIYDSDQMGKDEAMGRCTC 1224
Cdd:cd04047    75 EVYDYDSSGKHDLIGEFET 93

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: 47.26 E-value: 7.15e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  367 SLKIYRAEDMPqmddafaqtvkhifggTDDKKNLVDPFVE-VNFAGKKVC--TKIIEKNANPEWNQLIHLQVKFPSMCEr 443
Cdd:cd04043     4 TIRIVRAENLK----------------ADSSNGLSDPYVTlVDTNGKRRIakTRTIYDTLNPRWDEEFELEVPAGEPLW- 66

                          90       100
                  ....*....|....*....|....*
gi 528498301  444 IKLTAFDWDRLSKNDVIGTTYLNLT 468
Cdd:cd04043    67 ISATVWDRSFVGKHDLCGRASLKLD 91

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: 46.91 E-value: 7.16e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  366 LSLKIYRAEDMPQMDdafaqtvkhiFGGTDDkknlvdPFVEVNFAGKKVCTKIIEKNANPEWNQLIHLQVKfpSMCERIK 445
Cdd:cd08377     3 LQVKVIRASGLAAAD----------IGGKSD------PFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIK--DIHDVLE 64

                          90
                  ....*....|....*.
gi 528498301  446 LTAFDWDRLSKNDVIG 461
Cdd:cd08377    65 VTVYDEDKDKKPEFLG 80

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 47.37 E-value: 7.47e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSfSDPYVHVSFLHASKT----TEIIKSCLNPTWDQTLIFNDIEIYGDPQTIAYNPPN------ 1202
Cdd:cd08675     1 LSVRVLECRDLALKSNGT-CDPFARVTLNYSSKTdtkrTKVKKKTNNPRFDEAFYFELTIGFSYEKKSFKVEEEdlekse 79

                          90       100
                  ....*....|....*....|....
gi 528498301 1203 VVLEIYDSDQMGKDEAMGRCTCPP 1226
Cdd:cd08675    80 LRVELWHASMVSGDDFLGEVRIPL 103

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. 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: 176004 [Multi-domain] Cd Length: 108 Bit Score: 46.09 E-value: 1.17e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528498301  401 VDPFVEVNFaGKKVC-TKIIEKNANPEWNQLIHLQVKFPSMCERIKLTAFDWDRLSKNDVIGTTYLNLTKIA 471
Cdd:cd04039    26 MDPFVIISF-GRRVFrTSWRRHTLNPVFNERLAFEVYPHEKNFDIQFKVLDKDKFSFNDYVATGSLSVQELL 96

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: 46.03 E-value: 1.18e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1128 SFSYHLRVYVYQARNLlpmdKDSFSDPYVHVSFLHASKTTEIIKSCLNPTWDQTLIFNdieIYGDPQTIAYNPpnVVLEI 1207
Cdd:cd04011     1 PQDFQVRVRVIEARQL----VGGNIDPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFN---FHESPDELFDKI--IKISV 71

                          90
                  ....*....|...
gi 528498301 1208 YDSDQMGKDEAMG 1220
Cdd:cd04011    72 YDSRSLRSDTLIG 84

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: 46.39 E-value: 1.22e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1544 VRIHIIRCLDLQPKDN-NGMCDPYIKISLGRKTIDDRDHYKPNTLNPDFGRVFelncYIP----QDKdLKISVYDYDLLS 1618
Cdd:cd04044     4 LAVTIKSARGLKGSDIiGGTVDPYVTFSISNRRELARTKVKKDTSNPVWNETK----YILvnslTEP-LNLTVYDFNDKR 78

                          90
                  ....*....|...
gi 528498301 1619 SDEKVGETVIDLE 1631
Cdd:cd04044    79 KDKLIGTAEFDLS 91

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. 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 and this is indeed the case here. 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: 176035 [Multi-domain] Cd Length: 124 Bit Score: 46.47 E-value: 1.31e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  197 ALANKPQDFQIRIRVIEGRQLP-----GNNIKPVAKVSVCG--QTHRTRIRRGNNPFFDEIFSYNvNMLPSELFDESIMI 269
Cdd:cd08389     8 AFEYDPSARKLTVTVIRAQDIPtkdrgGASSWQVHLVLLPSkkQRAKTKVQRGPNPVFNETFTFS-RVEPEELNNMALRF 86

                          90       100
                  ....*....|....*....|..
gi 528498301  270 RVYNASSLRADSLMGE--FKLD 289
Cdd:cd08389    87 RLYGVERMRKERLIGEkvVPLS 108

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: 46.49 E-value: 1.32e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1546 IHIIRCLDLQPKDNNGMCDPYIKISLG---RKTIDDRDHYKPNTLNPDFGR--VFELNcyiPQDKD--LKISVYDYDLLS 1618
Cdd:cd04026    17 VEVREAKNLIPMDPNGLSDPYVKLKLIpdpKNETKQKTKTIKKTLNPVWNEtfTFDLK---PADKDrrLSIEVWDWDRTT 93


                  ....*.
gi 528498301 1619 SDEKVG 1624
Cdd:cd04026    94 RNDFMG 99

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: 46.48 E-value: 1.34e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  211 VIEGRQLPGNNIK--PVAKVSVCGQTHRTRIRRG-NNPFFDEIFSYNVNMLPSElfDESIMIRVYNASSLRADSLMGEFK 287
Cdd:cd08373     2 VVSLKNLPGLKGKgdRIAKVTFRGVKKKTRVLENeLNPVWNETFEWPLAGSPDP--DESLEIVVKDYEKVGRNRLIGSAT 79


                  ..
gi 528498301  288 LD 289
Cdd:cd08373    80 VS 81

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: 46.12 E-value: 1.39e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSF----LHASKTteiIKSCLNPTWDQTLIFNdIEIYGDPqtiaynppnVVLEIY 1208
Cdd:cd04042     2 LDIHLKEGRNLAARDRGGTSDPYVKFKYggktVYKSKT---IYKNLNPVWDEKFTLP-IEDVTQP---------LYIKVF 68

                          90
                  ....*....|....*
gi 528498301 1209 DSDQMGKDEAMGRCT 1223
Cdd:cd04042    69 DYDRGLTDDFMGSAF 83

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: 46.10 E-value: 1.45e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1140 ARNLLPMDKDSFSDPYVHVSFLHASKTTEIIKSCLNPTWDQTLifnDIEIYGDPQTIaynppnvvLEI--YDSDQMGKDE 1217
Cdd:cd08376     9 GKNLPPMDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQF---DLHLFDDQSQI--------LEIevWDKDTGKKDE 77


                  ....*
gi 528498301 1218 AMGRC 1222
Cdd:cd08376    78 FIGRC 82

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: 45.63 E-value: 1.51e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    1 MLRVVVESAKGIPKKTIGV-PDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFdLKGSPLDSSsfIEVVVKDYETigkDK 79
Cdd:cd04050     1 LLFVYLDSAKNLPLAKSTKePSPYVELTVGKTTQKSKVKERTNNPVWEEGFTF-LVRNPENQE--LEIEVKDDKT---GK 74

                          90
                  ....*....|..
gi 528498301   80 FIGSVKISLKEL 91
Cdd:cd04050    75 SLGSLTLPLSEL 86

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: 46.38 E-value: 1.52e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIP---KKTIGvpDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFD---LKGSPLDSSS-----FIEVVvk 70
Cdd:cd04017     3 LRAYIYQARDLLaadKSGLS--DPFARVSFLNQSQETEVIKETLSPTWDQTLIFDeveLYGSPEEIAQnpplvVVELF-- 78

