NCBI Conserved Domain Search

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: 291.15 E-value: 1.81e-95

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 498 KGELVVSLKYIPASKLPvggdRKKSKGGEGGELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLS 577
Cdd:cd04020   1 RGELKVALKYVPPESEG----ALKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVN 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 578 PHYNHTFVYNGVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGVGTGISNGEVVDWMDSTGEEVSLWQKMRQYPGSWAE 657
Cdd:cd04020  77 PVWNHTFVYDGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDWMDSTGEEILLWQKMLDNPNSWVE 156


                ....*.
gi 33301669 658 GTLQLR 663
Cdd:cd04020 157 GTLPLR 162

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; 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. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. 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: 175995 [Multi-domain] Cd Length: 125 Bit Score: 245.43 E-value: 2.25e-78

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 359 TGKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESL 438
Cdd:cd04029   1 SGEILFSLSYDYKTQSLNVHVKECRNLAYGDEAKKRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHSQ 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 33301669 439 LAQRTLQFSVWHHGRFGRNTFLGEAEVHMDSWKLDKKLDHCLPLH 483
Cdd:cd04029  81 LETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDSQHEECLPLH 125

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: 224.06 E-value: 3.28e-70

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd08521   1 GEIEFSLSYNYKTGSLEVHIKECRNLAYADEKKKRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYHISKSQL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLGEAEVHMDSWKLDKKLDHCLPL 482
Cdd:cd08521  81 ETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123

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: 166.84 E-value: 8.48e-49

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd08393   2 GSVQFALDYDPKLRELHVHVIQCQDLAAADPKKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREEL 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLGEAEVHMDSWKLDKKLDHCLPL 482
Cdd:cd08393  82 PTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQPTWYPL 124

C2 domain first repeat present in Synaptotagmin-like protein 3; 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. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176038 [Multi-domain] Cd Length: 128 Bit Score: 132.26 E-value: 3.49e-36

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 359 TGKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESL 438
Cdd:cd08392   1 TGEIEFALHYNFRTSCLEITIKACRNLAYGDEKKKKCHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADL 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 33301669 439 LAQRTLQFSVWHHGRFGRNTFLGEAEVHMDSWKLDKK 475
Cdd:cd08392  81 LSSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFEDT 117

FYVE-related domain found in synaptotagmin-like protein 4 (Slp4) and similar proteins; Slp4, also termed exophilin-2, or granuphilin, has been characterized as a regulator of the release of insulin granules from pancreatic beta-cells and dense core granules from PC12 neuronal cells by binding to Rab27A , and amylase granules from parotid gland acinar cells through interaction with syntaxin-2/3 in a Munc18-2-dependent manner on the apical plasma membrane. It can binds to syntaxin 2 in parotid acinar cells. It is also involved in granule transport by recruitment of the motor protein myosin Va. Moreover, it requires Rab8 to increase granule release in platelets. Slp4 contains an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains. The Slp homology domain (SHD) consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp4 are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.

Pssm-ID: 277303 Cd Length: 50 Bit Score: 99.47 E-value: 1.28e-25

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 33301669  58 YSDRTCARCQEGLGRLIPKSSTCVGCNHLVCRECRVLESNGSWRCKVCSK 107
Cdd:cd15764   1 YSERSCGRCQESLGRLSPKANQCRGCNHLVCRDCRAVRPNGSWVCSVCAK 50

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 99.32 E-value: 8.01e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669   373 QTLVIHVKECHQLAYADEAKKrSNPYVKTYLLPDKSrqgKRKTSIKRDTINPLYDETFRYEISESllAQRTLQFSVWHHG 452
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGT-SDPYVKVYLLDGKQ---KKKTKVVKNTLNPVWNETFTFSVPDP--ENAVLEIEVYDYD 74

                          90       100       110
                  ....*....|....*....|....*....|
gi 33301669   453 RFGRNTFLGEAEVHMDSWKLDKKLDHCLPL 482
Cdd:pfam00168  75 RFGRDDFIGEVRIPLSELDSGEGLDGWYPL 104

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 96.62 E-value: 7.29e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669   528 GELQVWIKEAKNLTAAKSGGTSDSFVKGYLLpmrNKASKRKTPVMKKTLSPHYNHTFVYNgvrLEDLQHMCLELTVWDRE 607
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAVLEIEVYDYD 74

                          90       100
                  ....*....|....*....|....*....
gi 33301669   608 PLASNDFLGGVRLGVGTGISNGEVVDWMD 636
Cdd:pfam00168  75 RFGRDDFIGEVRIPLSELDSGEGLDGWYP 103

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: 97.42 E-value: 8.39e-24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 528 GELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSPHYNHTFVYNgVRLEDLQHMCLELTVWDRE 607
Cdd:cd08384  13 RGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYD-IKHSDLAKKTLEITVWDKD 91

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 33301669 608 PLASNDFLGGVRLGVgtgisngevvdwmDSTGEEVSLWQKMRQYPG 653
Cdd:cd08384  92 IGKSNDYIGGLQLGI-------------NAKGERLRHWLDCLKNPD 124

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: 97.03 E-value: 1.01e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 361 KIAFSLKFEQKTQTLVIHVKECHQLAYADeAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLLA 440
Cdd:cd08384   1 KILVSLMYNTQRRGLIVGIIRCVNLAAMD-ANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLA 79

                        90       100
                ....*....|....*....|.
gi 33301669 441 QRTLQFSVWHHGRFGRNTFLG 461
Cdd:cd08384  80 KKTLEITVWDKDIGKSNDYIG 100

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: 95.78 E-value: 2.61e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 525 GEGGELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSPHYNHTFVYNGVRLEDLQHMCLELTVW 604
Cdd:cd04031  13 KVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRETLKERTLEVTVW 92

                        90       100
                ....*....|....*....|....*.
gi 33301669 605 DREPLASNDFLGGVRLGVGTGISNGE 630
Cdd:cd04031  93 DYDRDGENDFLGEVVIDLADALLDDE 118

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: 94.04 E-value: 8.10e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 498 KGELVVSLKYIPASKlpvggdrkkskggeggELQVWIKEAKNLTAAKS-GGTSDSFVKGYLLPMRNKASKRKTPVMKKTL 576
Cdd:cd08393   1 QGSVQFALDYDPKLR----------------ELHVHVIQCQDLAAADPkKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTL 64

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 33301669 577 SPHYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGVGT 624
Cdd:cd08393  65 NPVFNETLRYK-VEREELPTRVLNLSVWHRDSLGRNSFLGEVEVDLGS 111

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: 94.25 E-value: 8.40e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKRSNPYVKTYLLPDKSRQgkRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd08390   1 GRLWFSVQYDLEEEQLTVSLIKARNLPPRTKDVAHCDPFVKVCLLPDERRS--LQSKVKRKTQNPNFDETFVFQVSFKEL 78

                        90       100
                ....*....|....*....|....
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLGEA 463
Cdd:cd08390  79 QRRTLRLSVYDVDRFSRHCIIGHV 102

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: 93.90 E-value: 8.86e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 526 EGGELQVWIKEAKNLtAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSPHYNHTFVYNGVRLEDLQHMCLELTVWD 605
Cdd:cd08381  11 KNGTLFVMVMHAKNL-PLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQQRVLQVSVWS 89

                        90       100
                ....*....|....*....|....*....
gi 33301669 606 REPLASNDFLGGVRLGVGTGISNGEVVDW 634
Cdd:cd08381  90 HDSLVENEFLGGVCIPLKKLDLSQETEKW 118

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: 93.13 E-value: 1.60e-22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 359 TGKIAFSLKFEQKTQT-LVIHVKECHQLAYADeakkrSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYE-ISE 436
Cdd:cd08381   1 GGQVKLSISYKNGTLFvMVMHAKNLPLLDGSD-----PDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDgLPV 75

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 33301669 437 SLLAQRTLQFSVWHHGRFGRNTFLGeaEVHMDSWKLD 473
Cdd:cd08381  76 EDLQQRVLQVSVWSHDSLVENEFLG--GVCIPLKKLD 110

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: 92.08 E-value: 5.86e-22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYIPASklpvggdrkkskggegGELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSP 578
Cdd:cd08402   2 GDICFSLRYVPTA----------------GKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNP 65

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 33301669 579 HYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRLgvGTGISNGEVVDWMD 636
Cdd:cd08402  66 YYNESFSFE-VPFEQIQKVHLIVTVLDYDRIGKNDPIGKVVL--GCNATGAELRHWSD 120

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: 91.56 E-value: 6.34e-22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADeAKKRSNPYVKTYLLPDKSRqgKRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd08385   3 GKLQFSLDYDFQSNQLTVGIIQAADLPAMD-MGGTSDPYVKVYLLPDKKK--KFETKVHRKTLNPVFNETFTFKVPYSEL 79

