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 2217396593 490 KGELTVVLRYIPPEENLMLppeqlqgnktfkkgkkkESPVISGGILEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKA 569
Cdd:cd04020     1 RGELKVALKYVPPESEGAL-----------------KSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKK 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217396593 570 TKHKTLVIKKSVNPQWNHTFMFSGIHPQDIKNVCLELTIWDKEAFSSNIFLGGVRLNSGSGVSHGKNVDWMDSQGEEQRL 649
Cdd:cd04020    64 SKQKTPVVKKSVNPVWNHTFVYDGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDWMDSTGEEILL 143

                         170
                  ....*....|....*....
gi 2217396593 650 WQKMANNPGTPFEGVLMLR 668
Cdd:cd04020   144 WQKMLDNPNSWVEGTLPLR 162

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2217396593  62 RVCVHCHRNLGLIFDRGDPCQACSLRVCRECRVAGPNGSWKCTVCDK 108
Cdd:cd15766     1 RLCVRCLKNLGLIFDRGDLCQECQLRVCSECRVLGANGKWKCTVCAK 47

AF-4 proto-oncoprotein N-terminal region; This family consists of AF4 (Proto-oncogene AF4) and FMR2 (Fragile X E mental retardation syndrome) nuclear proteins. These proteins have been linked to human diseases such as acute lymphoblastic leukaemia and mental retardation. The family also contains a Drosophila AF4 protein homolog Lilliputian which contains an AT-hook domain. Lilliputian represents a novel pair-rule gene that acts in cytoskeleton regulation, segmentation and morphogenesis in Drosophila.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217396593 218 HFRSLKSPPGSdrGSTGSSDLNDQEPGPRTpKSSRSNGVTPGTQSSPAPST--RTVTSVISREYGFENSMDLAAIEGTSQ 295
Cdd:pfam05110 109 HSQPMGPPSSS--SPSVSSSQSQKKSQART-EPAHGGHSSSGSQSSQRSQGqsRSKGGQESHSSSHHKRQERREDLFSCA 185

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217396593 296 ELTKSHRRNTSGTPSIAVSGTSLSSDQSRSELDLSESFTEDSEDTVSIRSKSvPGALDKDSLE-ETEESIDALVSSQLST 374
Cdd:pfam05110 186 SLSHSLEELSPLLSSLSSPVKPLSPSHSRQHTGSKAQNSSDHHGKEYSHSKS-PRDSEAGSHGpESPSTSLLASSSQLSS 264

                         170
                  ....*....|....*...
gi 2217396593 375 NThrLASGLSttSLNSMM 392
Cdd:pfam05110 265 QT--FPPSLP--SKTSAM 278

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 2217396593 490 KGELTVVLRYIPPEENLMLppeqlqgnktfkkgkkkESPVISGGILEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKA 569
Cdd:cd04020     1 RGELKVALKYVPPESEGAL-----------------KSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKK 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217396593 570 TKHKTLVIKKSVNPQWNHTFMFSGIHPQDIKNVCLELTIWDKEAFSSNIFLGGVRLNSGSGVSHGKNVDWMDSQGEEQRL 649
Cdd:cd04020    64 SKQKTPVVKKSVNPVWNHTFVYDGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDWMDSTGEEILL 143

                         170
                  ....*....|....*....
gi 2217396593 650 WQKMANNPGTPFEGVLMLR 668
Cdd:cd04020   144 WQKMLDNPNSWVEGTLPLR 162

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 2217396593  62 RVCVHCHRNLGLIFDRGDPCQACSLRVCRECRVAGPNGSWKCTVCDK 108
Cdd:cd15766     1 RLCVRCLKNLGLIFDRGDLCQECQLRVCSECRVLGANGKWKCTVCAK 47

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 2217396593  534 ILEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKatKHKTLVIKKSVNPQWNHTFMFSGIHPQDiknVCLELTIWDKEA 613
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPEL---AELEIEVYDKDR 75