                          90       100
                  ....*....|....*....|....*..
gi 528498301   71 DYETIGKDKFIG------SVKISLKEL 91
Cdd:cd04017    79 DQDSVGKDEFLGrsvakpLVKLDLEED 105

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: 46.09 E-value: 1.81e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528498301  402 DPFVEVNFAGKKVCTKIIEKNANPEWNQLI--HLQVKfPSMCERIKLTAFDWDRLSKNDVIGTTYLNLTKIASSG 474
Cdd:cd08373    16 DRIAKVTFRGVKKKTRVLENELNPVWNETFewPLAGS-PDPDESLEIVVKDYEKVGRNRLIGSATVSLQDLVSEG 89

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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: 175987 [Multi-domain] Cd Length: 162 Bit Score: 46.55 E-value: 2.21e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFL----HASK-TTEIIKSCLNPTWDQTLIFNDI 1187
Cdd:cd04020    29 LHVWVKEAKNLPALKSGGTSDSFVKCYLLpdksKKSKqKTPVVKKSVNPVWNHTFVYDGV 88

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: 45.75 E-value: 2.27e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1132 HLRVYVYQARNLLPMDKDSFSDPYVHVSFLHASKTTEIIKSCLNPTWDQTLIFNDIEIYGdpqtiaynppnvVLE--IYD 1209
Cdd:cd08377     2 FLQVKVIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYKTLNPEWNKIFTFPIKDIHD------------VLEvtVYD 69

                          90
                  ....*....|....*.
gi 528498301 1210 SDQMGKDEAMGRCTCP 1225
Cdd:cd08377    70 EDKDKKPEFLGKVAIP 85

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: 45.33 E-value: 3.55e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528498301  396 DKKNLVDPFVEVNF-----AGKKVCTKIIEKNANPEWNQLIHLQVKFPSMCERIKLTAFDWDRLSKNDVIG 461
Cdd:cd04026    29 DPNGLSDPYVKLKLipdpkNETKQKTKTIKKTLNPVWNETFTFDLKPADKDRRLSIEVWDWDRTTRNDFMG 99

C2 domain second 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 second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176024 [Multi-domain] Cd Length: 121 Bit Score: 45.00 E-value: 4.15e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 528498301   32 KKKTKAIDKELNPVWNEIIEFDlKGSPldSSSFIEVVVKDYETIgKDKFIGSVKISLKE 90
Cdd:cd08378    29 KGSTKAIERTSNPEWNQVFAFS-KDRL--QGSTLEVSVWDKDKA-KDDFLGGVCFDLSE 83

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: 45.10 E-value: 4.28e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  365 TLSLKIYRAEDMPQMDdafaqtvkhiFGGTDDkknlvdPFVEV--NFAGKKV---CTKIIEKNANPEWNQLIHLQVKFps 439
Cdd:cd08405    16 RITVNIIKARNLKAMD----------INGTSD------PYVKVwlMYKDKRVekkKTVIKKRTLNPVFNESFIFNIPL-- 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 528498301  440 mcERIKLTAF-----DWDRLSKNDVIGTTYL 465
Cdd:cd08405    78 --ERLRETTLiitvmDKDRLSRNDLIGKIYL 106

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

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 44.84 E-value: 5.70e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1542 CLVRIHII--RCLDLQPKDNNGMCDPYIKISL-G----------RKTIDDrdhykpNTLNPDFGRVFELNCYIPQDKDLK 1608
Cdd:cd00275     2 LTLTIKIIsgQQLPKPKGDKGSIVDPYVEVEIhGlpaddsakfkTKVVKN------NGFNPVWNETFEFDVTVPELAFLR 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 528498301 1609 ISVYDYDlLSSDEKVGETVIDLEN--------RLLSRFGS 1640
Cdd:cd00275    76 FVVYDED-SGDDDFLGQACLPLDSlrqgyrhvPLLDSKGE 114

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: 44.55 E-value: 6.03e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  364 ATLSLKIYRAEDMPQMDDAfaqtvkhifggtddkkNLVDPFVEVNF-----AGKKVCTKIIEKNANPEWNQ-LIHLQVKF 437
Cdd:cd04031    16 SQLIVTVLQARDLPPRDDG----------------SLRNPYVKVYLlpdrsEKSKRRTKTVKKTLNPEWNQtFEYSNVRR 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 528498301  438 PSMCER-IKLTAFDWDRLSKNDVIGTTYLNL 467
Cdd:cd04031    80 ETLKERtLEVTVWDYDRDGENDFLGEVVIDL 110

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. 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 synaptotagmin1. 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: 176063 [Multi-domain] Cd Length: 118 Bit Score: 44.16 E-value: 6.22e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIP-KKTIGVPDPIAGIIFRGEKKKTKAIDKE-LNPVWNEIIEFDLKGsplDSSSFIEVVVKDyETIGKDK 79
Cdd:cd08681     3 LVVVVLKARNLPnKRKLDKQDPYCVLRIGGVTKKTKTDFRGgQHPEWDEELRFEITE---DKKPILKVAVFD-DDKRKPD 78

                          90
                  ....*....|.
gi 528498301   80 FIGSVKISLKE 90
Cdd:cd08681    79 LIGDTEVDLSP 89

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: 44.54 E-value: 6.64e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGI-PKKTIGVPDPIAGI------IFRG-EKKKTKAIDKELNPVWNEIIEFDLkgSPLDSS---SFIEVVVK 70
Cdd:cd04009    18 LRVEILNARNLlPLDSNGSSDPFVKVellprhLFPDvPTPKTQVKKKTLFPLFDESFEFNV--PPEQCSvegALLLFTVK 95

                          90       100
                  ....*....|....*....|.
gi 528498301   71 DYETIGKDKFIGSVKISLKEL 91
Cdd:cd04009    96 DYDLLGSNDFEGEAFLPLNDI 116

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: 43.83 E-value: 7.64e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  366 LSLKIYRAEDMPQMDDAfaqtvkhifggtddkKNLVDPFVEVNFAGKKVCTKIIEKNANPEWNQLI--------HLQVkf 437
Cdd:cd08688     1 LKVRVVAARDLPVMDRS---------------SDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNSEWfrfevddeELQD-- 63

                          90       100       110
                  ....*....|....*....|....*....|.
gi 528498301  438 psmcERIKLTAFDWDRLSKNDVIGTTYLNLT 468
Cdd:cd08688    64 ----EPLQIRVMDHDTYSANDAIGKVYIDLN 90

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: 44.93 E-value: 7.68e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 528498301   20 PDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLKGSPLDSSsfIEVVVKDYETIGKDKFIGSVKISLKELAA 93
Cdd:cd04018    35 VDPYVEVSFAGQKVKTSVKKNSYNPEWNEQIVFPEMFPPLCER--IKIQIRDWDRVGNDDVIGTHFIDLSKISN 106

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

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 44.07 E-value: 8.63e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  207 IRIRVIEGRQLP------GNNIKPVAKVSVCG------QTHRTRIRRGN--NPFFDEIFSYNVNmlpselFDESIMIR-- 270
Cdd:cd00275     4 LTIKIISGQQLPkpkgdkGSIVDPYVEVEIHGlpaddsAKFKTKVVKNNgfNPVWNETFEFDVT------VPELAFLRfv 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 528498301  271 VYNASSLRaDSLMGE--FKLDV---GY----VYDETGHAI 301
Cdd:cd00275    78 VYDEDSGD-DDFLGQacLPLDSlrqGYrhvpLLDSKGEPL 116

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: 44.10 E-value: 1.02e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKG-IPKKTIGVPDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLKGSP-------LDSSSFIEVVVKDYE 73
Cdd:cd04027     3 ISITVVCAQGlIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSSdrikvrvWDEDDDIKSRLKQKF 82

                          90
                  ....*....|....*....
gi 528498301   74 TIGKDKFIGSVKISLKELA 92
Cdd:cd04027    83 TRESDDFLGQTIIEVRTLS 101

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. 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 of this cd have a type-II topology.