                        90       100
                ....*....|....*....|....*...
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLGEAEVHM 467
Cdd:cd08385  80 GNKTLVFSVYDFDRFSKHDLIGEVRVPL 107

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: 91.54 E-value: 7.56e-22

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 358 VTGKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKRsNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRY-EISE 436
Cdd:cd04031   1 ITGRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSLR-NPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYsNVRR 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 33301669 437 SLLAQRTLQFSVWHHGRFGRNTFLGEAEVHMDSWKLDKKlDHCLPLH 483
Cdd:cd04031  80 ETLKERTLEVTVWDYDRDGENDFLGEVVIDLADALLDDE-PHWYPLQ 125

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: 89.64 E-value: 3.75e-21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 358 VTGKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKrSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISES 437
Cdd:cd04030   1 PLGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDI-PDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLE 79

                        90       100       110
                ....*....|....*....|....*....|
gi 33301669 438 LLAQRTLQFSVWHHGRF--GRNTFLGEAEV 465
Cdd:cd04030  80 ELKRRTLDVAVKNSKSFlsREKKLLGQVLI 109

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: 88.79 E-value: 8.33e-21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYIPASklpvggdrkkskggegGELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSP 578
Cdd:cd00276   1 GELLLSLSYLPTA----------------ERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNP 64

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33301669 579 HYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGVgtgisngevvdwmDSTGEEVSLWQKMRQYPG 653
Cdd:cd00276  65 VFNEAFSFD-VPAEQLEEVSLVITVVDKDSVGRNEVIGQVVLGP-------------DSGGEELEHWNEMLASPR 125

FYVE-type zinc finger; This FYVE-type zinc finger is found at the N-terminus of effector proteins including rabphilin-3A and regulating synaptic membrane exocytosis protein 2.

Pssm-ID: 426716 Cd Length: 118 Bit Score: 86.27 E-value: 4.41e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669     8 SFLSEMERDLILGVLQRDEELRKADEKRIRRLKNEL-LEIKRKGAKRGSQHYSDRTCARCQEGLGRLIPKSSTCVGCNHL 86
Cdd:pfam02318   1 SKLTDEEAEHVWEVVQRDFDLRKKEEERLGELKGKLdKESSKRELLGNQAHLGETHCIRCLQPFGFLVNSKRQCLDCRKN 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 33301669    87 VCRECRVLESN-GSWRCKVCSKEIELKKATGDWFYD 121
Cdd:pfam02318  81 VCKKCGVYNKPeQGWLCDPCSEARELKKGSLEWFYK 116

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: 85.01 E-value: 1.39e-19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 526 EGGELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSPHYNHTFVYNgVRLEDLqHMCLELTVWD 605
Cdd:cd04026  11 KDNKLTVEVREAKNLIPMDPNGLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFD-LKPADK-DRRLSIEVWD 88

                        90
                ....*....|....*...
gi 33301669 606 REPLASNDFLGGVRLGVG 623
Cdd:cd04026  89 WDRTTRNDFMGSLSFGVS 106

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: 84.32 E-value: 2.46e-19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKRSNPYVKTYLLPDKsrQGKRKTSIKRDTINPLYDETFR-YEISESL 438
Cdd:cd08388   3 GTLFFSLRYNSEKKALLVNIIECRDLPAMDEQSGTSDPYVKLQLLPEK--EHKVKTRVLRKTRNPVYDETFTfYGIPYNQ 80

                        90       100
                ....*....|....*....|....*
gi 33301669 439 LAQRTLQFSVWHHGRFGRNTFLGEA 463
Cdd:cd08388  81 LQDLSLHFAVLSFDRYSRDDVIGEV 105

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: 84.39 E-value: 2.62e-19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYIPASklpvggdrkkskggegGELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSP 578
Cdd:cd08405   2 GELLLSLCYNPTA----------------NRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNP 65

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33301669 579 HYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGvgtgisngevvdWMdSTGEEVSLWQKMRQYP 652
Cdd:cd08405  66 VFNESFIFN-IPLERLRETTLIITVMDKDRLSRNDLIGKIYLG------------WK-SGGLELKHWKDMLSKP 125

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: 82.50 E-value: 4.72e-19

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 375 LVIHVKECHQLAYADEAKKrSNPYVKTYLLPDKsrqgKRKTSIKRDTINPLYDETFRYEISESllAQRTLQFSVWHHGRF 454
Cdd:cd00030   1 LRVTVIEARNLPAKDLNGK-SDPYVKVSLGGKQ----KFKTKVVKNTLNPVWNETFEFPVLDP--ESDTLTVEVWDKDRF 73

                        90       100
                ....*....|....*....|....*....
gi 33301669 455 GRNTFLGEAEVHMDSWKLD-KKLDHCLPL 482
Cdd:cd00030  74 SKDDFLGEVEIPLSELLDSgKEGELWLPL 102

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: 82.38 E-value: 1.13e-18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAyADEAKKRSNPYVKTYLLPDKSRqgKRKTSIKRDTINPLYDETFRYE-ISESL 438
Cdd:cd08386   3 GRIQFSVSYDFQESTLTLKILKAVELP-AKDFSGTSDPFVKIYLLPDKKH--KLETKVKRKNLNPHWNETFLFEgFPYEK 79

                        90       100       110
                ....*....|....*....|....*....|....
gi 33301669 439 LAQRTLQFSVWHHGRFGRNTFLGEAEVHMDSWKL 472
Cdd:cd08386  80 LQQRVLYLQVLDYDRFSRNDPIGEVSLPLNKVDL 113

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: 81.94 E-value: 1.30e-18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYIPASKlpvggdrkkskggeggELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSP 578
Cdd:cd04035   2 GTLEFTLLYDPANS----------------ALHCTIIRAKGLKAMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNP 65

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 33301669 579 HYNHTFVYNGVRLEDLQHMCLELTVWDREPLaSNDFLGGVRL 620
Cdd:cd04035  66 EFNETLTYYGITEEDIQRKTLRLLVLDEDRF-GNDFLGETRI 106

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: 81.34 E-value: 1.42e-18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRnkasKRKTPVMKKTLSPHYNHTFVYNgvrLEDLQHMCLELTVWDREPL 609
Cdd:cd00030   1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQ----KFKTKVVKNTLNPVWNETFEFP---VLDPESDTLTVEVWDKDRF 73

                        90       100
                ....*....|....*....|....
gi 33301669 610 ASNDFLGGVRLGVGTGISNGEVVD 633
Cdd:cd00030  74 SKDDFLGEVEIPLSELLDSGKEGE 97

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: 80.99 E-value: 1.57e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669    374 TLVIHVKECHQLAYADEAKKrSNPYVKTYLLPDKSRqgKRKTSIKRDTINPLYDETFRYEISESLLaqRTLQFSVWHHGR 453
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGK-SDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPEL--AELEIEVYDKDR 75

                           90
                   ....*....|..
gi 33301669    454 FGRNTFLGEAEV 465
Cdd:smart00239  76 FGRDDFIGQVTI 87

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: 80.38 E-value: 4.96e-18

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYipasklpvggDRKKskggegGELQVWIKEAKNLTAAKSG-GTSDSFVKGYLLPMRNKASKRKTPVMKKTLS 577
Cdd:cd08521   1 GEIEFSLSY----------NYKT------GSLEVHIKECRNLAYADEKkKRSNPYVKVYLLPDKSKQSKRKTSVKKNTTN 64

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 33301669 578 PHYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRL 620
Cdd:cd08521  65 PVFNETLKYH-ISKSQLETRTLQLSVWHHDRFGRNTFLGEVEI 106

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: 9.41e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669    530 LQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKasKRKTPVMKKTLSPHYNHTFVYNgvrLEDLQHMCLELTVWDREPL 609
Cdd:smart00239   2 LTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFE---VPPPELAELEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*
gi 33301669    610 ASNDFLGGVRLGVGTGISNGEVVDW 634
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

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: 76.92 E-value: 9.30e-17

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 528 GELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKasKRKTPVMKKTLSPHYNHTFVYNgVRLEDLQHMCLELTVWDRE 607
Cdd:cd08385  16 NQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKK--KFETKVHRKTLNPVFNETFTFK-VPYSELGNKTLVFSVYDFD 92

                        90       100
                ....*....|....*....|....*....
gi 33301669 608 PLASNDFLGGVRLGVGTGISNGEVVDWMD 636
Cdd:cd08385  93 RFSKHDLIGEVRVPLLTVDLGHVTEEWRD 121

