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 111600247 306 TGEIEFAIHYCVKSCSLEICIKTCKNLAYGEEKKRKCNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVDPGQ 385
Cdd:cd08392    1 TGEIEFALHYNFRTSCLEITIKACRNLAYGDEKKKKCHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 111600247 386 LMTRRLQVSVWHLGTLARRVFLGEVILPLAMWDFKDSTAQNARWYPLR 433
Cdd:cd08392   81 LSSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFEDTDSQRFLWYPLN 128

FYVE domain like superfamily; FYVE domain is a 60-80 residue double zinc finger motif-containing module named after the four proteins, Fab1, YOTB, Vac1, and EEA1. The canonical FYVE domains are distinguished from other zinc fingers by 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, which form a compact phosphatidylinositol 3-phosphate (PtdIns3P, also termed PI3P)-binding site. They are found in many membrane trafficking regulators, including EEA1, Hrs, Vac1p, Vps27p, and FENS-1, which locate to early endosomes, specifically bind PtdIns3P, and play important roles in vesicular traffic and in signal transduction. Some proteins, such as rabphilin-3A and alpha-Rab3-interacting molecules (RIMs), are also involved in membrane trafficking and bind to members of the Rab subfamily of GTP hydrolases. However, they contain FYVE-related domains that are structurally similar to the canonical FYVE domains but lack the three signature sequences. At this point, they may not bind to phosphoinositides. In addition, this superfamily also contains the third group of proteins, caspase-associated ring proteins CARP1 and CARP2. They do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10, which are distinguished from other FYVE-type proteins. Moreover, these proteins have an altered sequence in the basic ligand binding patch and lack the WxxD motif that is conserved only in phosphoinositide binding FYVE domains. Thus they constitute a family of unique FYVE-type domains called FYVE-like domains. The FYVE domain is structurally similar to the RING domain and the PHD finger. This superfamily also includes ADDz zinc finger domain, which is a PHD-like zinc finger motif that contains two parts, a C2-C2 and a PHD-like zinc finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 111600247  60 EKCRARCQRALGLLLNRGAVCQGCSHRVCSECRVFLRRtRAWKCTVCFE 108
Cdd:cd15765    1 ERSCARCQKPLGKLLNRGAVCNGCSHRVCSECRVFLGR-EIWKCTVCHA 48

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 111600247 306 TGEIEFAIHYCVKSCSLEICIKTCKNLAYGEEKKRKCNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVDPGQ 385
Cdd:cd08392    1 TGEIEFALHYNFRTSCLEITIKACRNLAYGDEKKKKCHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 111600247 386 LMTRRLQVSVWHLGTLARRVFLGEVILPLAMWDFKDSTAQNARWYPLR 433
Cdd:cd08392   81 LSSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFEDTDSQRFLWYPLN 128

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 111600247  60 EKCRARCQRALGLLLNRGAVCQGCSHRVCSECRVFLRRtRAWKCTVCFE 108
Cdd:cd15765    1 ERSCARCQKPLGKLLNRGAVCNGCSHRVCSECRVFLGR-EIWKCTVCHA 48

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 111600247   14 ERDIILRVLYRDQTVQSTEEERVRKLKshlQHLRWKGAK----SSSQEYKEKCRARCQRALGLLLNRGAVCQGCSHRVCS 89
Cdd:pfam02318   7 EAEHVWEVVQRDFDLRKKEEERLGELK---GKLDKESSKrellGNQAHLGETHCIRCLQPFGFLVNSKRQCLDCRKNVCK 83

                          90       100       110
                  ....*....|....*....|....*....|....
gi 111600247   90 ECRVFLRRTRAWKCTVCFEDRNVKIKTGEWFFEE 123
Cdd:pfam02318  84 KCGVYNKPEQGWLCDPCSEARELKKGSLEWFYKN 117

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247  477 GQLCLVVLGAKNLPVRSD-GTLNSFVKGCLtlpNQQKLRVKSPVLKKQACPQWKHSFVFNgVSSSQlrQSTLELTVWDQA 555
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGnGTSDPYVKVYL---LDGKQKKKTKVVKNTLNPVWNETFTFS-VPDPE--NAVLEIEVYDYD 74