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 43.79 E-value: 1.02e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLHAS---KTTEIIKSCLNPTWDQTLIFndieiygdpqTIAYNPPNvVLEI-- 1207
Cdd:cd04036     2 LTVRVLRATNITKGDLLSTPDCYVELWLPTASdekKRTKTIKNSINPVWNETFEF----------RIQSQVKN-VLELtv 70

                          90
                  ....*....|
gi 528498301 1208 YDSDQMGKDE 1217
Cdd:cd04036    71 MDEDYVMDDH 80

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: 43.80 E-value: 1.16e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301   34 KTKAIDKELNPVWNEiiEFDLkgsPLDS-SSFIEVVVKDYETIGKDKFIGSVKISLKELAAGQTRSLASKNT-PLINEKK 111
Cdd:cd04042    36 KSKTIYKNLNPVWDE--KFTL---PIEDvTQPLYIKVFDYDRGLTDDFMGSAFVDLSTLELNKPTEVKLKLEdPNSDEDL 110

                          90
                  ....*....|
gi 528498301  112 QEIGATINLT 121
Cdd:cd04042   111 GYISLVVTLT 120

C2 domain second 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 second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 43.36 E-value: 1.22e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 528498301   15 KTIGVPDPIAGIIFRGEK-KKTKAIDKELNPVWNEIIEFDLKgsplD-SSSFIEVVVKDYEtIGKDKFIGSVKISLKEL 91
Cdd:cd04052     8 SKTGLLSPYAELYLNGKLvYTTRVKKKTNNPSWNASTEFLVT----DrRKSRVTVVVKDDR-DRHDPVLGSVSISLNDL 81

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: 43.42 E-value: 1.29e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  396 DKKNLVDPFVEVNFAGKKVC-TKIIEKNANPEWNQLIHLQVKFPSMCERIKLtaFDWDRLSKNDVIGTTYLNLTKiassg 474
Cdd:cd04042    16 DRGGTSDPYVKFKYGGKTVYkSKTIYKNLNPVWDEKFTLPIEDVTQPLYIKV--FDYDRGLTDDFMGSAFVDLST----- 88

                          90
                  ....*....|...
gi 528498301  475 gEIEETPSENGLP 487
Cdd:cd04042    89 -LELNKPTEVKLK 100

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: 43.71 E-value: 1.37e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1542 CLVRIHIIRCLDLQPKDNNGMCDPYIKISLGRktIDDRDHYKPNTLNPDFGRVFELNCYIPQDKdLKISVYD--YDLLS- 1618
Cdd:cd04027     1 AKISITVVCAQGLIAKDKTGTSDPYVTVQVGK--TKKRTKTIPQNLNPVWNEKFHFECHNSSDR-IKVRVWDedDDIKSr 77

                          90       100
                  ....*....|....*....|....*.
gi 528498301 1619 --------SDEKVGETVIDLenRLLS 1636
Cdd:cd04027    78 lkqkftreSDDFLGQTIIEV--RTLS 101

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

Pssm-ID: 176003 [Multi-domain] Cd Length: 145 Bit Score: 43.85 E-value: 1.53e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    1 MLRVVVESAKGIPKKTIGVPDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLKgSPLDSssfIEVVVKDYETIGKDKF 80
Cdd:cd04038     3 LLKVRVVRGTNLAVRDFTSSDPYVVLTLGNQKVKTRVIKKNLNPVWNEELTLSVP-NPMAP---LKLEVFDKDTFSKDDS 78

                          90
                  ....*....|...
gi 528498301   81 IGSVKISLKELAA 93
Cdd:cd04038    79 MGEAEIDLEPLVE 91

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: 43.41 E-value: 1.56e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLHASK---TTEIIKSCLNPTWDQTLIFNdieiygdpqtiayNPPN------V 1203
Cdd:cd08385    18 LTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKkkfETKVHRKTLNPVFNETFTFK-------------VPYSelgnktL 84

                          90       100
                  ....*....|....*....|..
gi 528498301 1204 VLEIYDSDQMGKDEAMGRCTCP 1225
Cdd:cd08385    85 VFSVYDFDRFSKHDLIGEVRVP 106

C2 domain second repeat present in Synaptotagmins 3, 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 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 43.65 E-value: 1.65e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301   17 IGVPDPIAGIIF-----RGEKKKTKAIDKELNPVWNEIIEFDLKGSPLDSSSFIeVVVKDYETIGKDKFIGSVKISlkEL 91
Cdd:cd08403    32 TGFSDPYVKVSLmcegrRLKKKKTSVKKNTLNPTYNEALVFDVPPENVDNVSLI-IAVVDYDRVGHNELIGVCRVG--PN 108


                  ....*.
gi 528498301   92 AAGQTR 97
Cdd:cd08403   109 ADGQGR 114

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: 43.31 E-value: 1.73e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTI--GVPDPIAGIIFRGEKK--KTKAIDKELNPVWNEIIEFDLkgspldsSSFIEVV---VKDYET 74
Cdd:cd04044     4 LAVTIKSARGLKGSDIigGTVDPYVTFSISNRRElaRTKVKKDTSNPVWNETKYILV-------NSLTEPLnltVYDFND 76

                          90
                  ....*....|....*..
gi 528498301   75 IGKDKFIGSVKISLKEL 91
Cdd:cd04044    77 KRKDKLIGTAEFDLSSL 93

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: 42.68 E-value: 1.81e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1544 VRIHIIRCLDLQPKD-NNGMCDPYIKISLGrKTIDDRDHYKpNTLNPDFGR---VFELNCYIPQDKDLKISVYDYDLLSS 1619
Cdd:cd08688     1 LKVRVVAARDLPVMDrSSDLTDAFVEVKFG-STTYKTDVVK-KSLNPVWNSewfRFEVDDEELQDEPLQIRVMDHDTYSA 78

                          90       100
                  ....*....|....*....|...
gi 528498301 1620 DEKVGETVIDLeNRLLSRFGSHC 1642
Cdd:cd08688    79 NDAIGKVYIDL-NPLLLKDSVSQ 100

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: 43.30 E-value: 2.06e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  389 HIFGGTD----DKKNLVDPFVEVNFAGKKVCTKIIEKNANPEWNQLIhlqvKFPS--MCERIKLTA----------FDWD 452
Cdd:cd04017     6 YIYQARDllaaDKSGLSDPFARVSFLNQSQETEVIKETLSPTWDQTL----IFDEveLYGSPEEIAqnpplvvvelFDQD 81

                          90
                  ....*....|.
gi 528498301  453 RLSKNDVIGTT 463
Cdd:cd04017    82 SVGKDEFLGRS 92

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: 42.92 E-value: 2.24e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    3 RVVVESAKGI-PKKTIGVPDPIaGIIFRGEKK---KTKAIDKELNPVWNEIIEFDLKgspLDSSSFIEVVVKDYETIGKD 78
Cdd:cd04037     3 RVYVVRARNLqPKDPNGKSDPY-LKIKLGKKKindRDNYIPNTLNPVFGKMFELEAT---LPGNSILKISVMDYDLLGSD 78