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: 76.47 E-value: 1.53e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAyADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd00276   1 GELLLSLSYLPTAERLTVVVLKARNLP-PSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQL 79

                        90       100
                ....*....|....*....|....*.
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLGEAEV 465
Cdd:cd00276  80 EEVSLVITVVDKDSVGRNEVIGQVVL 105

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: 75.38 E-value: 3.32e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 366 LKFEQKTQTLVIHVKECHQLAYADeAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLLAQRtLQ 445
Cdd:cd04026   6 LKISVKDNKLTVEVREAKNLIPMD-PNGLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKDRR-LS 83

                        90
                ....*....|....*.
gi 33301669 446 FSVWHHGRFGRNTFLG 461
Cdd:cd04026  84 IEVWDWDRTTRNDFMG 99

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: 75.13 E-value: 4.47e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADeAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd08402   2 GDICFSLRYVPTAGKLTVVILEAKNLKKMD-VGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQI 80

                        90       100
                ....*....|....*....|...
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLGE 462
Cdd:cd08402  81 QKVHLIVTVLDYDRIGKNDPIGK 103

FYVE-related domain found in the synaptotagmin-like proteins 3, 4, 5; The synaptotagmin-like proteins 1-5 (Slp1-5) family belongs to the carboxyl-terminal-type (C-type) tandem C2 proteins superfamily, which also contains the synaptotagmin and the Doc2 families. Slp proteins are putative membrane trafficking proteins that are characterized by the presence of a unique N-terminal Slp homology domain (SHD), and C-terminal tandem C2 domains (known as the C2A domain and C2B domain). The SHD consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2. The SHD1 and SHD2 of Slp3, Slp4 and Slp5 are separated by a putative FYVE zinc finger. By contrast, Slp1 and Slp2 lack such zinc finger and their SHD1 and SHD2 are linked together. This model corresponds to the FYVE zinc finger. At this point, Slp1 and Slp2 are not included in this model. Moreover, the FYVE domains of Slp3, Slp4 and Slp5 resemble a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.

Pssm-ID: 277286 Cd Length: 48 Bit Score: 71.95 E-value: 7.26e-16

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 33301669  61 RTCARCQEGLGRLIPKSSTCVGCNHLVCRECRVLESN-GSWRCKVCSK 107
Cdd:cd15747   1 RICARCREKLGFIFNRGARCPKCSHKVCKKCRVLTSNtGKWLCTVCHK 48

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: 74.24 E-value: 8.49e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAyADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYE-ISESL 438
Cdd:cd04035   2 GTLEFTLLYDPANSALHCTIIRAKGLK-AMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYgITEED 80

                        90       100
                ....*....|....*....|....*..
gi 33301669 439 LAQRTLQFSVWHHGRFGrNTFLGEAEV 465
Cdd:cd04035  81 IQRKTLRLLVLDEDRFG-NDFLGETRI 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: 73.85 E-value: 1.03e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSPHYNHTFVYNgVRLEDLQHMCLELTVWDREPL 609
Cdd:cd04030  18 LIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFP-VSLEELKRRTLDVAVKNSKSF 96

                        90
                ....*....|...
gi 33301669 610 AS--NDFLGGVRL 620
Cdd:cd04030  97 LSreKKLLGQVLI 109

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: 73.13 E-value: 2.01e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAAKSGGTSDSFVKGYLLPmrNKASKRKTPVMKKTLSPHYNHTFVYNGVRLEDLQHMCLELTVWDREPL 609
Cdd:cd08386  18 LTLKILKAVELPAKDFSGTSDPFVKIYLLP--DKKHKLETKVKRKNLNPHWNETFLFEGFPYEKLQQRVLYLQVLDYDRF 95

                        90
                ....*....|.
gi 33301669 610 ASNDFLGGVRL 620
Cdd:cd08386  96 SRNDPIGEVSL 106

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: 72.05 E-value: 4.34e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 358 VTGKIAFSLKFEQKTQTLVIHVKECHQLAyADEAKKRSNPYVKTYLLPDKSRQgkRKTSIKRDTINPLYDETFRYEISES 437
Cdd:cd08387   1 TRGELHFSLEYDKDMGILNVKLIQARNLQ-PRDFSGTADPYCKVRLLPDRSNT--KQSKIHKKTLNPEFDESFVFEVPPQ 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 33301669 438 LLAQRTLQFSVWHHGRFGRNTFLGEAEVHMDSWKLDKKLD 477
Cdd:cd08387  78 ELPKRTLEVLLYDFDQFSRDECIGVVELPLAEVDLSEKLD 117

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: 72.27 E-value: 4.51e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 529 ELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMR--NKASKRKTPVMKKTLSPHYNHTFVYNgVRLEDLQH--MCLELTVW 604
Cdd:cd04009  17 SLRVEILNARNLLPLDSNGSSDPFVKVELLPRHlfPDVPTPKTQVKKKTLFPLFDESFEFN-VPPEQCSVegALLLFTVK 95

                        90
                ....*....|..
gi 33301669 605 DREPLASNDFLG 616
Cdd:cd04009  96 DYDLLGSNDFEG 107

FYVE-related domain found in synaptotagmin-like protein 3 (Slp3) and similar proteins; Slp3, also termed exophilin-6, functions as a Rab27A-specific effector in cytotoxic T lymphocytes. It binds to kinesin-1 motor through interaction with the tetratricopeptide repeat of the kinesin-1 light chain (KLC1). The kinesin-1/Slp3/Rab27a complex plays a role in mediating the terminal transport of lytic granules to the immune synapse. Slp3 contains an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains. The Slp homology domain (SHD) consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp3 are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. In addition, the Slp3 C2A domain showed Ca2+-dependent phospholipid binding activity. At this point, Slp3 is a Ca2+-dependent isoform in Slp proteins family.

Pssm-ID: 277304 Cd Length: 48 Bit Score: 67.91 E-value: 1.71e-14

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 33301669  60 DRTCARCQEGLGRLIPKSSTCVGCNHLVCRECRVLESNGSWRCKVC 105
Cdd:cd15765   1 ERSCARCQKPLGKLLNRGAVCNGCSHRVCSECRVFLGREIWKCTVC 46

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: 70.15 E-value: 2.82e-14

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 498 KGELVVSLKYIPASklpvggdrkkskggegGELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLS 577
Cdd:cd08404   1 RGELLLSLCYQPTT----------------NRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRISKKKTHVKKCTLN 64

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 33301669 578 PHYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGVGTGISNGEVV-DWMDSTGEEVSLWQKMR 649
Cdd:cd08404  65 PVFNESFVFD-IPSEELEDISVEFLVLDSDRVTKNEVIGRLVLGPKASGSGGHHWkEVCNPPRRQIAEWHMLC 136

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: 66.84 E-value: 3.74e-13

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYIPASklpvggdrkkskggegGELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSP 578
Cdd:cd08410   1 GELLLSLNYLPSA----------------GRLNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDP 64

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33301669 579 HYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVrlgvgtgisngeVVDWMDSTGEEVSLWQKMR 649
Cdd:cd08410  65 FYNESFSFK-VPQEELENVSLVFTVYGHNVKSSNDFIGRI------------VIGQYSSGPSETNHWRRML 122

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: 65.61 E-value: 1.15e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYIPASklpvggdrkkskggegGELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSP 578
Cdd:cd08403   1 GELMFSLCYLPTA----------------GRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNP 64

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 33301669 579 HYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGV 622
Cdd:cd08403  65 TYNEALVFD-VPPENVDNVSLIIAVVDYDRVGHNELIGVCRVGP 107

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: 65.34 E-value: 1.40e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKrSNPYVKTYLLPDK--SRQGKRKTSIKRDTINPLYDETFRYEIS-- 435
Cdd:cd04009   3 GVLTVKAYYRASEQSLRVEILNARNLLPLDSNGS-SDPFVKVELLPRHlfPDVPTPKTQVKKKTLFPLFDESFEFNVPpe 81

                        90       100       110
                ....*....|....*....|....*....|....
gi 33301669 436 ESLLAQRTLQFSVWHHGRFGRNTFLGEAEVHMDS 469
Cdd:cd04009  82 QCSVEGALLLFTVKDYDLLGSNDFEGEAFLPLND 115

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: 65.13 E-value: 1.82e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKrSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd08405   2 GELLLSLCYNPTANRITVNIIKARNLKAMDINGT-SDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFNIPLERL 80

                        90       100
                ....*....|....*....|....
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLGEA 463
Cdd:cd08405  81 RETTLIITVMDKDRLSRNDLIGKI 104

FYVE-related domain found in synaptotagmin-like protein 5 (Slp5) and similar proteins; Slp5 is a novel Rab27A-specific effector that is highly expressed in placenta and liver. Slp5 specifically interacted with the GTP-bound form of Rab27A and is involved in Rab27A-dependent membrane trafficking in specific tissues. Slp5 contains an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains. The Slp homology domain (SHD) consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp5 are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.