                           90
                   ....*....|...
gi 2217396593  614 FSSNIFLGGVRLN 626
Cdd:smart00239  76 FGRDDFIGQVTIP 88

C2 domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217396593 423 LYIFVKNCRNLAIGDeKKQRTDAYVKSYLLPDKSrnnKRKTKIRTGT-NPEFNETLKVEFAPD 484
Cdd:pfam00168   3 LTVTVIEAKNLPPKD-GNGTSDPYVKVYLLDGKQ---KKKTKVVKNTlNPVWNETFTFSVPDP 61

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217396593  507 MLPPEQLQGNKTFKKGKKKESPVisgGILEVFIKEAKNLTavKSGGTSDSFVKGYLLPDDSKATKHKTLVIKKSVNPQWN 586
Cdd:COG5038    413 LLPPNSLTIDISQIMAGDSGTAI---GVVEVKIKSAEGLK--KSDSTINGTVDPYITVTFSDRVIGKTRVKKNTLNPVWN 487

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 2217396593  587 HTFmFSGIHPQDIKnvcLELTIWDKEAFSSNIFLGGVRLN 626
Cdd:COG5038    488 ETF-YILLNSFTDP---LNLSLYDFNSFKSDKVVGSTQLD 523

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 2217396593 490 KGELTVVLRYIPPEENLMLppeqlqgnktfkkgkkkESPVISGGILEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKA 569
Cdd:cd04020     1 RGELKVALKYVPPESEGAL-----------------KSKKPSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKK 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217396593 570 TKHKTLVIKKSVNPQWNHTFMFSGIHPQDIKNVCLELTIWDKEAFSSNIFLGGVRLNSGSGVSHGKNVDWMDSQGEEQRL 649
Cdd:cd04020    64 SKQKTPVVKKSVNPVWNHTFVYDGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDWMDSTGEEILL 143

                         170
                  ....*....|....*....
gi 2217396593 650 WQKMANNPGTPFEGVLMLR 668
Cdd:cd04020   144 WQKMLDNPNSWVEGTLPLR 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2217396593 408 GEILLHISYCYKTGGLYIFVKNCRNLAIGDEKKQRTDAYVKSYLLPDKSRNNKRKTKIRTGT-NPEFNETLK 478
Cdd:cd08521     1 GEIEFSLSYNYKTGSLEVHIKECRNLAYADEKKKRSNPYVKVYLLPDKSKQSKRKTSVKKNTtNPVFNETLK 72

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 2217396593 533 GILEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKATKHKTLVIKKSVNPQWNHTFMFSGIHPqDIKNVCLELTIWDKE 612
Cdd:cd08384    13 RGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKHS-DLAKKTLEITVWDKD 91

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2217396593 613 AFSSNIFLGGVRLNsgsgvshgknvdwMDSQGEEQRLWQKMANNPGTPFE 662
Cdd:cd08384    92 IGKSNDYIGGLQLG-------------INAKGERLRHWLDCLKNPDKKIE 128

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2217396593 407 SGEILLHISYCYKTGGLYIFVKNCRNLAIGDEKKQRTDAYVKSYLLPDKSRNNKRKTKIRTGT-NPEFNETLK 478
Cdd:cd08393     1 QGSVQFALDYDPKLRELHVHVIQCQDLAAADPKKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTlNPVFNETLR 73

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 2217396593 535 LEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKATKHKTLVIKKSVNPQWNHTFMFSgIHPQDIKNVCLELTIWDKEAF 614
Cdd:cd00276    16 LTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFD-VPAEQLEEVSLVITVVDKDSV 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2217396593 615 SSNIFLGGVRLNSgsgvshgknvdwmDSQGEEQRLWQKMANNPGTP 660
Cdd:cd00276    95 GRNEVIGQVVLGP-------------DSGGEELEHWNEMLASPRKP 127