                          90
                  ....*....|
gi 528498301   79 KFIGSVKISL 88
Cdd:cd04037    79 DLIGETVIDL 88

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: 43.11 E-value: 2.40e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528498301  388 KHIFGGTDD--KKNLVDPFV--EVNfagkKVCTKIIEKNANPEWNQLIHLQVKfPSMCeRIKLTAFDWDRLSKNDVIG 461
Cdd:cd04033    15 KDIFGASDPyvKISLYDPDGngEID----SVQTKTIKKTLNPKWNEEFFFRVN-PREH-RLLFEVFDENRLTRDDFLG 86

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: 42.25 E-value: 2.46e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  365 TLSLKIYRAEDMPQMDdafAQTVKHifggtddkknlvDPFVEVNFA--GKKV-CTKIIEKNANPEWNQLIHLQVkFPSMC 441
Cdd:cd04041     2 VLVVTIHRATDLPKAD---FGTGSS------------DPYVTASFAkfGKPLySTRIIRKDLNPVWEETWFVLV-TPDEV 65

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 528498301  442 ---ERIKLTAFDWDRLSKNDVIGTTYLNLTKIASSGG 475
Cdd:cd04041    66 kagERLSCRLWDSDRFTADDRLGRVEIDLKELIEDRN 102

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: 43.16 E-value: 2.60e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  365 TLSLKIYRAEDMPQMDdafaqtvkhiFGGtddkknLVDPFVEVNFA--GKKVCTK--IIEKNA-NPEWNQLIHLQVKFPS 439
Cdd:cd08402    16 KLTVVILEAKNLKKMD----------VGG------LSDPYVKIHLMqnGKRLKKKktTIKKRTlNPYYNESFSFEVPFEQ 79

                          90       100
                  ....*....|....*....|....
gi 528498301  440 McERIKL--TAFDWDRLSKNDVIG 461
Cdd:cd08402    80 I-QKVHLivTVLDYDRIGKNDPIG 102

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A 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: 176034 [Multi-domain] Cd Length: 128 Bit Score: 42.34 E-value: 3.35e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDS-FSDPYVHVSFL----HASKTtEIIKSCLNPTWDQTLIFNDIEiYGDPQTIAYNppNVVLEI 1207
Cdd:cd08388    18 LLVNIIECRDLPAMDEQSgTSDPYVKLQLLpekeHKVKT-RVLRKTRNPVYDETFTFYGIP-YNQLQDLSLH--FAVLSF 93

                          90
                  ....*....|....*...
gi 528498301 1208 ydsDQMGKDEAMGRCTCP 1225
Cdd:cd08388    94 ---DRYSRDDVIGEVVCP 108

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 42.42 E-value: 3.41e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1545 RIHIIRCLDLQPKD-NNGMCDPYIKISL--------GRKTiddrdHYKPNTLNPDFGRV--FELNCYIPQDKDLKISVYD 1613
Cdd:cd08393    18 HVHVIQCQDLAAADpKKQRSDPYVKTYLlpdksnrgKRKT-----SVKKKTLNPVFNETlrYKVEREELPTRVLNLSVWH 92

                          90
                  ....*....|....*...
gi 528498301 1614 YDLLSSDEKVGETVIDLE 1631
Cdd:cd08393    93 RDSLGRNSFLGEVEVDLG 110

C2A domain first 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 42.32 E-value: 3.53e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTI-GVPDPIAGIIF---RGEKKKTKAIDKELNPVWNEIIEFDlkGSPLDS--SSFIEVVVKDYETI 75
Cdd:cd08386    18 LTLKILKAVELPAKDFsGTSDPFVKIYLlpdKKHKLETKVKRKNLNPHWNETFLFE--GFPYEKlqQRVLYLQVLDYDRF 95

                          90       100
                  ....*....|....*....|.
gi 528498301   76 GKDKFIGSVKISLKELAAGQT 96
Cdd:cd08386    96 SRNDPIGEVSLPLNKVDLTEE 116

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 45.52 E-value: 4.10e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1546 IHIIRCLDLQPKDNNGMCDPYIKISLGRKTIDDRDHYKpNTLNPDFGRVF--ELNCyipQDKD-LKISVYDYDLLSSDEK 1622
Cdd:COG5038  1044 IMLRSGENLPSSDENGYSDPFVKLFLNEKSVYKTKVVK-KTLNPVWNEEFtiEVLN---RVKDvLTINVNDWDSGEKNDL 1119

                          90
                  ....*....|..
gi 528498301 1623 VGETVIDLENRL 1634
Cdd:COG5038  1120 LGTAEIDLSKLE 1131

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: 41.86 E-value: 4.41e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1543 LVRIHIIRCLDLQPKDNN-GMCDPYIKISLGR--------KTIDDrdhykpnTLNPdfgrVFELNCYIPQDKD------- 1606
Cdd:cd04041     2 VLVVTIHRATDLPKADFGtGSSDPYVTASFAKfgkplystRIIRK-------DLNP----VWEETWFVLVTPDevkager 70

                          90       100
                  ....*....|....*....|....
gi 528498301 1607 LKISVYDYDLLSSDEKVGETVIDL 1630
Cdd:cd04041    71 LSCRLWDSDRFTADDRLGRVEIDL 94

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176013 [Multi-domain] Cd Length: 120 Bit Score: 41.79 E-value: 4.43e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  402 DPFVEV----NFAGKKVC---TKIIEKNANPEWNQLIHLQVKFPSmCERIKLTAFDWD----RLSKNDVIGTTYLNLTKI 470
Cdd:cd04048    22 DPFVVVyvktGGSGQWVEigrTEVIKNNLNPDFVTTFTVDYYFEE-VQKLRFEVYDVDskskDLSDHDFLGEAECTLGEI 100

                          90
                  ....*....|....*
gi 528498301  471 ASSGGEIEETPSENG 485
Cdd:cd04048   101 VSSPGQKLTLPLKGG 115

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: 41.52 E-value: 4.51e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIP--KKTIGVPDPIAGIIFRGEKKKTKAIDKELNPVWN------EIIEFDLKGSPLdsssfiEVVVKDYE 73
Cdd:cd08688     1 LKVRVVAARDLPvmDRSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNsewfrfEVDDEELQDEPL------QIRVMDHD 74

                          90
                  ....*....|....*...
gi 528498301   74 TIGKDKFIGSVKISLKEL 91
Cdd:cd08688    75 TYSANDAIGKVYIDLNPL 92

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: 42.62 E-value: 4.92e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528498301 1557 KDNNGMCDPYIKISLGRKTIddRDHYKPNTLNPDFGRVFELNCYIPQ-DKDLKISVYDYDLLSSDEKVGETVIDL 1630
Cdd:cd04018    29 GEKKELVDPYVEVSFAGQKV--KTSVKKNSYNPEWNEQIVFPEMFPPlCERIKIQIRDWDRVGNDDVIGTHFIDL 101

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: 41.95 E-value: 5.14e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFL-HASK----TTEIIKSCLNPTWDQTLIF 1184
Cdd:cd08384    15 LIVGIIRCVNLAAMDANGYSDPFVKLYLKpDAGKkskhKTQVKKKTLNPEFNEEFFY 71

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: 41.97 E-value: 5.20e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGIPKKTigVPDPIAgIIFRGEKK--KTKAidKE-LNPVWNEiiEFDLKGSPLDSSSFiEVVVKDYETIGKD 78
Cdd:cd08400     6 LQLNVLEAHKLPVKH--VPHPYC-VISLNEVKvaRTKV--REgPNPVWSE--EFVFDDLPPDVNSF-TISLSNKAKRSKD 77