Pssm-ID: 277305 Cd Length: 47 Bit Score: 61.76 E-value: 2.13e-12

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 33301669  61 RTCARCQEGLGRLIPKSSTCVGCNHLVCRECRVLESNGSWRCKVCSK 107
Cdd:cd15766   1 RLCVRCLKNLGLIFDRGDLCQECQLRVCSECRVLGANGKWKCTVCAK 47

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: 63.60 E-value: 5.54e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKrSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd08404   2 GELLLSLCYQPTTNRLTVVVLKARHLPKMDVSGL-ADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFDIPSEEL 80

                        90       100       110
                ....*....|....*....|....*....|
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLGEAEVHMDS 469
Cdd:cd08404  81 EDISVEFLVLDSDRVTKNEVIGRLVLGPKA 110

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: 63.30 E-value: 7.01e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKrSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd08403   1 GELMFSLCYLPTAGRLTLTIIKARNLKAMDITGF-SDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENV 79

                        90       100
                ....*....|....*....|....*.
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLGEAEV 465
Cdd:cd08403  80 DNVSLIIAVVDYDRVGHNELIGVCRV 105

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; 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. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. 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: 175995 [Multi-domain] Cd Length: 125 Bit Score: 62.07 E-value: 1.65e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYipasklpvggDRKKskggegGELQVWIKEAKNL-TAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLS 577
Cdd:cd04029   2 GEILFSLSY----------DYKT------QSLNVHVKECRNLaYGDEAKKRSNPYVKTYLLPDKSRQSKRKTSIKRNTTN 65

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 33301669 578 PHYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRL 620
Cdd:cd04029  66 PVYNETLKYS-ISHSQLETRTLQLSVWHYDRFGRNTFLGEVEI 107

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. 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: 176060 [Multi-domain] Cd Length: 126 Bit Score: 60.46 E-value: 5.25e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 389 DEAKKRSNPYVKTYLlpDKSRQgKRKTSIKRDTINPLYDETFRYEISESllaQRTLQFSVWHHGRFGRNTFLGEAEVHMD 468
Cdd:cd08678  12 SEAAGSSNPYCVLEM--DEPPQ-KYQSSTQKNTSNPFWDEHFLFELSPN---SKELLFEVYDNGKKSDSKFLGLAIVPFD 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 33301669 469 SWKLDKKLDHCLPLHGKIStESSPGlpahKGELVVSLKYIPASKLP 514
Cdd:cd08678  86 ELRKNPSGRQIFPLQGRPY-EGDSV----SGSITVEFLFMEPAELP 126

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. 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: 176051 [Multi-domain] Cd Length: 136 Bit Score: 59.42 E-value: 1.43e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLaYADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd08406   2 GEILLSLSYLPTAERLTVVVVKARNL-VWDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFSVPAIVL 80

                        90       100
                ....*....|....*....|..
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLG 461
Cdd:cd08406  81 QDLSLRVTVAESTEDGKTPNVG 102

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: 58.85 E-value: 1.44e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 528 GELQVWIKEAKNLTAAKSGGTSDSFVkgyLLPMRNkaSKRKTPVMKKTLSPHYNHTFVYNgvrLEDLqHMCLELTVWDRE 607
Cdd:cd08377   1 GFLQVKVIRASGLAAADIGGKSDPFC---VLELVN--ARLQTHTIYKTLNPEWNKIFTFP---IKDI-HDVLEVTVYDED 71

                        90       100
                ....*....|....*....|...
gi 33301669 608 PLASNDFLGGVRLGVGTgISNGE 630
Cdd:cd08377  72 KDKKPEFLGKVAIPLLS-IKNGE 93

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: 58.92 E-value: 2.53e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 375 LVIHVKECHQLAyadeaKKR---SNPYVK-TYLLPDKSRQgkRKTSIKRDTINPLYDETFRYE-------------ISES 437
Cdd:cd08675   1 LSVRVLECRDLA-----LKSngtCDPFARvTLNYSSKTDT--KRTKVKKKTNNPRFDEAFYFEltigfsyekksfkVEEE 73

                        90       100
                ....*....|....*....|....*...
gi 33301669 438 LLAQRTLQFSVWHHGRFGRNTFLGEAEV 465
Cdd:cd08675  74 DLEKSELRVELWHASMVSGDDFLGEVRI 101

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: 58.13 E-value: 3.72e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAAK-SGGTSDSFVKGYLLPmrNKASKRKTPVMKKTLSPHYNHTFVYNGVRLEDLQHMCLELTV--WDR 606
Cdd:cd08388  18 LLVNIIECRDLPAMDeQSGTSDPYVKLQLLP--EKEHKVKTRVLRKTRNPVYDETFTFYGIPYNQLQDLSLHFAVlsFDR 95

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. 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: 176051 [Multi-domain] Cd Length: 136 Bit Score: 57.88 E-value: 5.11e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYIPASKlpvggdrkkskggeggELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSP 578
Cdd:cd08406   2 GEILLSLSYLPTAE----------------RLTVVVVKARNLVWDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNP 65

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 33301669 579 HYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRLG---VGTGISNgevvdW---MDSTGEEVSLWQKMR 649
Cdd:cd08406  66 IFNEAMIFS-VPAIVLQDLSLRVTVAESTEDGKTPNVGHVIIGpaaSGMGLSH-----WnqmLASLRKPVAMWHPLR 136

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: 57.77 E-value: 5.17e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLtAAKSGGTSDSFVK-GYLLPMRNKAskRKTPVMKKTLSPHYNHTFVYNG------------VRLEDLQH 596
Cdd:cd08675   1 LSVRVLECRDL-ALKSNGTCDPFARvTLNYSSKTDT--KRTKVKKKTNNPRFDEAFYFELtigfsyekksfkVEEEDLEK 77

                        90       100
                ....*....|....*....|....
gi 33301669 597 MCLELTVWDREPLASNDFLGGVRL 620
Cdd:cd08675  78 SELRVELWHASMVSGDDFLGEVRI 101

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: 57.59 E-value: 7.27e-10

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKrSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLL 439
Cdd:cd08410   1 GELLLSLNYLPSAGRLNVDIIRAKQLLQTDMSQG-SDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFKVPQEEL 79

                        90       100
                ....*....|....*....|...
gi 33301669 440 AQRTLQFSVWHHGRFGRNTFLGE 462
Cdd:cd08410  80 ENVSLVFTVYGHNVKSSNDFIGR 102

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: 54.72 E-value: 5.46e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 525 GEGGELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKAskRKTPVMKKTLSPHYNHTFVYnGVRLEDLQHMCLELTVW 604
Cdd:cd08387  13 KDMGILNVKLIQARNLQPRDFSGTADPYCKVRLLPDRSNT--KQSKIHKKTLNPEFDESFVF-EVPPQELPKRTLEVLLY 89

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 33301669 605 DREPLASNDFLGGVRLGVGTgisngevVDWMdstgEEVSLWQKMR 649
Cdd:cd08387  90 DFDQFSRDECIGVVELPLAE-------VDLS----EKLDLWRKIQ 123

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the 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: 176067 [Multi-domain] Cd Length: 119 Bit Score: 54.38 E-value: 5.75e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 366 LKFEQKTQTLVIHVKECHQLAyadEAKKRS-NPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESLLAQRTL 444
Cdd:cd08685   5 LSIEGQNRKLTLHVLEAKGLR---STNSGTcNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRLL 81

                        90
                ....*....|....*.
gi 33301669 445 qFSVWHHGRFGRNTFL 460
Cdd:cd08685  82 -VTVWNKLSKSRDSGL 96

C2 domain second 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: 175994 [Multi-domain] Cd Length: 146 Bit Score: 53.93 E-value: 1.53e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 357 SVTGKIafSLKFEQKTQTLVIHVKECHQLAYADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISE 436
Cdd:cd04028  15 PSMGDI--QLGLYDKKGQLEVEVIRARGLVQKPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDVSP 92

                        90       100       110
                ....*....|....*....|....*....|...
gi 33301669 437 SllaQRTLQFSVW-HHGRFGRNTFLGEAEVHMD 468
Cdd:cd04028  93 T---GKTLQVIVWgDYGRMDKKVFMGVAQILLD 122

