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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 498 KGELVVSLKYIPASKPPvggdRKKSKGGEGGELQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKAGKRKTPVMKKTLN 577
Cdd:cd04020     1 RGELKVALKYVPPESEG----ALKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVN 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 578 PHYNHTFVYNGVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGVGTGISNGEVVDWMDSTGEEVSLWQKMRQYPGSWAE 657
Cdd:cd04020    77 PVWNHTFVYDGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDWMDSTGEEILLWQKMLDNPNSWVE 156

                  ....*.
gi 2493543040 658 GTLQLR 663
Cdd:cd04020   157 GTLPLR 162

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2493543040  58 YSDRTCARCQESLGRLSPKTNTCRGCNHLVCRDCRIQESNGTWRCKVCAK 107
Cdd:cd15764     1 YSERSCGRCQESLGRLSPKANQCRGCNHLVCRDCRAVRPNGSWVCSVCAK 50

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 498 KGELVVSLKYIPASKPPvggdRKKSKGGEGGELQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKAGKRKTPVMKKTLN 577
Cdd:cd04020     1 RGELKVALKYVPPESEG----ALKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVN 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 578 PHYNHTFVYNGVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGVGTGISNGEVVDWMDSTGEEVSLWQKMRQYPGSWAE 657
Cdd:cd04020    77 PVWNHTFVYDGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDWMDSTGEEILLWQKMLDNPNSWVE 156

                  ....*.
gi 2493543040 658 GTLQLR 663
Cdd:cd04020   157 GTLPLR 162

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2493543040  58 YSDRTCARCQESLGRLSPKTNTCRGCNHLVCRDCRIQESNGTWRCKVCAK 107
Cdd:cd15764     1 YSERSCGRCQESLGRLSPKANQCRGCNHLVCRDCRAVRPNGSWVCSVCAK 50

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 528 GELQVWIKEAKNLTAAKAGGTSDSFVKGYLLpmrNKAGKRKTPVMKKTLNPHYNHTFVYNgvrLEDLQHMCLELTVWDRE 607
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFS---VPDPENAVLEIEVYDYD 74

                          90       100
                  ....*....|....*....|....*....
gi 2493543040 608 PLASNDFLGGVRLGVGTGISNGEVVDWMD 636
Cdd:pfam00168  75 RFGRDDFIGEVRIPLSELDSGEGLDGWYP 103

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040  374 SLVVHVKECHQLAYADEAKKrSNPYVKTYLLPDKSRqgKRKTSIKRDTINPLYDETLRYEIPESLLaqRTLQFSVWHHGR 453
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGK-SDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPEL--AELEIEVYDKDR 75

                           90       100
                   ....*....|....*....|....*.
gi 2493543040  454 FGRNTFLGEAEIQMDSWKLDKKLDHC 479
Cdd:smart00239  76 FGRDDFIGQVTIPLSDLLLGGRHEKL 101

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2493543040  528 GELQVWIKEAKNLTAAKAGGTSDSFVKGYLlpmrNKAGKRKTPVMKKTLNPHYNHTFV 585
Cdd:COG5038   1040 GYLTIMLRSGENLPSSDENGYSDPFVKLFL----NEKSVYKTKVVKKTLNPVWNEEFT 1093

Protein present in Fab1, YOTB, Vac1, and EEA1; The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2493543040   63 CARCQESLGRLSPKTNtCRGCNHLVCRDC-----RIQESNGTWRCKVC 105
Cdd:smart00064  13 CMGCGKEFNLTKRRHH-CRNCGRIFCSKCsskkaPLPKLGIERPVRVC 59

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 498 KGELVVSLKYIPASKPPvggdRKKSKGGEGGELQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKAGKRKTPVMKKTLN 577
Cdd:cd04020     1 RGELKVALKYVPPESEG----ALKSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVN 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 578 PHYNHTFVYNGVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGVGTGISNGEVVDWMDSTGEEVSLWQKMRQYPGSWAE 657
Cdd:cd04020    77 PVWNHTFVYDGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDWMDSTGEEILLWQKMLDNPNSWVE 156