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 528498301   79 KFIGSVKISLKELAAGQTRSLASKNTPLINEKKQEIG 115
Cdd:cd08400    78 SEIAEVTVQLSKLQNGQETDEWYPLSSASPLKGGEWG 114

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: 41.76 E-value: 5.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1132 HLRVYVYQARNLLPMDKDSFS--DPYVHVSFLHA------SKTTEIIKSC-LNPTWDQTLIFnDIeiygdpqtiaYNPPN 1202
Cdd:cd00275     3 TLTIKIISGQQLPKPKGDKGSivDPYVEVEIHGLpaddsaKFKTKVVKNNgFNPVWNETFEF-DV----------TVPEL 71

                          90       100
                  ....*....|....*....|....*
gi 528498301 1203 VVL--EIYDSDqMGKDEAMGRCTCP 1225
Cdd:cd00275    72 AFLrfVVYDED-SGDDDFLGQACLP 95

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: 41.99 E-value: 5.67e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  368 LKIYRAEDMPQmdDAFAQTVKHIFGGTD----DKKNLVDPFVEVNFAGKKVCTKIIEKNANPEWNQLIHLQVK---FPSM 440
Cdd:cd08375     1 EKAYLARSQRA--SGIGRLMVVIVEGRDlkpcNSNGKSDPYCEVSMGSQEHKTKVVSDTLNPKWNSSMQFFVKdleQDVL 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 528498301  441 CerikLTAFDWDRLSKNDVIGTTYLNLTKIASS 473
Cdd:cd08375    79 C----ITVFDRDFFSPDDFLGRTEIRVADILKE 107

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. 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: 175982 [Multi-domain] Cd Length: 158 Bit Score: 42.29 E-value: 6.06e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  365 TLSLKIYRAEDMPQMDdAFAQTVKHIF----GGTDDKKNL-----------VDPFVEVNFAGKKVC-TKIIEKNANPEWN 428
Cdd:cd04015     8 TLDVTIYEADNLPNMD-MFSEKLRRFFsklvGCSEPTLKRpsshrhvgkitSDPYATVDLAGARVArTRVIENSENPVWN 86

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 528498301  429 Q--LIHL-----QVKFpsmceRIKLtafdwdrlskNDVIGTTYLNLTKIA----SSGGEIE 478
Cdd:cd04015    87 EsfHIYCahyasHVEF-----TVKD----------NDVVGAQLIGRAYIPvedlLSGEPVE 132

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: 6.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1548 IIRCLDLQPKDNNGMCDPYIKISLGRKTIDDRDHYKpnTLNPDFGRVFELNCyipqdKD----LKISVYDYDLLSSDEKV 1623
Cdd:cd08377     7 VIRASGLAAADIGGKSDPFCVLELVNARLQTHTIYK--TLNPEWNKIFTFPI-----KDihdvLEVTVYDEDKDKKPEFL 79


                  ....*..
gi 528498301 1624 GETVIDL 1630
Cdd:cd08377    80 GKVAIPL 86

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: 41.47 E-value: 6.99e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1132 HLRVYVYQARNLLPMDKDS-FSDPYVHVSFL---HASKTTEIIKSCLNPTWDQTLIFNDIEIYGDPQTIAynppnvvLEI 1207
Cdd:cd08390    15 QLTVSLIKARNLPPRTKDVaHCDPFVKVCLLpdeRRSLQSKVKRKTQNPNFDETFVFQVSFKELQRRTLR-------LSV 87

                          90
                  ....*....|....*...
gi 528498301 1208 YDSDQMGKDEAMGRCTCP 1225
Cdd:cd08390    88 YDVDRFSRHCIIGHVLFP 105

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: 41.09 E-value: 7.81e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 528498301 1855 KEHFWSLDKTEFRIPPKLTIQIWDNDKFSLDDYLGTVELDLLHLI 1899
Cdd:cd04041    54 ETWFVLVTPDEVKAGERLSCRLWDSDRFTADDRLGRVEIDLKELI 98

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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: 175987 [Multi-domain] Cd Length: 162 Bit Score: 41.92 E-value: 9.04e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1527 PPRQFRELPESCPQECLVRIHIIRCLDLQPKDNNGMCDPYIKISLgrkTIDDRDHYK------PNTLNPDFGRVFELNCY 1600
Cdd:cd04020    12 PPESEGALKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYL---LPDKSKKSKqktpvvKKSVNPVWNHTFVYDGV 88

                          90       100
                  ....*....|....*....|....*..
gi 528498301 1601 IPQD-KD--LKISVYDYDLLSSDEKVG 1624
Cdd:cd04020    89 SPEDlSQacLELTVWDHDKLSSNDFLG 115

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 44.36 E-value: 9.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHvsFLHASK---TTEIIKSCLNPTWDQTlifNDIEIYGDPQTIaynppnVVLEIYD 1209
Cdd:COG5038  1042 LTIMLRSGENLPSSDENGYSDPFVK--LFLNEKsvyKTKVVKKTLNPVWNEE---FTIEVLNRVKDV------LTINVND 1110

                          90
                  ....*....|...
gi 528498301 1210 SDQMGKDEAMGRC 1222
Cdd:COG5038  1111 WDSGEKNDLLGTA 1123

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: 41.20 E-value: 9.82e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLlPMDKdsFSDPYVHVSF--LHASKTTeiIKSCLNPTWDQTLIFNDIeiygdpqtiaynPPNVV---LEI 1207
Cdd:cd08400     6 LQLNVLEAHKL-PVKH--VPHPYCVISLneVKVARTK--VREGPNPVWSEEFVFDDL------------PPDVNsftISL 68

                          90
                  ....*....|....*...
gi 528498301 1208 YDSDQMGKDEAMGRCTCP 1225
Cdd:cd08400    69 SNKAKRSKDSEIAEVTVQ 86

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176013 [Multi-domain] Cd Length: 120 Bit Score: 41.02 E-value: 1.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1548 IIRCLDLQPKDNNGMCDPYIKISLgrkTIDDRDHYK--------PNTLNPDFGRVFELNCYIPQDKDLKISVYDYDL--- 1616
Cdd:cd04048     6 SISCRNLLDKDVLSKSDPFVVVYV---KTGGSGQWVeigrteviKNNLNPDFVTTFTVDYYFEEVQKLRFEVYDVDSksk 82

                          90
                  ....*....|....*
gi 528498301 1617 -LSSDEKVGETVIDL 1630
Cdd:cd04048    83 dLSDHDFLGEAECTL 97

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: 41.11 E-value: 1.04e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  365 TLSLKIYRAEDMPQMDdafaqtvkhifggtddKKNLVDPFVEVNF---AGK--KVCTKIIEKNANPEWNQ-LIHLQVKFP 438
Cdd:cd04035    16 ALHCTIIRAKGLKAMD----------------ANGLSDPYVKLNLlpgASKatKLRTKTVHKTRNPEFNEtLTYYGITEE 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 528498301  439 SMCER-IKLTAFDWDRLSkNDVIGTTYLNLTK 469
Cdd:cd04035    80 DIQRKtLRLLVLDEDRFG-NDFLGETRIPLKK 110