C2 domain second repeat present in Synaptotagmin 15; 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. 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: 176054 [Multi-domain] Cd Length: 137 Bit Score: 53.11 E-value: 2.57e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYIPASklpvggdrkkskggegGELQVWIKEAKNLTAAKSGGTsDSFVKGYLLPMRNKASKRKTPVMKKTLSP 578
Cdd:cd08409   2 GDIQISLTYNPTL----------------NRLTVVVLRARGLRQLDHAHT-SVYVKVSLMIHNKVVKTKKTEVVDGAASP 64

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33301669 579 HYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGvgtgisngevvDWMDSTGEEVSLWQKMRQYP 652
Cdd:cd08409  65 SFNESFSFK-VTSRQLDTASLSLSVMQSGGVRKSKLLGRVVLG-----------PFMYARGKELEHWNDMLSKP 126

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: 53.17 E-value: 2.66e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 375 LVIHVKECHQLAYADEAkkrSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETF-------------RYEISESLLAQ 441
Cdd:cd04010   2 LSVRVIECSDLALKNGT---CDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFyfdvtidsspekkQFEMPEEDAEK 78

                        90       100
                ....*....|....*....|.
gi 33301669 442 RTLQFSVWHHGRFGRNTFLGE 462
Cdd:cd04010  79 LELRVDLWHASMGGGDVFLGE 99

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: 51.81 E-value: 3.86e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 377 IHVKECHQLAYADeakkrSNPYVKTYLLPDKsrqgkRKTSIKRDTINPLYDETFRYEISESL--LAQRTLQFSVWHHGRF 454
Cdd:cd04011   8 VRVIEARQLVGGN-----IDPVVKVEVGGQK-----KYTSVKKGTNCPFYNEYFFFNFHESPdeLFDKIIKISVYDSRSL 77

                        90
                ....*....|.
gi 33301669 455 GRNTFLGEAEV 465
Cdd:cd04011  78 RSDTLIGSFKL 88

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: 51.57 E-value: 6.63e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAAKSGGTSDSFVKgyllpMRNKASKRKTPVMKKTLSPHYNHTFVYNGVRLEDLQHMCLELTVW-DREP 608
Cdd:cd04022   2 LVVEVVDAQDLMPKDGQGSSSAYVE-----LDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDPSRLSNLVLEVYVYnDRRS 76

                        90       100
                ....*....|....*....|....
gi 33301669 609 LASNDFLGGVRLGVGTGISNGEVV 632
Cdd:cd04022  77 GRRRSFLGRVRISGTSFVPPSEAV 100

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. 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: 176062 Cd Length: 124 Bit Score: 51.08 E-value: 1.04e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 361 KIAFSLKFEQKTQTLVIHV---KECHQLAYADEAKKrsnpYVKTYLLP---DKSRQGKRKTSIkrDTINPLYDETFRYEI 434
Cdd:cd08680   2 QVQIGLRYDSGDSSLVISVeqlRNLSALSIPENSKV----YVRVALLPcssSTSCLFRTKALE--DQDKPVFNEVFRVPI 75

                        90       100       110
                ....*....|....*....|....*....|.
gi 33301669 435 SESLLAQRTLQFSVWHHGRFGRNTFLGEAEV 465
Cdd:cd08680  76 SSTKLYQKTLQVDVCSVGPDQQEECLGGAQI 106

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: 50.00 E-value: 1.81e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAA-KSGGTSDSFVKgyllpMRNKASKRKTPVMKKTLSPHYN-HTFVYNgVRLEDLQHMCLELTVWDRE 607
Cdd:cd08688   1 LKVRVVAARDLPVMdRSSDLTDAFVE-----VKFGSTTYKTDVVKKSLNPVWNsEWFRFE-VDDEELQDEPLQIRVMDHD 74

                        90
                ....*....|.
gi 33301669 608 PLASNDFLGGV 618
Cdd:cd08688  75 TYSANDAIGKV 85

FYVE-related domain found in rabphilin-3A and similar proteins; Rabphilin-3A, also termed exophilin-1, is an effector protein that binds to the GTP-bound form of Rab3A, which is one of the most abundant Rab proteins in neurons and predominantly localized to synaptic vesicles. Rabphilin-3A is homologous to alpha-Rab3-interacting molecules (RIMs). It is a multi-domain protein containing an N-terminal Rab3A effector domain, a proline-rich linker region, and two tandem C2 domains. The effector domain binds specifically to the activated GTP-bound state of Rab3A and harbors a conserved FYVE zinc finger. The C2 domains are responsible for the binding of phosphatidylinositol-4,5-bisphosphate (PIP2) , a key player in the neurotransmitter release process. Thus, Rabphilin-3A has also been implicated in vesicle trafficking. The FYVE domain of Rabphilin-3A resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.

Pssm-ID: 277301 Cd Length: 80 Bit Score: 48.80 E-value: 2.19e-07

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33301669  63 CARCQEGLGRLIPKSSTCVGCNHLVCRECRVLESNGS---WRCKVCSKEIELKKATGDWFY 120
Cdd:cd15762   7 CILCGEQLGGAGSACVVCEDCKKNVCTKCGVQTNNRPhsvWLCKICSEQREVWKRSGAWFF 67

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: 50.47 E-value: 2.39e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAakSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSPHYNHTFVYNGVR------------LEDLQHM 597
Cdd:cd04010   2 LSVRVIECSDLAL--KNGTCDPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVTIdsspekkqfempEEDAEKL 79

                        90       100
                ....*....|....*....|...
gi 33301669 598 CLELTVWDREPLASNDFLGGVRL 620
Cdd:cd04010  80 ELRVDLWHASMGGGDVFLGEVRI 102

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: 49.79 E-value: 2.55e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 536 EAKNLTAAKSGGTSDSFVKgyllpMRNKASKRKTPVMKKTLSPHYNHTFVYngvRLEDLQHMCLELTVWDREPLASNDFL 615
Cdd:cd04025   8 EARDLAPKDRNGTSDPFVR-----VFYNGQTLETSVVKKSCYPRWNEVFEF---ELMEGADSPLSVEVWDWDLVSKNDFL 79

                        90
                ....*....|....*....
gi 33301669 616 GGVRLGVGTGISNGEVVDW 634
Cdd:cd04025  80 GKVVFSIQTLQQAKQEEGW 98

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: 49.95 E-value: 2.83e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 388 ADEAKKRSNPYVktyLLPDKSRQgKR--KTSIKRDTINPLYDETFryEISESLLAQRTLQFSVWHHGRFGRNTFLGEAEV 465
Cdd:cd04043  15 ADSSNGLSDPYV---TLVDTNGK-RRiaKTRTIYDTLNPRWDEEF--ELEVPAGEPLWISATVWDRSFVGKHDLCGRASL 88


                ....
gi 33301669 466 HMDS 469
Cdd:cd04043  89 KLDP 92

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

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 49.20 E-value: 3.55e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 374 TLVIHVKECHQLAYADEAKKrSNPYVKTYLlpdKSRQGKRKTSIKRDtINPLYDETFRYEIsESLLAqrTLQFSVWHHGR 453
Cdd:cd04042   1 QLDIHLKEGRNLAARDRGGT-SDPYVKFKY---GGKTVYKSKTIYKN-LNPVWDEKFTLPI-EDVTQ--PLYIKVFDYDR 72

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 33301669 454 FGRNTFLGEAEVHMDSWKLDKKLDHCLPLhgkisTESSPGLPAHKGELVVSL 505
Cdd:cd04042  73 GLTDDFMGSAFVDLSTLELNKPTEVKLKL-----EDPNSDEDLGYISLVVTL 119

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: 49.16 E-value: 3.97e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 360 GKIAFSLKFEQKTQTLVIHVKECHQLAyadeAKKRSNP---YVKTYLLPDKsRQgKRKTSIKRDTiNPLYDETFRY-EIS 435
Cdd:cd08389   3 GDLDVAFEYDPSARKLTVTVIRAQDIP----TKDRGGAsswQVHLVLLPSK-KQ-RAKTKVQRGP-NPVFNETFTFsRVE 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 33301669 436 ESLLAQRTLQFSVWHHGRFGRNTFLGEAEVHMDSWKLDKKLDHCLPL 482
Cdd:cd08389  76 PEELNNMALRFRLYGVERMRKERLIGEKVVPLSQLNLEGETTVWLTL 122

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: 49.67 E-value: 3.99e-07

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33301669 393 KRSNPYVKTYLLpDKSRQ--GKRKTSIKRDTINPLYDETFRYEISESLLAQRTLQFSVWHHGRFGRNTFLG 461
Cdd:cd08408  34 KAPDTYVKLTLL-NSDGQeiSKSKTSIRRGQPDPEFKETFVFQVALFQLSEVTLMFSVYNKRKMKRKEMIG 103

