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 767953863 1541 LGPAQLVGRQTLATPAMGDIQVGMMDKKGQLEVEIIRARGLVVKPGSKTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEP 1620
Cdd:cd04028     1 LGPGQLVGRQVLASPSMGDIQLGLYDKKGQLEVEVIRARGLVQKPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDP 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767953863 1621 LYQQLLSFEESPQGKVLQIIVWGDYGRMDHKSFMGVAQILLDELELSNMVIGWFKLFPPSSLVDPT 1686
Cdd:cd04028    81 LYQQQLVFDVSPTGKTLQVIVWGDYGRMDKKVFMGVAQILLDDLDLSNLVIGWYKLFPTSSLVDPT 146

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863  681 DRLIGRILLNKRLKDGSvprDSGAMLGLKVVGGKMTESGRLCAFITKVKKGSLADTVGHLRPGDEVLEWNGRLLQGATFE 760
Cdd:cd06714     1 DFLIGRIILQRDPKDGS---VSGNGLGLKVVGGKMTESGRLGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFE 77

                          90       100
                  ....*....|....*....|
gi 767953863  761 EVYNIILESKpePQVELVVS 780
Cdd:cd06714    78 EVQDIISQSK--GEVELVVS 95

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 767953863 1541 LGPAQLVGRQTLATPAMGDIQVGMMDKKGQLEVEIIRARGLVVKPGSKTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEP 1620
Cdd:cd04028     1 LGPGQLVGRQVLASPSMGDIQLGLYDKKGQLEVEVIRARGLVQKPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDP 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767953863 1621 LYQQLLSFEESPQGKVLQIIVWGDYGRMDHKSFMGVAQILLDELELSNMVIGWFKLFPPSSLVDPT 1686
Cdd:cd04028    81 LYQQQLVFDVSPTGKTLQVIVWGDYGRMDKKVFMGVAQILLDDLDLSNLVIGWYKLFPTSSLVDPT 146

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863  681 DRLIGRILLNKRLKDGSvprDSGAMLGLKVVGGKMTESGRLCAFITKVKKGSLADTVGHLRPGDEVLEWNGRLLQGATFE 760
Cdd:cd06714     1 DFLIGRIILQRDPKDGS---VSGNGLGLKVVGGKMTESGRLGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFE 77

                          90       100
                  ....*....|....*....|
gi 767953863  761 EVYNIILESKpePQVELVVS 780
Cdd:cd06714    78 EVQDIISQSK--GEVELVVS 95

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863  1569 GQLEVEIIRARGLVVKPGSKTlPAPYVKVYLLDNGVciaKKKTKVARKTLEPLYQQLLSFE-ESPQGKVLQIIVWgDYGR 1647
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGT-SDPYVKVYLLDGKQ---KKKTKVVKNTLNPVWNETFTFSvPDPENAVLEIEVY-DYDR 75

                           90       100
                   ....*....|....*....|....*....
gi 767953863  1648 MDHKSFMGVAQILLDELELSNMVIGWFKL 1676
Cdd:pfam00168   76 FGRDDFIGEVRIPLSELDSGEGLDGWYPL 104

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 767953863   1570 QLEVEIIRARGLVVKPGSKTlPAPYVKVYLldNGVCIAKKKTKVARKTLEPLYQQLLSFE-ESPQGKVLQIIVWgDYGRM 1648
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGK-SDPYVKVSL--DGDPKEKKKTKVVKNTLNPVWNETFEFEvPPPELAELEIEVY-DKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 767953863   1649 DHKSFMGVAQILLDELELSNMVIGW 1673
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

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 767953863    30 SHLTEEERKIILAVMDR----QKKEEEK-EQSVLKVKEEhkpqltqwfpfsgitELVNNVLQPQQkQQNEKepqtklhqq 104
Cdd:pfam02318    1 SKLTDEEAEHVWEVVQRdfdlRKKEEERlGELKGKLDKE---------------SSKRELLGNQA-HLGET--------- 55

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863   105 femykeqvkkmgeesqqqqeqkgdapTCGICH-KTKFADGCGHNCSYCQTKFCARCGgrvslRSNKEDKVvmWVCNLCRK 183
Cdd:pfam02318   56 --------------------------HCIRCLqPFGFLVNSKRQCLDCRKNVCKKCG-----VYNKPEQG--WLCDPCSE 102