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 41.20 E-value: 1.18e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  207 IRIRVIEGRQLP---GNNIKPVAKVSVCG----QTHRTRIRR-GNNPFFDEIF--------SYNVNMLPSELFD-ESIMI 269
Cdd:cd08675     1 LSVRVLECRDLAlksNGTCDPFARVTLNYssktDTKRTKVKKkTNNPRFDEAFyfeltigfSYEKKSFKVEEEDlEKSEL 80

                          90       100
                  ....*....|....*....|...
gi 528498301  270 RV--YNASSLRADSLMGEFKLDV 290
Cdd:cd08675    81 RVelWHASMVSGDDFLGEVRIPL 103

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, 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. RasA3 contains an N-terminal C2 domain, 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: 175977 [Multi-domain] Cd Length: 148 Bit Score: 41.23 E-value: 1.22e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  206 QIRIRVIEGRQLPGNN--IKPVAKVSVCG-----QTHRTRIRR-GNNPFFDEIFSYNVNMLPSELFDESIM--------- 268
Cdd:cd04010     1 KLSVRVIECSDLALKNgtCDPYASVTLIYsnkkqDTKRTKVKKkTNNPQFDEAFYFDVTIDSSPEKKQFEMpeedaekle 80

                          90       100
                  ....*....|....*....|..
gi 528498301  269 --IRVYNASSLRADSLMGEFKL 288
Cdd:cd04010    81 lrVDLWHASMGGGDVFLGEVRI 102

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: 40.79 E-value: 1.23e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 528498301  402 DPFVEVNF---AGKKVC--TKIIEKNANPEWNQLIHLQVKFPSMCER-IKLTAFDWDRLSKNDVIGTTYLNLT 468
Cdd:cd08384    35 DPFVKLYLkpdAGKKSKhkTQVKKKTLNPEFNEEFFYDIKHSDLAKKtLEITVWDKDIGKSNDYIGGLQLGIN 107

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. 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: 175998 [Multi-domain] Cd Length: 127 Bit Score: 40.71 E-value: 1.23e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1132 HLRVYVYQARNLLpmdKDSFS--DPYVHVSFLHASKTTEIIKSCLNPTWDQTLIFNDIEIY-GDPQTiaynppnvvLEIY 1208
Cdd:cd04032    29 TLTVTVLRATGLW---GDYFTstDGYVKVFFGGQEKRTEVIWNNNNPRWNATFDFGSVELSpGGKLR---------FEVW 96

                          90
                  ....*....|....*...
gi 528498301 1209 DSDQMGKDEAMGRCTCPP 1226
Cdd:cd04032    97 DRDNGWDDDLLGTCSVVP 114

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A 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: 176034 [Multi-domain] Cd Length: 128 Bit Score: 40.80 E-value: 1.26e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1545 RIHIIRCLDLQPKD-NNGMCDPYIKISLgrktIDDRDHYKP-----NTLNPDFGRVFELncY-IP----QDKDLKISVYD 1613
Cdd:cd08388    19 LVNIIECRDLPAMDeQSGTSDPYVKLQL----LPEKEHKVKtrvlrKTRNPVYDETFTF--YgIPynqlQDLSLHFAVLS 92

                          90
                  ....*....|....*..
gi 528498301 1614 YDLLSSDEKVGETVIDL 1630
Cdd:cd08388    93 FDRYSRDDVIGEVVCPL 109

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 40.88 E-value: 1.30e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 528498301   32 KKKTKAIDKELNPVWNEIIEFDLKGSPLDSSSFIeVVVKDYETIGKDKFIGSVKISLKELAAGQTR 97
Cdd:cd08393    54 KRKTSVKKKTLNPVFNETLRYKVEREELPTRVLN-LSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQ 118

C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. 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 and this is indeed the case here. 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: 176053 [Multi-domain] Cd Length: 138 Bit Score: 40.81 E-value: 1.37e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  187 VVRTTRKRQKAlANKPQDFQIRIRVIE--GRQLpgnnikpvakvSVCgqthRTRIRRGN-NPFFDEIFSYNVNMLpsELF 263
Cdd:cd08408    21 VIKGSNFKNLA-MNKAPDTYVKLTLLNsdGQEI-----------SKS----KTSIRRGQpDPEFKETFVFQVALF--QLS 82

                          90       100
                  ....*....|....*....|....*
gi 528498301  264 DESIMIRVYNASSLRADSLMGEFKL 288
Cdd:cd08408    83 EVTLMFSVYNKRKMKRKEMIGWFSL 107

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: 40.87 E-value: 1.43e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  402 DPFVEVNFAGKKVCTKIIEKNANPEWNQLIHLQVkFPSMCERIKLTAFDWDRLSKNDVIGTTYLNLtKIASSGGEIEETP 481
Cdd:cd04024    25 DPYAILSVGAQRFKTQTIPNTLNPKWNYWCEFPI-FSAQNQLLKLILWDKDRFAGKDYLGEFDIAL-EEVFADGKTGQSD 102


                  .
gi 528498301  482 S 482
Cdd:cd04024   103 K 103

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: 40.26 E-value: 1.48e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSfLHASKT--TEIIKSCLNPTWDQTL---IFNDIEIygdpqtiaynppnVVLEI 1207
Cdd:cd04045     3 LRLHIRKANDLKNLEGVGKIDPYVRVL-VNGIVKgrTVTISNTLNPVWDEVLyvpVTSPNQK-------------ITLEV 68

                          90
                  ....*....|....*
gi 528498301 1208 YDSDQMGKDEAMGRC 1222
Cdd:cd04045    69 MDYEKVGKDRSLGSV 83

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: 40.64 E-value: 1.78e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  209 IRVIEGRQLP----GNNIKPVAKVSVCGQ-----THRTRIRRGN-NPFFDEIFSYNVnmlPSELFDE-SIMIRVYNASSL 277
Cdd:cd00276    18 VVVLKARNLPpsdgKGLSDPYVKVSLLQGgkklkKKKTSVKKGTlNPVFNEAFSFDV---PAEQLEEvSLVITVVDKDSV 94

                          90       100
                  ....*....|....*....|..
gi 528498301  278 RADSLMGefKLDVGYVYDETGH 299
Cdd:cd00276    95 GRNEVIG--QVVLGPDSGGEEL 114

C2 domain first 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 second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 40.82 E-value: 1.81e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVVESAKGI-PKKTIGVPDP--IAGIIFRGEK---------------------------KKTKAIDKELNPVWNEIIE 51
Cdd:cd08676    30 LKVTVIEAKGLlAKDVNGFSDPycMLGIVPASRErnsekskkrkshrkkavlkdtvpaksiKVTEVKPQTLNPVWNETFR 109

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 528498301   52 FDLKGspLDSSSF-IEVVVKDyetigkDKFIGSVKISLKEL 91
Cdd:cd08676   110 FEVED--VSNDQLhLDIWDHD------DDFLGCVNIPLKDL 142

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: 40.24 E-value: 1.83e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 528498301  396 DKKNLVDPFVEVNFAGKKVCTKIIEKNANPEWNQLIHLQVKFPSmcERIKLTAFDWD 452
Cdd:cd04027    17 DKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHFECHNSS--DRIKVRVWDED 71

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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-I topology.