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: 49.34 E-value: 4.45e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 528 GELQVWIKEAKNLTAA--KSGGTSDSFVKGYLlpmrnKASKRKTPVMKKTLSPHYNhtfVYNGVRLEDLQHMCLELTVWD 605
Cdd:cd04024   1 GVLRVHVVEAKDLAAKdrSGKGKSDPYAILSV-----GAQRFKTQTIPNTLNPKWN---YWCEFPIFSAQNQLLKLILWD 72

                        90       100
                ....*....|....*....|....*.
gi 33301669 606 REPLASNDFLGGVRLGVGTGISNGEV 631
Cdd:cd04024  73 KDRFAGKDYLGEFDIALEEVFADGKT 98

C2 domain first repeat present in Synaptotagmin-like protein 3; 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. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes 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 first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176038 [Multi-domain] Cd Length: 128 Bit Score: 48.29 E-value: 9.18e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAAKSGGTS-DSFVKGYLLPMRNKASKRKTPVMKKTLSPHYNHTFVYNgVRLEDLQHMCLELTVWDREP 608
Cdd:cd08392  17 LEITIKACRNLAYGDEKKKKcHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYV-VEADLLSSRQLQVSVWHSRT 95

                        90
                ....*....|
gi 33301669 609 LASNDFLGGV 618
Cdd:cd08392  96 LKRRVFLGEV 105

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: 47.64 E-value: 1.27e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTA-AKSGGTSDSFVKGYLLP--MRNKASKrktpVMKKTLSPHYNHTFVYNgVRLEDLQHMCLELTVWDR 606
Cdd:cd08390  16 LTVSLIKARNLPPrTKDVAHCDPFVKVCLLPdeRRSLQSK----VKRKTQNPNFDETFVFQ-VSFKELQRRTLRLSVYDV 90

                        90       100       110
                ....*....|....*....|....*....|
gi 33301669 607 EPLASNDFLGGVRLGVGTGISNGEVVDWMD 636
Cdd:cd08390  91 DRFSRHCIIGHVLFPLKDLDLVKGGVVWRD 120

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: 47.92 E-value: 1.31e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 372 TQTLVIHVKECHQLAYADEAKKRS-NPYVKTYL--LPDKSRQgKRKTSIKRD-TINPLYDETFRYEISESLLAqrTLQFS 447
Cdd:cd00275   1 PLTLTIKIISGQQLPKPKGDKGSIvDPYVEVEIhgLPADDSA-KFKTKVVKNnGFNPVWNETFEFDVTVPELA--FLRFV 77

                        90       100
                ....*....|....*....|..
gi 33301669 448 VWHHGRFGrNTFLGEAEVHMDS 469
Cdd:cd00275  78 VYDEDSGD-DDFLGQACLPLDS 98

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: 47.38 E-value: 2.19e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 519 RKKSKGGegGELQVWIKEAKNLTAAKSGGTSDSFVKgyllpmRNKASKR-KTPVMKKTLSPHYNHT---FVYngvrleDL 594
Cdd:cd08375   8 SQRASGI--GRLMVVIVEGRDLKPCNSNGKSDPYCE------VSMGSQEhKTKVVSDTLNPKWNSSmqfFVK------DL 73

                        90       100
                ....*....|....*....|..
gi 33301669 595 QHMCLELTVWDREPLASNDFLG 616
Cdd:cd08375  74 EQDVLCITVFDRDFFSPDDFLG 95

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: 46.52 E-value: 4.07e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 528 GELQVWIKEAKNLTAAK------SGGTSDSFVKgyllpMRNKASKRKTPVMKKTLSPHYNHTFvynGVRLEDLQHMCLEL 601
Cdd:cd08391   1 GVLRIHVIEAQDLVAKDkfvgglVKGKSDPYVI-----VRVGAQTFKSKVIKENLNPKWNEVY---EAVVDEVPGQELEI 72

                        90       100       110
                ....*....|....*....|....*....|....
gi 33301669 602 TVWDREPlASNDFLGGVRLGVGTGISNGEVVDWM 635
Cdd:cd08391  73 ELFDEDP-DKDDFLGRLSIDLGSVEKKGFIDEWL 105

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: 46.15 E-value: 5.36e-06

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 33301669 566 KRKTPVMKKTLSPHYNHTFVYNGVRLedlQHMCLELTVWDREPlASNDFLGGVRLGVG 623
Cdd:cd08378  29 KGSTKAIERTSNPEWNQVFAFSKDRL---QGSTLEVSVWDKDK-AKDDFLGGVCFDLS 82

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: 45.26 E-value: 7.67e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 531 QVWIKEAKNLtaakSGGTSDSFVKGYLLpmrnkASKRKTPVMKKTLSPHYNHTFVYN-GVRLEDLQHMCLELTVWDREPL 609
Cdd:cd04011   7 RVRVIEARQL----VGGNIDPVVKVEVG-----GQKKYTSVKKGTNCPFYNEYFFFNfHESPDELFDKIIKISVYDSRSL 77

                        90
                ....*....|....*
gi 33301669 610 ASNDFLGGVRLGVGT 624
Cdd:cd04011  78 RSDTLIGSFKLDVGT 92

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: 45.32 E-value: 8.11e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 536 EAKNLTAAKSGGTSDSFVKgylLPMRNKasKRKTPVMKKTLSPHYNHTFVYNgvrLEDLQHMCLELTVWDREPLASNDFL 615
Cdd:cd08376   8 EGKNLPPMDDNGLSDPYVK---FRLGNE--KYKSKVCSKTLNPQWLEQFDLH---LFDDQSQILEIEVWDKDTGKKDEFI 79


                .
gi 33301669 616 G 616
Cdd:cd08376  80 G 80

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: 46.21 E-value: 8.46e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAAKSGGTSDSFVKGYLLPMRNKASKRK------------------------TPVMKKTLSPHYNHTFV 585
Cdd:cd08676  30 LKVTVIEAKGLLAKDVNGFSDPYCMLGIVPASRERNSEKskkrkshrkkavlkdtvpaksikvTEVKPQTLNPVWNETFR 109

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 33301669 586 YNgvrLEDLQHMCLELTVWDREplasNDFLGGVRLGVGTGISNGE 630
Cdd:cd08676 110 FE---VEDVSNDQLHLDIWDHD----DDFLGCVNIPLKDLPSCGL 147

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: 44.87 E-value: 1.11e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAAKSGGTSDSFVKGYLlpmrNKASKRKTPVMKKTLSPHYNHTF-------VYNGVRLEdlqhmclelt 602
Cdd:cd04040   1 LTVDVISAENLPSADRNGKSDPFVKFYL----NGEKVFKTKTIKKTLNPVWNESFevpvpsrVRAVLKVE---------- 66

                        90
                ....*....|....
gi 33301669 603 VWDREPLASNDFLG 616
Cdd:cd04040  67 VYDWDRGGKDDLLG 80

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: 45.02 E-value: 1.21e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 375 LVIHVKECHQLAYADEAKKrSNPYVKTYLLPDKSRqgkrkTSIKRDTINPLYDETFRYEISE-SLLAQRTLQFSVWHHGR 453
Cdd:cd04022   2 LVVEVVDAQDLMPKDGQGS-SSAYVELDFDGQKKR-----TRTKPKDLNPVWNEKLVFNVSDpSRLSNLVLEVYVYNDRR 75


                ....*....
gi 33301669 454 FGR-NTFLG 461
Cdd:cd04022  76 SGRrRSFLG 84

C2 domain second repeat present in Synaptotagmin 15; 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. 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: 176054 [Multi-domain] Cd Length: 137 Bit Score: 45.40 E-value: 1.38e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 359 TGKIAFSLKFEQKTQTLVIHVKECHQLAYADEAKKrsNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETFRYEISESL 438
Cdd:cd08409   1 LGDIQISLTYNPTLNRLTVVVLRARGLRQLDHAHT--SVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSFKVTSRQ 78

                        90       100
                ....*....|....*....|...
gi 33301669 439 LAQRTLQFSVWHHGRFGRNTFLG 461
Cdd:cd08409  79 LDTASLSLSVMQSGGVRKSKLLG 101

FYVE-related domain found in Slp homolog lacking C2 domains a (SlaC2-a) and similar proteins; SlaC2-a, also termed melanophilin, or exophilin-3, is a GTP-bound form of Rab27A-, myosin Va-, and actin-binding protein present on melanosomes. It is involved in the control of transferring of melanosomes from microtubules to actin filaments. It also functions as a melanocyte type myosin Va (McM5) binding partner and directly activates the actin-activated ATPase activity of McM5 through forming a tripartite protein complex with Rab27A and an actin-based motor myosin Va. SlaC2-a belongs to the Slp homolog lacking C2 domains (Slac2) family. It contains an N-terminal Slp homology domain (SHD), but lacks tandem C2 domains. The SHD consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of SlaC2-a are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. Moreover, Slac2-a has a middle myosin-binding domain and a C-terminal actin-binding domain.