                          170
                   ....*....|....*
gi 767953863   184 QQEILTKSGAWFYNS 198
Cdd:pfam02318  103 ARELKKGSLEWFYKN 117

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863  697 SVPRDSGAMLGLKVVGGkmtesgrlcAFITKVKKGSLADTVGhLRPGDEVLEWNGRLLqgATFEEVYNIILESKPEPQVE 776
Cdd:COG0265   186 PVTPELAEALGLPEPEG---------VLVARVEPGSPAAKAG-LRPGDVILAVDGKPV--TSARDLQRLLASLKPGDTVT 253

                  ....*
gi 767953863  777 LVVSR 781
Cdd:COG0265   254 LTVLR 258

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863  865 LIVTILGAKDLpSREDGRPRN---PYVKIYFlpdrSDKNKRRTKTVKKTLEPKWNQTFiYSPVHRreFRERmLEITLWDQ 941
Cdd:COG5038   438 VEVKIKSAEGL-KKSDSTINGtvdPYITVTF----SDRVIGKTRVKKNTLNPVWNETF-YILLNS--FTDP-LNLSLYDF 508

                          90       100
                  ....*....|....*....|....*..
gi 767953863  942 ARVREEesEFLGEILIELetALLDDEP 968
Cdd:COG5038   509 NSFKSD--KVVGSTQLDL--ALLHQNP 531

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 767953863 1541 LGPAQLVGRQTLATPAMGDIQVGMMDKKGQLEVEIIRARGLVVKPGSKTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEP 1620
Cdd:cd04028     1 LGPGQLVGRQVLASPSMGDIQLGLYDKKGQLEVEVIRARGLVQKPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDP 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767953863 1621 LYQQLLSFEESPQGKVLQIIVWGDYGRMDHKSFMGVAQILLDELELSNMVIGWFKLFPPSSLVDPT 1686
Cdd:cd04028    81 LYQQQLVFDVSPTGKTLQVIVWGDYGRMDKKVFMGVAQILLDDLDLSNLVIGWYKLFPTSSLVDPT 146

PDZ domain of Rab3-interacting molecule 1 (RIM), RIM2, piccolo and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RIM, RIM2, piccolo and related domains. RIM proteins and Gallus gallus protein piccolo (also called aczonin) are involved in neurotransmitter release at presynaptic active zones, the site of vesicle fusion. A protein complex containing RIM proteins positions synaptic vesicles containing synaptotagmin at the active zone. RIM proteins simultaneously activate docking and priming of synaptic vesicles and recruit Ca2+-channels to active zones, thereby connecting primed synaptic vesicles to Ca2+-channels. RIM binding to vesicular Rab proteins (Rab3 and Rab27 isoforms) mediates vesicle docking; RIM binding to Munc13 activates vesicle priming; RIM binding to the Ca2+-channel, both directly and indirectly via RIM-BP, recruits the Ca2+-channels. The RIM PDZ domain interacts with the C-termini of N- and P/Q-type voltage-gated Ca2+-channels. RIM1, RIM2 and piccolo also participate in regulated exocytosis through binding cAMP-GEFII (cAMP-binding protein-guanidine nucleotide exchange factor II). The piccolo PDZ domain binds cAMP-GEFII. RIM2 also plays a role in dendrite formation by melanocytes. Caenorhabditis elegans RIM (also known as unc-10) may be involved in the regulation of defecation and daumone response. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RIM-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863  681 DRLIGRILLNKRLKDGSvprDSGAMLGLKVVGGKMTESGRLCAFITKVKKGSLADTVGHLRPGDEVLEWNGRLLQGATFE 760
Cdd:cd06714     1 DFLIGRIILQRDPKDGS---VSGNGLGLKVVGGKMTESGRLGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFE 77

                          90       100
                  ....*....|....*....|
gi 767953863  761 EVYNIILESKpePQVELVVS 780
Cdd:cd06714    78 EVQDIISQSK--GEVELVVS 95

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 767953863  851 RVQIKLWFDKVGHQLIVTILGAKDLPSREDGRPRNPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYsPVHRREFR 930
Cdd:cd04030     4 RIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEF-PVSLEELK 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 767953863  931 ERMLEITLWDQARVREEESEFLGEILIELETALLDD-EPHWYKLQ 974
Cdd:cd04030    83 RRTLDVAVKNSKSFLSREKKLLGQVLIDLSDLDLSKgFTQWYDLT 127