                          90
                  ....*....|....*
gi 111600247  556 IFGMNDrLLGEARLG 570
Cdd:pfam00168  75 RFGRDD-FIGEVRIP 88

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 111600247 306 TGEIEFAIHYCVKSCSLEICIKTCKNLAYGEEKKRKCNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVDPGQ 385
Cdd:cd08392    1 TGEIEFALHYNFRTSCLEITIKACRNLAYGDEKKKKCHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYVVEADL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 111600247 386 LMTRRLQVSVWHLGTLARRVFLGEVILPLAMWDFKDSTAQNARWYPLR 433
Cdd:cd08392   81 LSSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFEDTDSQRFLWYPLN 128

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 111600247 447 NGELAVRAKLVLPAGPRKpqeaQEGQLALNGQLCLVVLGAKNLP-VRSDGTLNSFVKGCLTLPNQQKLRVKSPVLKKQAC 525
Cdd:cd04020    1 RGELKVALKYVPPESEGA----LKSKKPSTGELHVWVKEAKNLPaLKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVN 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247 526 PQWKHSFVFNGVSSSQLRQSTLELTVWDQAIFGMNDrLLGEARLG-----SKGGAAGCPDSGSQSKLQWHRVLSSPNLWT 600
Cdd:cd04020   77 PVWNHTFVYDGVSPEDLSQACLELTVWDHDKLSSND-FLGGVRLGlgtgkSYGQAVDWMDSTGEEILLWQKMLDNPNSWV 155

                 ....*..
gi 111600247 601 DMTLVLH 607
Cdd:cd04020  156 EGTLPLR 162

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 111600247 307 GEIEFAIHYCVKSCSLEICIKTCKNLAYGEEKKRKCNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVDPGQL 386
Cdd:cd08393    2 GSVQFALDYDPKLRELHVHVIQCQDLAAADPKKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKVEREEL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 111600247 387 MTRRLQVSVWHLGTLARRVFLGEVILPLAMWDFkDSTAQNarWYPLR 433
Cdd:cd08393   82 PTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDW-SNTQPT--WYPLQ 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247 305 VTGEIEFAIHYCVKSCSLEICIKTCKNLAyGEEKKRKCNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVDPG 384
Cdd:cd04030    1 PLGRIQLTIRYSSQRQKLIVTVHKCRNLP-PCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLE 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 111600247 385 QLMTRRLQVSVWHLGTLA--RRVFLGEVILPLAMWDFKDSTAQnarWYPLR 433
Cdd:cd04030   80 ELKRRTLDVAVKNSKSFLsrEKKLLGQVLIDLSDLDLSKGFTQ---WYDLT 127

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 111600247  60 EKCRARCQRALGLLLNRGAVCQGCSHRVCSECRVFLRRtRAWKCTVCFE 108
Cdd:cd15765    1 ERSCARCQKPLGKLLNRGAVCNGCSHRVCSECRVFLGR-EIWKCTVCHA 48

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 111600247   14 ERDIILRVLYRDQTVQSTEEERVRKLKshlQHLRWKGAK----SSSQEYKEKCRARCQRALGLLLNRGAVCQGCSHRVCS 89
Cdd:pfam02318   7 EAEHVWEVVQRDFDLRKKEEERLGELK---GKLDKESSKrellGNQAHLGETHCIRCLQPFGFLVNSKRQCLDCRKNVCK 83

                          90       100       110
                  ....*....|....*....|....*....|....
gi 111600247   90 ECRVFLRRTRAWKCTVCFEDRNVKIKTGEWFFEE 123
Cdd:pfam02318  84 KCGVYNKPEQGWLCDPCSEARELKKGSLEWFYKN 117