Pssm-ID: 277291 Cd Length: 76 Bit Score: 43.25 E-value: 1.79e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33301669  63 CARCQEGLGRLIPKSSTCVGCNHLVCREC-RVLESNGSWRCKVCSKEIELKKATGDWFYDQKVNRFDyRTGS 133
Cdd:cd15752   3 CARCLQPFQFLLNSGRQCLDCGLRTCKSCsRYHPEEQGWVCDPCHLARVVKIGSLEWYYNHVRARFK-RFGS 73

FYVE-related domain found in rabphilin-3A, Rab effector Noc2, and similar proteins; This family includes rabphilin-3A and Rab effector Noc2. Rabphilin-3A, also termed exophilin-1, is an effector protein that binds to the GTP-bound form of Rab3A, which is one of the most abundant Rab proteins in neurons and predominantly localized to synaptic vesicles. Rabphilin-3A is homologous to alpha-Rab3-interacting molecules (RIMs). It is a multi-domain protein containing an N-terminal Rab3A effector domain, a proline-rich linker region, and two tandem C2 domains. The effector domain binds specifically to the activated GTP-bound state of Rab3A and harbors a conserved FYVE zinc finger. The C2 domains are responsible for the binding of phosphatidylinositol-4,5-bisphosphate (PIP2) , a key player in the neurotransmitter release process. Thus, Rabphilin-3A has also been implicated in vesicle trafficking. Rab effector Noc2, also termed No C2 domains protein, or rabphilin-3A-like protein (RPH3AL), is a Rab3 effector that mediates the regulation of secretory vesicle exocytosis in neurons and certain endocrine cells. It also functions as a Rab27 effector and is involved in isoproterenol (IPR)-stimulated amylase release from acinar cells. Noc2 contains an N-terminal Rab3A effector domain which only harbors a conserved FYVE zinc finger. The FYVE domains of Rabphilin-3A and Noc2 resemble a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.

Pssm-ID: 277285 Cd Length: 55 Bit Score: 41.86 E-value: 3.42e-05

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 33301669  62 TCARCQEGLGRLIPKSSTCVGCNHLVCRECRVLESNGS----WRCKVCS 106
Cdd:cd15746   6 QCILCGDEFGLLGASPVLCKDCRKAVCTKCGVETTNSNkqpiWLCKICS 54

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the 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: 176067 [Multi-domain] Cd Length: 119 Bit Score: 43.21 E-value: 4.79e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 517 GDRKKSKGGEGGELQVWIKEAKNLTAAKSGgTSDSFVKGYLLPMRNKASKRKTPVMKKTLSPHYNHTFVYNgVRLEDLQH 596
Cdd:cd08685   1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSG-TCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFD-VNERDYQK 78

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 33301669 597 MCLeLTVWDREPLASND-FLGGVRLGVGTGISNGEVVDW 634
Cdd:cd08685  79 RLL-VTVWNKLSKSRDSgLLGCMSFGVKSIVNQKEISGW 116

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: 43.51 E-value: 5.02e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 538 KNLTAAKSggtSDSFVKGYLL-PMRNKASKRKTPVMKKTLSPHYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLG 616
Cdd:cd08408  28 KNLAMNKA---PDTYVKLTLLnSDGQEISKSKTSIRRGQPDPEFKETFVFQ-VALFQLSEVTLMFSVYNKRKMKRKEMIG 103

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 33301669 617 GVRLGVGTgisngevvdwmdSTGEEVSLWQKMRQYPG 653
Cdd:cd08408 104 WFSLGLNS------------SGEEEEEHWNEMKESKG 128

FYVE-related domain found in Slp homolog lacking C2 domains c (SlaC2-c) and similar proteins; SlaC2-c, also termed Rab effector MyRIP, or exophilin-8, or myosin-VIIa- and Rab-interacting protein, or synaptotagmin-like protein lacking C2 domains c, is a GTP-bound form of Rab27A-, myosin Va/VIIa-, and actin-binding protein mainly present on retinal melanosomes and secretory granules. It may play a role in insulin granule exocytosis. It is also involved in the control of isoproterenol (IPR)-induced amylase release from parotid acinar cells. SlaC2-c belongs to the Slp homolog lacking C2 domains (Slac2) family. It contains an N-terminal Slp homology domain (SHD), but lacks tandem C2 domains. The SHD consists of two conserved regions, designated SHD1 (Slp homology domain 1) and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of SlaC2-c are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif. Moreover, Slac2-c has a middle myosin-binding domain and a C-terminal actin-binding domain.

Pssm-ID: 277292 Cd Length: 49 Bit Score: 40.85 E-value: 6.88e-05

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 33301669  63 CARCQEGLGRLIPKSSTCVGCNHLVCRECRVL-ESNGSWRCKVCSKEI 109
Cdd:cd15753   2 CMRCCSPFTFLFNRKRQCRDCKFNVCKSCASYdKKEKGWTCNVCQKQR 49

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

Pssm-ID: 175988 [Multi-domain] Cd Length: 125 Bit Score: 42.26 E-value: 9.91e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 393 KRSNPYVKtyLLPDKsrQGKRKTSIKRDTINPLYDETFRYEISEsllaQRTLQFSVWHHGRFGRNTFLGEAEVHMDSW-- 470
Cdd:cd04021  20 FKPDPYVE--VTVDG--QPPKKTEVSKKTSNPKWNEHFTVLVTP----QSTLEFKVWSHHTLKADVLLGEASLDLSDIlk 91

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 33301669 471 KLDKKLDHC-LPLHgkISTESSpGLPAHKGELVVSL 505
Cdd:cd04021  92 NHNGKLENVkLTLN--LSSENK-GSSVKVGELTVIL 124

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: 42.53 E-value: 1.21e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 529 ELQVWIKEAKNLTAAKSGGTSDSFVKGYLLpmrNKAskRKTPVMKKTLSPHYNHTFVYNGVRL-EDLQHM-------CLE 600
Cdd:cd04017   2 QLRAYIYQARDLLAADKSGLSDPFARVSFL---NQS--QETEVIKETLSPTWDQTLIFDEVELyGSPEEIaqnpplvVVE 76

                        90
                ....*....|....*.
gi 33301669 601 LtvWDREPLASNDFLG 616
Cdd:cd04017  77 L--FDQDSVGKDEFLG 90

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: 42.05 E-value: 1.38e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 531 QVWIKEAKNLTAAKSGGTSDSFVKgyllpMRNKASKRKTPVMKKTLSPHYNH--TFVYNGVRLEDLQHMCLELTVWDREP 608
Cdd:cd08682   2 QVTVLQARGLLCKGKSGTNDAYVI-----IQLGKEKYSTSVKEKTTSPVWKEecSFELPGLLSGNGNRATLQLTVMHRNL 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 33301669 609 LASNDFLGGVRLgvgtgisngEVVDWMDSTGEEVSLWQKMRQYPG 653
Cdd:cd08682  77 LGLDKFLGQVSI---------PLNDLDEDKGRRRTRWFKLESKPG 112

C2 domain found in 5' repressor element under dual repression binding protein-1 (Freud-1); Freud-1 is a novel calcium-regulated repressor that negatively regulates basal 5-HT1A receptor expression in neurons. It may also play a role in the altered regulation of 5-HT1A receptors associated with anxiety or major depression. Freud-1 contains two DM-14 basic repeats, a helix-loop-helix DNA binding domain, and a C2 domain. The Freud-1 C2 domain is thought to be calcium insensitive and it lacks several acidic residues that mediate calcium binding of the PKC C2 domain. In addition, it contains a poly-basic insert that is not present in calcium-dependent C2 domains and may function as a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 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: 176072 [Multi-domain] Cd Length: 155 Bit Score: 41.91 E-value: 2.26e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 398 YVK-TYLLPDKSRQgKRKTSIKRDTINPLYDETFRYEISESLLA-QRT-----LQFSVWHHGRFGR-NTFLGEAEvhmds 469
Cdd:cd08690  28 YVKfEFPYPNEEPQ-SGKTSTIKDTNSPEYNESFKLNINRKHRSfQRVfkrhgLKFEVYHKGGFLRsDKLLGTAQ----- 101

                        90
                ....*....|....
gi 33301669 470 WKLDkKLDHCLPLH 483
Cdd:cd08690 102 VKLE-PLETKCEIH 114