                  ....*.
gi 2493543040 658 GTLQLR 663
Cdd:cd04020   157 GTLPLR 162

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 360 GRIAFSLKYEQQTQSLVVHVKECHQLAYADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETLRYEIPESLL 439
Cdd:cd08521     1 GEIEFSLSYNYKTGSLEVHIKECRNLAYADEKKKRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYHISKSQL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2493543040 440 AQRTLQFSVWHHGRFGRNTFLGEAEIQMDSWKLDKKLDHCLPL 482
Cdd:cd08521    81 ETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 359 TGRIAFSLKYEQQTQSLVVHVKECHQLAYADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETLRYEIPESL 438
Cdd:cd08392     1 TGEIEFALHYNFRTSCLEITIKACRNLAYGDEKKKKCHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADL 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2493543040 439 LAQRTLQFSVWHHGRFGRNTFLGEAEIQMDSWKLDKK 475
Cdd:cd08392    81 LSSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFEDT 117

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 359 TGRIAFSLKYEQQTQS-LVVHVKECHQLAYADeakkrSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETLRYE-IPE 436
Cdd:cd08381     1 GGQVKLSISYKNGTLFvMVMHAKNLPLLDGSD-----PDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDgLPV 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2493543040 437 SLLAQRTLQFSVWHHGRFGRNTFLGEAEIQMDSWKLDKKLDHCLPL 482
Cdd:cd08381    76 EDLQQRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPL 121

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 361 RIAFSLKYEQQTQSLVVHVKECHQLAYADeAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETLRYEIPESLLA 440
Cdd:cd08384     1 KILVSLMYNTQRRGLIVGIIRCVNLAAMD-ANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLA 79

                          90       100
                  ....*....|....*....|....*....
gi 2493543040 441 QRTLQFSVWHHGRFGRNTFLGEAEIQMDS 469
Cdd:cd08384    80 KKTLEITVWDKDIGKSNDYIGGLQLGINA 108

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 528 GELQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKAGKRKTPVMKKTLNPHYNHTFVYNgVRLEDLQHMCLELTVWDRE 607
Cdd:cd08384    13 RGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYD-IKHSDLAKKTLEITVWDKD 91

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2493543040 608 PLASNDFLGGVRLGVgtgisngevvdwmDSTGEEVSLWQKMRQYPG 653
Cdd:cd08384    92 IGKSNDYIGGLQLGI-------------NAKGERLRHWLDCLKNPD 124

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 498 KGELVVSLKYIPASKppvggdrkkskggeggELQVWIKEAKNLTAAKA-GGTSDSFVKGYLLPMRNKAGKRKTPVMKKTL 576
Cdd:cd08393     1 QGSVQFALDYDPKLR----------------ELHVHVIQCQDLAAADPkKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTL 64

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2493543040 577 NPHYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRLGVGT 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 360 GRIAFSLKYEQQTQSLVVHVKECHQLAYADEAKKRSNPYVKTYLLPDKSRQgkRKTSIKRDTINPLYDETLRYEIPESLL 439
Cdd:cd08390     1 GRLWFSVQYDLEEEQLTVSLIKARNLPPRTKDVAHCDPFVKVCLLPDERRS--LQSKVKRKTQNPNFDETFVFQVSFKEL 78

                          90       100
                  ....*....|....*....|....
gi 2493543040 440 AQRTLQFSVWHHGRFGRNTFLGEA 463
Cdd:cd08390    79 QRRTLRLSVYDVDRFSRHCIIGHV 102

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+.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 525 GEGGELQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKAGKRKTPVMKKTLNPHYNHTFVYNGVRLEDLQHMCLELTVW 604
Cdd:cd04031    13 KVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRETLKERTLEVTVW 92

                          90       100
                  ....*....|....*....|....*.
gi 2493543040 605 DREPLASNDFLGGVRLGVGTGISNGE 630
Cdd:cd04031    93 DYDRDGENDFLGEVVIDLADALLDDE 118

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 499 GELVVSLKYIPASkppvggdrkkskggegGELQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKAGKRKTPVMKKTLNP 578
Cdd:cd08402     2 GDICFSLRYVPTA----------------GKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNP 65

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2493543040 579 HYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRLgvGTGISNGEVVDWMD 636
Cdd:cd08402    66 YYNESFSFE-VPFEQIQKVHLIVTVLDYDRIGKNDPIGKVVL--GCNATGAELRHWSD 120

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 526 EGGELQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKAGKRKTPVMKKTLNPHYNHTFVYNgVRLEDLqHMCLELTVWD 605
Cdd:cd04026    11 KDNKLTVEVREAKNLIPMDPNGLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFD-LKPADK-DRRLSIEVWD 88

                          90
                  ....*....|....*...
gi 2493543040 606 REPLASNDFLGGVRLGVG 623
Cdd:cd04026    89 WDRTTRNDFMGSLSFGVS 106