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 111600247 307 GEIEFAIHYCVKSCSLEICIKTCKNLAYGEEKKRKCNPYVKTYLLPD--RSSQgkrkTRVQKNTLDPTFEETLKYQVDPG 384
Cdd:cd08390    1 GRLWFSVQYDLEEEQLTVSLIKARNLPPRTKDVAHCDPFVKVCLLPDerRSLQ----SKVKRKTQNPNFDETFVFQVSFK 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 111600247 385 QLMTRRLQVSVWHLGTLARRVFLGEVILPLAmwDFkDSTAQNARWYPLR 433
Cdd:cd08390   77 ELQRRTLRLSVYDVDRFSRHCIIGHVLFPLK--DL-DLVKGGVVWRDLE 122

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 111600247   321 SLEICIKTCKNLAyGEEKKRKCNPYVKTYLLPDRSSqgKRKTRVQKNTLDPTFEETLKYQVDPGQLmtRRLQVSVWHLGT 400
Cdd:smart00239   1 TLTVKIISARNLP-PKDKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPEL--AELEIEVYDKDR 75

                           90
                   ....*....|....
gi 111600247   401 LARRVFLGEVILPL 414
Cdd:smart00239  76 FGRDDFIGQVTIPL 89

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247 307 GEIEFAIHYCVKSCSLEICIKTCKNLAYGEEKKRKCNPYVKTYLLPDRssQGKRKTRVQKNTLDPTFEETLK-YQVDPGQ 385
Cdd:cd08388    3 GTLFFSLRYNSEKKALLVNIIECRDLPAMDEQSGTSDPYVKLQLLPEK--EHKVKTRVLRKTRNPVYDETFTfYGIPYNQ 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 111600247 386 LMTRRLQVSVWHLGTLARRVFLGEVILPLA 415
Cdd:cd08388   81 LQDLSLHFAVLSFDRYSRDDVIGEVVCPLA 110

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 111600247 344 PYVKTYLLPDRssqgKRK--TRVQKNTLDPTFEETLKYQVDPGQLMTRRLQVSVWHLGTLARRVFLGEVILPLAMWDF 419
Cdd:cd08385   39 PYVKVYLLPDK----KKKfeTKVHRKTLNPVFNETFTFKVPYSELGNKTLVFSVYDFDRFSKHDLIGEVRVPLLTVDL 112

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 111600247 307 GEIEFAIHYcvKSCSLEICIKTCKNL----AYGEEkkrkcNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVD 382
Cdd:cd04026    2 GRIYLKISV--KDNKLTVEVREAKNLipmdPNGLS-----DPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLK 74

                         90
                 ....*....|....
gi 111600247 383 PGQLmTRRLQVSVW 396
Cdd:cd04026   75 PADK-DRRLSIEVW 87

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247  477 GQLCLVVLGAKNLPVRSD-GTLNSFVKGCLtlpNQQKLRVKSPVLKKQACPQWKHSFVFNgVSSSQlrQSTLELTVWDQA 555
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGnGTSDPYVKVYL---LDGKQKKKTKVVKNTLNPVWNETFTFS-VPDPE--NAVLEIEVYDYD 74

                          90
                  ....*....|....*
gi 111600247  556 IFGMNDrLLGEARLG 570
Cdd:pfam00168  75 RFGRDD-FIGEVRIP 88

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 111600247 307 GEIEFAIHYCVKSCSLEICIKTCKNLaygeeKKRKC----NPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVD 382
Cdd:cd08402    2 GDICFSLRYVPTAGKLTVVILEAKNL-----KKMDVgglsDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFEVP 76

                         90       100       110
                 ....*....|....*....|....*....|
gi 111600247 383 PGQLMTRRLQVSVWHLGTLARRVFLGEVIL 412
Cdd:cd08402   77 FEQIQKVHLIVTVLDYDRIGKNDPIGKVVL 106

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+.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247 307 GEIEFAIHYcvKSCSLEICIKTCKNLAYGEEKKRKCNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVDPGQl 386
Cdd:cd04028   18 GDIQLGLYD--KKGQLEVEVIRARGLVQKPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDVSPTG- 94

                         90       100
                 ....*....|....*....|...
gi 111600247 387 mtRRLQVSVW-HLGTLARRVFLG 408
Cdd:cd04028   95 --KTLQVIVWgDYGRMDKKVFMG 115