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: 41.11 E-value: 3.12e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 530 LQVWIKEAKNLTAAKSGGTSDSFVKgylLPMRNKA-SKRKTpvMKKTLSPHYNHTFVyngVRLEDL-QHMCLEltVWDRE 607
Cdd:cd04042   2 LDIHLKEGRNLAARDRGGTSDPYVK---FKYGGKTvYKSKT--IYKNLNPVWDEKFT---LPIEDVtQPLYIK--VFDYD 71

                        90
                ....*....|...
gi 33301669 608 PLASNDFLGGVRL 620
Cdd:cd04042  72 RGLTDDFMGSAFV 84

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

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 40.63 E-value: 3.95e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 375 LVIHVKECHQLAYADEAKKrSNPYVKTYLlpdksrQGKR--KTSIKRDTINPLYDETFRYEISESLLAQrtLQFSVWHHG 452
Cdd:cd04040   1 LTVDVISAENLPSADRNGK-SDPFVKFYL------NGEKvfKTKTIKKTLNPVWNESFEVPVPSRVRAV--LKVEVYDWD 71

                        90       100       110
                ....*....|....*....|....*....|...
gi 33301669 453 RFGRNTFLGEAEVHMDSWKLDKKLDHCLPLHGK 485
Cdd:cd04040  72 RGGKDDLLGSAYIDLSDLEPEETTELTLPLDGQ 104

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: 40.23 E-value: 6.02e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 374 TLVIHVKECHQLAYADEAKKrSNPYVKTYLLpdKSRQGKRKTSIKrDTINPLYDEtfRYEISESLLAQRTLQFSVWHHGR 453
Cdd:cd04037   1 LVRVYVVRARNLQPKDPNGK-SDPYLKIKLG--KKKINDRDNYIP-NTLNPVFGK--MFELEATLPGNSILKISVMDYDL 74


                ....*....
gi 33301669 454 FGRNTFLGE 462
Cdd:cd04037  75 LGSDDLIGE 83

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: 9.02e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 33301669  528 GELQVWIKEAKNLTAAKSGGTSDSFVKGYLlpmrNKASKRKTPVMKKTLSPHYNHTFV 585
Cdd:COG5038 1040 GYLTIMLRSGENLPSSDENGYSDPFVKLFL----NEKSVYKTKVVKKTLNPVWNEEFT 1093

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: 9.53e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 534 IKEAKNLTAAKSGGTSDSFVKgyllpMRNKASKR---KTPVMKKTLSPHYNHTFVyngVRLEDLQHMCLELTVWDREPLA 610
Cdd:cd04043   7 IVRAENLKADSSNGLSDPYVT-----LVDTNGKRriaKTRTIYDTLNPRWDEEFE---LEVPAGEPLWISATVWDRSFVG 78


                ....*.
gi 33301669 611 SNDFLG 616
Cdd:cd04043  79 KHDLCG 84

C2 domain second 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: 175994 [Multi-domain] Cd Length: 146 Bit Score: 39.68 E-value: 1.35e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33301669 528 GELQVWIKEAKNLTA-AKSGGTSDSFVKGYLLPMRNKASKRKTPVMKKTLSPHYNHTFVYNgvrlEDLQHMCLELTVW 604
Cdd:cd04028  29 GQLEVEVIRARGLVQkPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFD----VSPTGKTLQVIVW 102

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: 38.76 E-value: 1.88e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 499 GELVVSLKYIPASKlpvggdrkkskggeggELQVWIKEAKNLTAAKSGGTSDSFVKGYLLPmrNKASKRKTPVMKKTlSP 578
Cdd:cd08389   3 GDLDVAFEYDPSAR----------------KLTVTVIRAQDIPTKDRGGASSWQVHLVLLP--SKKQRAKTKVQRGP-NP 63

                        90       100
                ....*....|....*....|...
gi 33301669 579 HYNHTFVYNGVRLEDLQHMCLEL 601
Cdd:cd08389  64 VFNETFTFSRVEPEELNNMALRF 86

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: 37.67 E-value: 3.31e-03

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 33301669 414 KTSIKRDTINPLY-DETFRYEISESLLAQRTLQFSVWHHGRFGRNTFLG 461
Cdd:cd08688  35 KTDVVKKSLNPVWnSEWFRFEVDDEELQDEPLQIRVMDHDTYSANDAIG 83

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: 37.98 E-value: 3.68e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 33301669 394 RSNPYVKTYLLPDKsrqgKRKTSIKRDT-INPLYDETFRYEISESLLAQ--RTLQFSVWHHGRFGRNTFLGEAEV 465
Cdd:cd04051  20 KMKVYAVVWIDPSH----KQSTPVDRDGgTNPTWNETLRFPLDERLLQQgrLALTIEVYCERPSLGDKLIGEVRV 90

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: 37.66 E-value: 3.68e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 375 LVIHVKECHQLAYADEA-----KKRSNPYVKTyllpdksRQGKR--KTSIKRDTINPLYDETFRYEISEslLAQRTLQFS 447
Cdd:cd08391   3 LRIHVIEAQDLVAKDKFvgglvKGKSDPYVIV-------RVGAQtfKSKVIKENLNPKWNEVYEAVVDE--VPGQELEIE 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 33301669 448 VWHHGRfGRNTFLGEAEVHMDSWKLDKKLDHCLPL----HGKI 486
Cdd:cd08391  74 LFDEDP-DKDDFLGRLSIDLGSVEKKGFIDEWLPLedvkSGRL 115

FYVE-related domain found in Rab effector Noc2 and similar proteins; Rab effector Noc2, also termed No C2 domains protein, or rabphilin-3A-like protein (RPH3AL), is a Rab3 effector that mediates the regulation of secretory vesicle exocytosis in neurons and certain endocrine cells. It also functions as a Rab27 effector and is involved in isoproterenol (IPR)-stimulated amylase release from acinar cells. Noc2 contains an N-terminal Rab3A effector domain which harbors a conserved zinc finger, but lacks tandem C2 domains. The FYVE domain of Noc2 resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.

Pssm-ID: 277302 Cd Length: 64 Bit Score: 36.10 E-value: 4.05e-03

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 33301669  63 CARCQEGLGRLIPKSSTCVGCNHLVCRECRVlESNGS-----WRCKVCSKEIELKK 113
Cdd:cd15763  10 CLLCGELLGFLGSSSVFCQDCRKKVCTKCGI-ETSGSqkrplWLCKICSEQREVWK 64

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: 37.75 E-value: 5.07e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 375 LVIHVKECHQLAYADeAKKRSNPYVKTYLlpdksRQGKRKTSIKRDTINPLYDETFRYEISEslLAQRTLQFSVWHHGRF 454
Cdd:cd08375  17 LMVVIVEGRDLKPCN-SNGKSDPYCEVSM-----GSQEHKTKVVSDTLNPKWNSSMQFFVKD--LEQDVLCITVFDRDFF 88

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 33301669 455 GRNTFLGEAEVHMDSWKLDKKlDHCLPLHGKISTESSPglpahKGELVVSL 505
Cdd:cd08375  89 SPDDFLGRTEIRVADILKETK-ESKGPITKRLLLHEVP-----TGEVVVKL 133

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: 37.23 E-value: 6.30e-03

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 33301669 412 KRKTSIKRDTINPLYDETFRYEISESLLAQRTLQFSVWHHGRFGRNTFLGEAEV 465
Cdd:cd08373  27 KKKTRVLENELNPVWNETFEWPLAGSPDPDESLEIVVKDYEKVGRNRLIGSATV 80

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: 37.24 E-value: 6.33e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 528 GELQVWIKEAKNLTAaksggtsDSFVK--GYLLPMRNKASKRkTPVMKKTLSPHYNHTFVYNGVRLEDLQHMCLEltVWD 605
Cdd:cd04032  28 ATLTVTVLRATGLWG-------DYFTStdGYVKVFFGGQEKR-TEVIWNNNNPRWNATFDFGSVELSPGGKLRFE--VWD 97

                        90
                ....*....|.
gi 33301669 606 REPLASNDFLG 616
Cdd:cd04032  98 RDNGWDDDLLG 108

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: 36.76 E-value: 9.86e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33301669 375 LVIHVKECHQLAYADEAKKRSNPYVKTyllpdkSRQGKR---KTSIKRDTINPLYDETFRYEIseSLLAQRtLQFSVWHH 451
Cdd:cd04044   4 LAVTIKSARGLKGSDIIGGTVDPYVTF------SISNRRelaRTKVKKDTSNPVWNETKYILV--NSLTEP-LNLTVYDF 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33301669 452 GRFGRNTFLGEAEVHMDSWKLDKKLDHC---LPLHGKIstesspglpahKGELVVSLKYIP 509
Cdd:cd04044  75 NDKRKDKLIGTAEFDLSSLLQNPEQENLtknLLRNGKP-----------VGELNYDLRFFP 124