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2217396593 407 SGEILLHISYCYKTGGLYIFVKNCRNLAIGDEKKQRTDAYVKSYLLPDKSRNNKRKTKIRTGT-NPEFNETLKVEFAPD 484
Cdd:cd08392     1 TGEIEFALHYNFRTSCLEITIKACRNLAYGDEKKKKCHPYVKVCLLPDKSHNSKRKTAVKKGTvNPVFNETLKYVVEAD 79

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 2217396593 533 GILEVFIKEAKNLTAVKSG-GTSDSFVKGYLLPDDSKATKHKTLVIKKSVNPQWNHTFMFSgIHPQDIKNVCLELTIWDK 611
Cdd:cd08521    14 GSLEVHIKECRNLAYADEKkKRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYH-ISKSQLETRTLQLSVWHH 92

                          90       100
                  ....*....|....*....|....*....
gi 2217396593 612 EAFSSNIFLGGVRLNSGSGVSHGKNVDWM 640
Cdd:cd08521    93 DRFGRNTFLGEVEIPLDSWDLDSQQSEWY 121

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2217396593  62 RVCVHCHRNLGLIFDRGDPCQACSLRVCRECRVAGPN-GSWKCTVCDK 108
Cdd:cd15747     1 RICARCREKLGFIFNRGARCPKCSHKVCKKCRVLTSNtGKWLCTVCHK 48

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 2217396593 535 LEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDdskaTKHKTLVIKKSVNPQWNHTFMFsgiHPQDIKNVCLELTIWDKEAF 614
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGK----QKFKTKVVKNTLNPVWNETFEF---PVLDPESDTLTVEVWDKDRF 73

                          90       100
                  ....*....|....*....|....
gi 2217396593 615 SSNIFLGGVRLNSGSGVSHGKNVD 638
Cdd:cd00030    74 SKDDFLGEVEIPLSELLDSGKEGE 97

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 2217396593 531 SGGILEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKATKHKTLVIKKSVNPQWNHTFMFSgIHPQDIKNVCLELTIWD 610
Cdd:cd08405    13 TANRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFN-IPLERLRETTLIITVMD 91

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2217396593 611 KEAFSSNIFLGGVRLNsgsgvshgknvdWMDSQGEEQRlWQKMANNPGTP 660
Cdd:cd08405    92 KDRLSRNDLIGKIYLG------------WKSGGLELKH-WKDMLSKPRQP 128

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 2217396593 535 LEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKATKHKTLVIKKSVNPQWNHTFMFSGIHPQDIKNVCLELTIWDKEAF 614
Cdd:cd04035    17 LHCTIIRAKGLKAMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYGITEEDIQRKTLRLLVLDEDRF 96

                          90
                  ....*....|..
gi 2217396593 615 SSNiFLGGVRLN 626
Cdd:cd04035    97 GND-FLGETRIP 107

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 2217396593 535 LEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKATKHKTLVIKKSVNPQWNHTFMFSgIHPQDIKNVCLELTIWDKEAF 614
Cdd:cd04030    18 LIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFP-VSLEELKRRTLDVAVKNSKSF 96

                          90
                  ....*....|....
gi 2217396593 615 SS--NIFLGGVRLN 626
Cdd:cd04030    97 LSreKKLLGQVLID 110

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217396593 535 LEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDdsKATKHKTLVIKKSVNPQWNHTFMFSGIHPQDIKNVCLELTIWDKEAF 614
Cdd:cd08386    18 LTLKILKAVELPAKDFSGTSDPFVKIYLLPD--KKHKLETKVKRKNLNPHWNETFLFEGFPYEKLQQRVLYLQVLDYDRF 95

                          90
                  ....*....|.
gi 2217396593 615 SSNIFLGGVRL 625
Cdd:cd08386    96 SRNDPIGEVSL 106