Pssm-ID: 176029 [Multi-domain] Cd Length: 117 Bit Score: 39.94 E-value: 1.98e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  208 RIRVIEGRQLPGN-------NIKpVAKVSVCgqthRTRIRRGNNPFFDEIFSYNVnmLPSELfdESIMIRVYNAS--SLR 278
Cdd:cd08383     3 RLRILEAKNLPSKgtrdpycTVS-LDQVEVA----RTKTVEKLNPFWGEEFVFDD--PPPDV--TFFTLSFYNKDkrSKD 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 528498301  279 ADSLMGEF---KLDVGYVYDEtghaimrkWLLLG--DPDDAVSG 317
Cdd:cd08383    74 RDIVIGKValsKLDLGQGKDE--------WFPLTpvDPDSEVQG 109

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: 39.87 E-value: 2.04e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    3 RVVVESAKGIPKKTIgvpDPIAGIIFRGEKKKTKAIDKELNPVWNEIIEFDLKGSPL---DSSSFIEVVvkDYETIGKDK 79
Cdd:cd04011     7 RVRVIEARQLVGGNI---DPVVKVEVGGQKKYTSVKKGTNCPFYNEYFFFNFHESPDelfDKIIKISVY--DSRSLRSDT 81


                  ....*....
gi 528498301   80 FIGSVKISL 88
Cdd:cd04011    82 LIGSFKLDV 90

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: 40.24 E-value: 2.19e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLHASKTTEIIKSCLNPTWDQTLIF 1184
Cdd:cd04027     3 ISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKKRTKTIPQNLNPVWNEKFHF 54

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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: 175987 [Multi-domain] Cd Length: 162 Bit Score: 40.77 E-value: 2.28e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 528498301  416 TKIIEKNANPEWN-QLIHLQVKFPSMCER-IKLTAFDWDRLSKNDVIGTTYLNLTKIASSGGEIE 478
Cdd:cd04020    68 TPVVKKSVNPVWNhTFVYDGVSPEDLSQAcLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVD 132

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: 39.95 E-value: 2.58e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  205 FQIRIRVIEGRQLPGNNIK---PVAKVSVCGQ-THRTRIRRG-NNPFFDEIFSYNVNmlPSELFDesimIRVYNASSLRA 279
Cdd:cd04021     2 SQLQITVESAKLKSNSKSFkpdPYVEVTVDGQpPKKTEVSKKtSNPKWNEHFTVLVT--PQSTLE----FKVWSHHTLKA 75

                          90
                  ....*....|
gi 528498301  280 DSLMGEFKLD 289
Cdd:cd04021    76 DVLLGEASLD 85

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 42.82 E-value: 2.62e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1544 VRIHIIRCLDLQPKDN--NGMCDPYIKISLGRKTIDdRDHYKPNTLNPDFGRVFelncYIP---QDKDLKISVYDYDLLS 1618
Cdd:COG5038   438 VEVKIKSAEGLKKSDStiNGTVDPYITVTFSDRVIG-KTRVKKNTLNPVWNETF----YILlnsFTDPLNLSLYDFNSFK 512

                          90
                  ....*....|..
gi 528498301 1619 SDEKVGETVIDL 1630
Cdd:COG5038   513 SDKVVGSTQLDL 524

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: 39.48 E-value: 2.70e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1294 VQLTAIEilawglrnmkAYQLAAV-SSPSLVVECGGQIIQTAtiknIKKNPNFP--GSVLFLKVLLPKDEMYTPPIVVKV 1370
Cdd:cd04011     6 VRVRVIE----------ARQLVGGnIDPVVKVEVGGQKKYTS----VKKGTNCPfyNEYFFFNFHESPDELFDKIIKISV 71

                          90       100
                  ....*....|....*....|....*.
gi 528498301 1371 IDHRPFGRKPVVGqctinsleEFRCD 1396
Cdd:cd04011    72 YDSRSLRSDTLIG--------SFKLD 89

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 39.87 E-value: 2.83e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1546 IHIIRCLDLQPKDNNGMCDPYIKISL--GRKTIDDRD-HYKPNTLNPDFGRVFELNcyIPQ----DKDLKISVYDYDLLS 1618
Cdd:cd08410    18 VDIIRAKQLLQTDMSQGSDPFVKIQLvhGLKLIKTKKtSCMRGTIDPFYNESFSFK--VPQeeleNVSLVFTVYGHNVKS 95

                          90
                  ....*....|
gi 528498301 1619 SDEKVGETVI 1628
Cdd:cd08410    96 SNDFIGRIVI 105

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: 40.02 E-value: 2.86e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 528498301   32 KKKTKAIDKELNPVWNEIIEFDLKGSPLdSSSFIEVVVKDYEtIGK-DKFIGSVKISL 88
Cdd:cd08384    51 KHKTQVKKKTLNPEFNEEFFYDIKHSDL-AKKTLEITVWDKD-IGKsNDYIGGLQLGI 106

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: 39.83 E-value: 2.93e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1545 RIHIIRCLDLQPKDNNGMCDPYIKISLGRKTIddRDHYKPNTLNP--DFGRVFElNCYIPQD-KDLK-------ISVYDY 1614
Cdd:cd04017     4 RAYIYQARDLLAADKSGLSDPFARVSFLNQSQ--ETEVIKETLSPtwDQTLIFD-EVELYGSpEEIAqnpplvvVELFDQ 80

                          90
                  ....*....|....
gi 528498301 1615 DLLSSDEKVGETVI 1628
Cdd:cd04017    81 DSVGKDEFLGRSVA 94

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176012 [Multi-domain] Cd Length: 110 Bit Score: 39.09 E-value: 3.17e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1549 IRCLDLQPKDNNGMCDPYIKISlgrKTIDD-------RDHYKPNTLNPDFgRVFELN----CYIPQDKDLKISVYDYDLL 1617
Cdd:cd04047     7 FSGKKLDKKDFFGKSDPFLEIS---RQSEDgtwvlvyRTEVIKNTLNPVW-KPFTIPlqklCNGDYDRPIKIEVYDYDSS 82

                          90       100
                  ....*....|....*....|....
gi 528498301 1618 SSDEKVGETVIDLENRLLSRFGSH 1641
Cdd:cd04047    83 GKHDLIGEFETTLDELLKSSPLEF 106

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 39.34 E-value: 3.47e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 528498301  236 RTRIRRGN-NPFFDEIFSYNVNMlpSELFDESIMIRVYNASSLRADSLMGEFKLDVG 291
Cdd:cd08393    56 KTSVKKKTlNPVFNETLRYKVER--EELPTRVLNLSVWHRDSLGRNSFLGEVEVDLG 110

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, 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. RasA3 contains an N-terminal C2 domain, 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: 175977 [Multi-domain] Cd Length: 148 Bit Score: 40.07 E-value: 3.48e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1546 IHIIRCLDLQPKdnNGMCDPYIKISL---GRKTIDDRDHYKPNTLNPDFGRVFELNCYIPQDKD---------------L 1607
Cdd:cd04010     4 VRVIECSDLALK--NGTCDPYASVTLiysNKKQDTKRTKVKKKTNNPQFDEAFYFDVTIDSSPEkkqfempeedaekleL 81

                          90       100       110
                  ....*....|....*....|....*....|....
gi 528498301 1608 KISVYDYDLLSSDEKVGETVIDLENRLLSRfGSH 1641
Cdd:cd04010    82 RVDLWHASMGGGDVFLGEVRIPLRGLDLQA-GSH 114

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: 39.55 E-value: 3.76e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    2 LRVVveSAKGI-PKKTIGVPDPIAGIIFRGEKK---KTKAIDKELNPVWNEiiEFDLKgSPLDSSSFIEVVV------KD 71
Cdd:cd04043     5 IRIV--RAENLkADSSNGLSDPYVTLVDTNGKRriaKTRTIYDTLNPRWDE--EFELE-VPAGEPLWISATVwdrsfvGK 79


                  ....*.
gi 528498301   72 YETIGK 77
Cdd:cd04043    80 HDLCGR 85

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

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 39.49 E-value: 4.07e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 528498301  396 DKKNLVDPFVEVN--FAGKKVC---TKIIEKNANPEWNQLIHLQVKFPSMCE-RIKLTAFDWDRLSKNDVIG 461
Cdd:cd00276    30 DGKGLSDPYVKVSllQGGKKLKkkkTSVKKGTLNPVFNEAFSFDVPAEQLEEvSLVITVVDKDSVGRNEVIG 101

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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-I topology.