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 360 GRIAFSLKYEQQTQSLVVHVKECHQLAyADEAKKRSNPYVKTYLLPDKSRqgKRKTSIKRDTINPLYDETLRYE-IPESL 438
Cdd:cd08386     3 GRIQFSVSYDFQESTLTLKILKAVELP-AKDFSGTSDPFVKIYLLPDKKH--KLETKVKRKNLNPHWNETFLFEgFPYEK 79

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2493543040 439 LAQRTLQFSVWHHGRFGRNTFLGEAEIQMDSWKL 472
Cdd:cd08386    80 LQQRVLYLQVLDYDRFSRNDPIGEVSLPLNKVDL 113

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 530 LQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRnkagKRKTPVMKKTLNPHYNHTFVYNgvrLEDLQHMCLELTVWDREPL 609
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGKQ----KFKTKVVKNTLNPVWNETFEFP---VLDPESDTLTVEVWDKDRF 73

                          90       100
                  ....*....|....*....|....
gi 2493543040 610 ASNDFLGGVRLGVGTGISNGEVVD 633
Cdd:cd00030    74 SKDDFLGEVEIPLSELLDSGKEGE 97

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 499 GELVVSLKYipaskppvggDRKKskggegGELQVWIKEAKNLTAAKAG-GTSDSFVKGYLLPMRNKAGKRKTPVMKKTLN 577
Cdd:cd08521     1 GEIEFSLSY----------NYKT------GSLEVHIKECRNLAYADEKkKRSNPYVKVYLLPDKSKQSKRKTSVKKNTTN 64

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2493543040 578 PHYNHTFVYNgVRLEDLQHMCLELTVWDREPLASNDFLGGVRL 620
Cdd:cd08521    65 PVFNETLKYH-ISKSQLETRTLQLSVWHHDRFGRNTFLGEVEI 106

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040   8 SFLSEEEKDLILGVLQRDEEVRKADEKRIRRLKNEL-LEIKRKGAKRGSQHYSDRTCARCQESLGRLSPKTNTCRGCNHL 86
Cdd:pfam02318   1 SKLTDEEAEHVWEVVQRDFDLRKKEEERLGELKGKLdKESSKRELLGNQAHLGETHCIRCLQPFGFLVNSKRQCLDCRKN 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2493543040  87 VCRDCRIQESNGT-WRCKVCAKEIELKKATGDWFYD 121
Cdd:pfam02318  81 VCKKCGVYNKPEQgWLCDPCSEARELKKGSLEWFYK 116

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040  530 LQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKagKRKTPVMKKTLNPHYNHTFVYNgvrLEDLQHMCLELTVWDREPL 609
Cdd:smart00239   2 LTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFE---VPPPELAELEIEVYDKDRF 76

                           90       100
                   ....*....|....*....|....*
gi 2493543040  610 ASNDFLGGVRLGVGTGISNGEVVDW 634
Cdd:smart00239  77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 360 GRIAFSLKYEQQTQSLVVHVKECHQLAyADEAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETLRYEIPESLL 439
Cdd:cd00276     1 GELLLSLSYLPTAERLTVVVLKARNLP-PSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQL 79

                          90       100
                  ....*....|....*....|....*.
gi 2493543040 440 AQRTLQFSVWHHGRFGRNTFLGEAEI 465
Cdd:cd00276    80 EEVSLVITVVDKDSVGRNEVIGQVVL 105

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 528 GELQVWIKEAKNLTAAKAGGTSDSFVKGYLLPMRNKagKRKTPVMKKTLNPHYNHTFVYNgVRLEDLQHMCLELTVWDRE 607
Cdd:cd08385    16 NQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKK--KFETKVHRKTLNPVFNETFTFK-VPYSELGNKTLVFSVYDFD 92

                          90       100
                  ....*....|....*....|....*....
gi 2493543040 608 PLASNDFLGGVRLGVGTGISNGEVVDWMD 636
Cdd:cd08385    93 RFSKHDLIGEVRVPLLTVDLGHVTEEWRD 121

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2493543040 360 GRIAFSLKYEQQTQSLVVHVKECHQLAYADeAKKRSNPYVKTYLLPDKSRQGKRKTSIKRDTINPLYDETLRYEIPESLL 439
Cdd:cd08402     2 GDICFSLRYVPTAGKLTVVILEAKNLKKMD-VGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVPFEQI 80

                          90       100
                  ....*....|....*....|...
gi 2493543040 440 AQRTLQFSVWHHGRFGRNTFLGE 462
Cdd:cd08402    81 QKVHLIVTVLDYDRIGKNDPIGK 103