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2217396593 408 GEILLHISYCYKTGGLYIFVKNCRNLAIGDEKKQrTDAYVKSYLLPDKSRNNKRKTKIRTGT-NPEFNETLkvEF 481
Cdd:cd04030     3 GRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDI-PDPYVRLYLLPDKSKSTRRKTSVKKDNlNPVFDETF--EF 74

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2217396593 410 ILLHISYCYKTGGLYIFVKNCRNLAIGDEKKQrTDAYVKSYLLPDKSRNNKRKTKIRTGT-NPEFNETLKVEFAPD 484
Cdd:cd08384     2 ILVSLMYNTQRRGLIVGIIRCVNLAAMDANGY-SDPFVKLYLKPDAGKKSKHKTQVKKKTlNPEFNEEFFYDIKHS 76

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 2217396593 535 LEVFIKEAKNLTAvKSGGTSDSFVKGYLLPDDSKATKhKTLVIKKSVNPQWNHTFMF-----SGIHPQ-------DIKNV 602
Cdd:cd08675     1 LSVRVLECRDLAL-KSNGTCDPFARVTLNYSSKTDTK-RTKVKKKTNNPRFDEAFYFeltigFSYEKKsfkveeeDLEKS 78

                          90       100
                  ....*....|....*....|...
gi 2217396593 603 CLELTIWDKEAFSSNIFLGGVRL 625
Cdd:cd08675    79 ELRVELWHASMVSGDDFLGEVRI 101

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
                  ....*....|....*....|....*....|....*....|....*..
gi 2217396593  62 RVCVHCHRNLGLIFDRGDPCQACSLRVCRECRVAGPNGSWKCTVCDK 108
Cdd:cd15764     4 RSCGRCQESLGRLSPKANQCRGCNHLVCRDCRAVRPNGSWVCSVCAK 50

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 2217396593 408 GEILLHISYCYKTGGLYIFVKNCRNLAIGDEKKQrTDAYVKSYLLPDKSRNNKRKTKIRTGT-NPEFNETLKVEFAPDIG 486
Cdd:cd00276     1 GELLLSLSYLPTAERLTVVVLKARNLPPSDGKGL-SDPYVKVSLLQGGKKLKKKKTSVKKGTlNPVFNEAFSFDVPAEQL 79

                          90
                  ....*....|
gi 2217396593 487 LQYKGELTVV 496
Cdd:cd00276    80 EEVSLVITVV 89

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2217396593 408 GEILLHISYcyKTGGLYIFVKNCRNLAIGDEKKQrTDAYVKSYLLPDKSRNNKRKTKIRTGT-NPEFNETL 477
Cdd:cd04026     2 GRIYLKISV--KDNKLTVEVREAKNLIPMDPNGL-SDPYVKLKLIPDPKNETKQKTKTIKKTlNPVWNETF 69

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 2217396593 535 LEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKATKHKTLVIKKSVNPQWNHTFMFSgIHPQDIKNVCLELTIWDKEAF 614
Cdd:cd08406    17 LTVVVVKARNLVWDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFS-VPAIVLQDLSLRVTVAESTED 95

                          90       100
                  ....*....|....*....|..
gi 2217396593 615 SSNIFLGGVRLN---SGSGVSH 633
Cdd:cd08406    96 GKTPNVGHVIIGpaaSGMGLSH 117

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217396593 531 SGGILEVFIKEAKNLTAVKSGGTSDSFVKGYLLPDDSKATKHKTLVIKKSVNPQWNHTFMFSgIHPQDIKNVCLELTIWD 610
Cdd:cd08410    12 SAGRLNVDIIRAKQLLQTDMSQGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFK-VPQEELENVSLVFTVYG 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2217396593 611 KEAFSSNIFLGGVRLNSGSgvshgknvdwmdSQGEEQRLWQKMANNPGTPFE 662
Cdd:cd08410    91 HNVKSSNDFIGRIVIGQYS------------SGPSETNHWRRMLNSQRTAVE 130