Pssm-ID: 176029 [Multi-domain] Cd Length: 117 Bit Score: 39.17 E-value: 4.41e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1132 HLRVYVYQARNLLPmdkDSFSDPYVHVSF--LHASKTTEIIKscLNPTWDQTLIFNDIEIYGDPQTIAynppnvvLEIYD 1209
Cdd:cd08383     1 SLRLRILEAKNLPS---KGTRDPYCTVSLdqVEVARTKTVEK--LNPFWGEEFVFDDPPPDVTFFTLS-------FYNKD 68

                          90
                  ....*....|...
gi 528498301 1210 SDQMGKDEAMGRC 1222
Cdd:cd08383    69 KRSKDRDIVIGKV 81

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

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 39.24 E-value: 4.63e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 528498301  396 DKKNLVDPFVEVNFAGKKVCTKIIEKNANPEWNQLIHLQVKFPS 439
Cdd:cd04022    16 DGQGSSSAYVELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPS 59

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: 38.78 E-value: 4.74e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  395 DDKKNLVDPFVEVNFAGKKVCTKIIEKNANPEWNQLIHLQVkFPSMCERIKLTAFDWDRLSKNDVIGTTYLNLTKIassg 474
Cdd:cd08376    15 MDDNGLSDPYVKFRLGNEKYKSKVCSKTLNPQWLEQFDLHL-FDDQSQILEIEVWDKDTGKKDEFIGRCEIDLSAL---- 89


                  ....*.
gi 528498301  475 gEIEET 480
Cdd:cd08376    90 -PREQT 94

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

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 39.57 E-value: 4.78e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLHAS-KTTEIIKSCLNPTWDQTLIFndieiygdpqtIAYNP--PNVVLEIYD 1209
Cdd:cd04019     2 LRVTVIEAQDLVPSDKNRVPEVFVKAQLGNQVlRTRPSQTRNGNPSWNEELMF-----------VAAEPfeDHLILSVED 70

                          90       100
                  ....*....|....*....|..
gi 528498301 1210 SDQMGKDEAMGRCtcppVVKLN 1231
Cdd:cd04019    71 RVGPNKDEPLGRA----VIPLN 88

C2A domain first 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 38.85 E-value: 5.27e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 528498301 1133 LRVYVYQARNLLPMDKDSFSDPYVHVSFLHASK---TTEIIKSCLNPTWDQTLIF 1184
Cdd:cd08386    18 LTLKILKAVELPAKDFSGTSDPFVKIYLLPDKKhklETKVKRKNLNPHWNETFLF 72

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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: 176056 [Multi-domain] Cd Length: 123 Bit Score: 38.78 E-value: 5.66e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301   29 RGEKKKTKAIDKELNPVWNEIIEFDLKGSPLDSSSfIEVVVKDYETIGKDKFIGSVKISL 88
Cdd:cd08521    50 KQSKRKTSVKKNTTNPVFNETLKYHISKSQLETRT-LQLSVWHHDRFGRNTFLGEVEIPL 108

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: 38.81 E-value: 5.73e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 528498301  397 KKNLVDPFVEVNFAGKKVCTKIIEKNANPEWNQLIHLQVKfPSMCERIKLTAFDWDRlSKNDVIGTTYLNLTKIASSG 474
Cdd:cd08391    24 VKGKSDPYVIVRVGAQTFKSKVIKENLNPKWNEVYEAVVD-EVPGQELEIELFDEDP-DKDDFLGRLSIDLGSVEKKG 99

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 38.07 E-value: 6.74e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  1800 NMSDIYVKGWMPGmEEDKQKTDVHYRSLdgdgNFNWrfvfgfdylpaeqlclvsrKEHFwsldktEFRIPP----KLTIQ 1875
Cdd:pfam00168   20 GTSDPYVKVYLLD-GKQKKKTKVVKNTL----NPVW-------------------NETF------TFSVPDpenaVLEIE 69

                           90       100
                   ....*....|....*....|
gi 528498301  1876 IWDNDKFSLDDYLGTVELDL 1895
Cdd:pfam00168   70 VYDYDRFGRDDFIGEVRIPL 89

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. 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 of this cd have a type-II topology.

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 38.40 E-value: 6.82e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  386 TVKHIFGGTDDKKNLV---DPFVEVNF---AGKKVCTKIIEKNANPEWNQ----LIHLQVKfpsmcERIKLTAFDWDRLs 455
Cdd:cd04036     3 TVRVLRATNITKGDLLstpDCYVELWLptaSDEKKRTKTIKNSINPVWNEtfefRIQSQVK-----NVLELTVMDEDYV- 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 528498301  456 KNDVIGTTYLNLTKIasSGGEIEEtpsengLPSSFN-VDTTEAEVGFL 502
Cdd:cd04036    77 MDDHLGTVLFDVSKL--KLGEKVR------VTFSLNpQGKEELEVEFL 116

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: 38.76 E-value: 6.97e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  366 LSLKIYRAEDMPQMDDafaqtvkhifggtddkKNLVDPFVEVNFAGK-------KVCTKIIEKNANPEWNQ-----LIHL 433
Cdd:cd04009    18 LRVEILNARNLLPLDS----------------NGSSDPFVKVELLPRhlfpdvpTPKTQVKKKTLFPLFDEsfefnVPPE 81

                          90       100       110
                  ....*....|....*....|....*....|....
gi 528498301  434 QVKFPSMCerIKLTAFDWDRLSKNDVIGTTYLNL 467
Cdd:cd04009    82 QCSVEGAL--LLFTVKDYDLLGSNDFEGEAFLPL 113

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176012 [Multi-domain] Cd Length: 110 Bit Score: 37.93 E-value: 8.20e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301  391 FGGTD-DKKNLV---DPFVEV-----NFAGKKVC-TKIIEKNANPEWNQL-IHLQvkfpSMC----ER-IKLTAFDWDRL 454
Cdd:cd04047     7 FSGKKlDKKDFFgksDPFLEIsrqseDGTWVLVYrTEVIKNTLNPVWKPFtIPLQ----KLCngdyDRpIKIEVYDYDSS 82

                          90       100
                  ....*....|....*....|..
gi 528498301  455 SKNDVIGTTYLNLTKIASSGGE 476
Cdd:cd04047    83 GKHDLIGEFETTLDELLKSSPL 104

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. 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 of this cd have a type-II topology.

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 38.01 E-value: 9.56e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528498301    1 MLRVVVESAKGIPKK-TIGVPDPIAGIIFR---GEKKKTKAIDKELNPVWNEIIEFDLKGsplDSSSFIEVVVKDYETIG 76
Cdd:cd04036     1 LLTVRVLRATNITKGdLLSTPDCYVELWLPtasDEKKRTKTIKNSINPVWNETFEFRIQS---QVKNVLELTVMDEDYVM 77

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 528498301   77 KDKfIGSVKISLKELAAGQTRSLASKntplINEKKQE 113
Cdd:cd04036    78 DDH-LGTVLFDVSKLKLGEKVRVTFS----LNPQGKE 109