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863  850 PRVQIKLWFDKVGhqLIVTILGAKDLPSrEDGRPRNPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYSPVHRREF 929
Cdd:cd08381     2 GQVKLSISYKNGT--LFVMVMHAKNLPL-LDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDL 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 767953863  930 RERMLEITLWDQARVReeESEFLGEILIELETALLDDE-PHWYKL 973
Cdd:cd08381    79 QQRVLQVSVWSHDSLV--ENEFLGGVCIPLKKLDLSQEtEKWYPL 121

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 767953863    864 QLIVTILGAKDLPSREDGRPRNPYVKIYFLPDRsdKNKRRTKTVKKTLEPKWNQTFIYsPVHRREfrERMLEITLWDQAR 943
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDP--KEKKKTKVVKNTLNPVWNETFEF-EVPPPE--LAELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*...
gi 767953863    944 VREEesEFLGEILIELETALLDDEPHWY 971
Cdd:smart00239   76 FGRD--DFIGQVTIPLSDLLLGGRHEKL 101

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 767953863  865 LIVTILGAKDLPSREDGRPRNPYVKIYFLpdrsDKNKRRTKTVKKTLEPKWNQTFIYspvHRREFRERMLEITLWDQARV 944
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLG----GKQKFKTKVVKNTLNPVWNETFEF---PVLDPESDTLTVEVWDKDRF 73

                          90       100       110
                  ....*....|....*....|....*....|.
gi 767953863  945 REEesEFLGEILIELETALLDDEPH--WYKL 973
Cdd:cd00030    74 SKD--DFLGEVEIPLSELLDSGKEGelWLPL 102

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 767953863  851 RVQIKLWFDKVGHQLIVTILGAKDLPSREDGRPR-NPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYSpVHRREF 929
Cdd:cd08393     3 SVQFALDYDPKLRELHVHVIQCQDLAAADPKKQRsDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYK-VEREEL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 767953863  930 RERMLEITLWDQARVReeESEFLGEILIELETALLDD-EPHWYKLQ 974
Cdd:cd08393    82 PTRVLNLSVWHRDSLG--RNSFLGEVEVDLGSWDWSNtQPTWYPLQ 125

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863 1558 GDIQVGMMDKKGQLEVEIIRARGLVVKPGSKtlPAPYVKVYLLDNGVCIAKKKTKVARKTLEPLYQQLLSFEESP----Q 1633
Cdd:cd08381     2 GQVKLSISYKNGTLFVMVMHAKNLPLLDGSD--PDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPvedlQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 767953863 1634 GKVLQIIVWGDyGRMDHKSFMGVAQILLDELELSNMVIGWFKL 1676
Cdd:cd08381    80 QRVLQVSVWSH-DSLVENEFLGGVCIPLKKLDLSQETEKWYPL 121

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 767953863 1558 GDIQVGMM--DKKGQLEVEIIRARGLVVKPGSKTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEPLYQQLLSF---EESP 1632
Cdd:cd08521     1 GEIEFSLSynYKTGSLEVHIKECRNLAYADEKKKRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYhisKSQL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 767953863 1633 QGKVLQIIVWgDYGRMDHKSFMGVAQILLDELELSNMVIGWFKL 1676
Cdd:cd08521    81 ETRTLQLSVW-HHDRFGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123

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 767953863   1570 QLEVEIIRARGLVVKPGSKTlPAPYVKVYLldNGVCIAKKKTKVARKTLEPLYQQLLSFE-ESPQGKVLQIIVWgDYGRM 1648
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGK-SDPYVKVSL--DGDPKEKKKTKVVKNTLNPVWNETFEFEvPPPELAELEIEVY-DKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 767953863   1649 DHKSFMGVAQILLDELELSNMVIGW 1673
Cdd:smart00239   77 GRDDFIGQVTIPLSDLLLGGRHEKL 101