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247 307 GEIEFAIHYCVKSCSLEICIKTCKNLAyGEEKKRKCNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQ-VDPGQ 385
Cdd:cd04035    2 GTLEFTLLYDPANSALHCTIIRAKGLK-AMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYgITEED 80

                         90       100
                 ....*....|....*....|....*....
gi 111600247 386 LMTRRLQVSVWHLGTLaRRVFLGEVILPL 414
Cdd:cd04035   81 IQRKTLRLLVLDEDRF-GNDFLGETRIPL 108

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247 307 GEIEFAIHYCVKSCSLEICIKTCKNLAyGEEKKRKCNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVDPGQL 386
Cdd:cd08403    1 GELMFSLCYLPTAGRLTLTIIKARNLK-AMDITGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFDVPPENV 79

                 ....*....
gi 111600247 387 MTRRLQVSV 395
Cdd:cd08403   80 DNVSLIIAV 88

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247 307 GEIEFAIHYCVKSCSLEICIKTCKNLAYGEEKKrKCNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVDPGQL 386
Cdd:cd08406    2 GEILLSLSYLPTAERLTVVVVKARNLVWDNGKT-TADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFSVPAIVL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 111600247 387 MTRRLQVSVWHLGTLARRVFLGEVIL-------PLAMWDFKDSTAQN--ARWYPLR 433
Cdd:cd08406   81 QDLSLRVTVAESTEDGKTPNVGHVIIgpaasgmGLSHWNQMLASLRKpvAMWHPLR 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247 342 CNPYVK-TYLLPDRSSQgkRKTRVQKNTLDPTFEETLKYQVDPGQLMTRR-------------LQVSVWHLGTLARRVFL 407
Cdd:cd08675   19 CDPFARvTLNYSSKTDT--KRTKVKKKTNNPRFDEAFYFELTIGFSYEKKsfkveeedlekseLRVELWHASMVSGDDFL 96

                         90       100
                 ....*....|....*....|....*
gi 111600247 408 GEVILPLAMwdfKDSTAQNARWYPL 432
Cdd:cd08675   97 GEVRIPLQG---LQQAGSHQAWYFL 118

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 111600247 307 GEIEFAIHYCVKSCSLEICIKTCKNLAYGEEKkRKCNPYVKTYLLPDRSSQGKRKTRVQKNTLDPTFEETLKYQVDPGQL 386
Cdd:cd00276    1 GELLLSLSYLPTAERLTVVVLKARNLPPSDGK-GLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQL 79

                         90       100
                 ....*....|....*....|....*.
gi 111600247 387 MTRRLQVSVWHLGTLARRVFLGEVIL 412
Cdd:cd00276   80 EEVSLVITVVDKDSVGRNEVIGQVVL 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 111600247 475 LNGQLCLVVLGAKNL-PVRSDGTLNSFVKGCLTLPNQQKLRVKSPVLKKQACPQWKHSFVFNgVSSSQLRQSTLELTVWD 553
Cdd:cd08405   13 TANRITVNIIKARNLkAMDINGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFN-IPLERLRETTLIITVMD 91

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 111600247 554 QAIFGMNDrLLGEARLGSKGGAAGCP------DSGSQSKLQWHRV 592
Cdd:cd08405   92 KDRLSRND-LIGKIYLGWKSGGLELKhwkdmlSKPRQPVAQWHRL 135

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 111600247 478 QLCLVVLGAKNLPVRSDG--TLNSFVKGCLtLPNQQklRVKSPVLKKQAC-PQWKHSFVFNgVSSSQLRQSTLELTVWD 553
Cdd:cd08390   15 QLTVSLIKARNLPPRTKDvaHCDPFVKVCL-LPDER--RSLQSKVKRKTQnPNFDETFVFQ-VSFKELQRRTLRLSVYD 89

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 111600247  64 ARCQRALGLLLNRGAVCQGCSHRVCSECRVFLRRTRAWKCTVCFEDRNVKIKTGEWFFEERARKF 128
Cdd:cd15752    4 ARCLQPFQFLLNSGRQCLDCGLRTCKSCSRYHPEEQGWVCDPCHLARVVKIGSLEWYYNHVRARF 68