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 767953863  848 FVPRVQIKLWFDKVGHQLIVTILGAKDLPSREDGRPRNPYVKIYFLPDRsdKNKRRTKTVKKTLEPKWNQTFIYSPVHRR 927
Cdd:cd08386     1 NLGRIQFSVSYDFQESTLTLKILKAVELPAKDFSGTSDPFVKIYLLPDK--KHKLETKVKRKNLNPHWNETFLFEGFPYE 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 767953863  928 EFRERMLEITLWDQARVREEESefLGEILIELETALLDDEPHWYK 972
Cdd:cd08386    79 KLQQRVLYLQVLDYDRFSRNDP--IGEVSLPLNKVDLTEEQTFWK 121

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863 1560 IQVGMMDKKGQLEVEIIRARGLVVKPGSkTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEPLYQQLLSFEESPQ----GK 1635
Cdd:cd04031     7 IQLWYDKVTSQLIVTVLQARDLPPRDDG-SLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRetlkER 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 767953863 1636 VLQIIVWgDYGRMDHKSFMGVAQILLDELELSNMVIgWFKL 1676
Cdd:cd04031    86 TLEVTVW-DYDRDGENDFLGEVVIDLADALLDDEPH-WYPL 124

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863 1558 GDIQVGMM--DKKGQLEVEIIRARGLVVKPGSKTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEPLYQQLLSFE---ESP 1632
Cdd:cd08393     2 GSVQFALDydPKLRELHVHVIQCQDLAAADPKKQRSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKverEEL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 767953863 1633 QGKVLQIIVWgDYGRMDHKSFMGVAQILLDELELSNMVIGWFKL 1676
Cdd:cd08393    82 PTRVLNLSVW-HRDSLGRNSFLGEVEVDLGSWDWSNTQPTWYPL 124

C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863  852 VQIKLWFDKVGHQLIVTILGAKDLPSREDGRPR-NPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYsPVHRREFR 930
Cdd:cd08392     4 IEFALHYNFRTSCLEITIKACRNLAYGDEKKKKcHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKY-VVEADLLS 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 767953863  931 ERMLEITLWDQARVREEesEFLGEILIELETALLDDEP----HWYKL 973
Cdd:cd08392    83 SRQLQVSVWHSRTLKRR--VFLGEVLIPLADWDFEDTDsqrfLWYPL 127

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767953863  853 QIKLWFDKVGHQLIVTILGAKDLPSREDGrPRNPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYsPVHRREFRER 932
Cdd:cd08685     2 QLKLSIEGQNRKLTLHVLEAKGLRSTNSG-TCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSF-DVNERDYQKR 79

                          90       100
                  ....*....|....*....|.
gi 767953863  933 MLeITLWDQARvREEESEFLG 953
Cdd:cd08685    80 LL-VTVWNKLS-KSRDSGLLG 98

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 767953863 1558 GDIQVGMMDKKGQLEVEIIRARGLVvkPGSKT-LPAPYVKVYLLDNGVCIAKKKTKVARKTLEPLYQQLLSFEESPQGK- 1635
Cdd:cd04026     2 GRIYLKISVKDNKLTVEVREAKNLI--PMDPNgLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKd 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 767953863 1636 -VLQIIVWgDYGRMDHKSFMGVAQILLDELeLSNMVIGWFKL 1676
Cdd:cd04026    80 rRLSIEVW-DWDRTTRNDFMGSLSFGVSEL-IKMPVDGWYKL 119

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 767953863  850 PRVQIKLWFDKVGHQLIVTILGAKDLPSREDGRPRNPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYsPVHRREF 929
Cdd:cd00276     1 GELLLSLSYLPTAERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSF-DVPAEQL 79

                          90       100
                  ....*....|....*....|....*...
gi 767953863  930 RERMLEITLWDQARVReeESEFLGEILI 957
Cdd:cd00276    80 EEVSLVITVVDKDSVG--RNEVIGQVVL 105

PDZ domain 2 of PDZ domain containing 2 (PDZD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of PDZD2, also known as KIAA0300, PIN-1, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains, and is expressed at exceptionally high levels in the pancreas and certain cancer tissues such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD2-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767953863  706 LGLKVVGGKMTESGRLCAFITKVKKGSLADTVGHLRPGDEVLEWNGRLLQGATFEEVYNiILESKPEPqVELVVSRP 782
Cdd:cd06758    14 LGIQITGGKGSKRGDIGIFVAGVEEGGSADRDGRLKKGDELLMINGQSLIGLSHQEAVA-ILRSSASP-VQLVIASK 88