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 2074014167 1342 LGPAQLVGRQTLATPAMGDIQVGMMDKKGQLEVEIIRARGLVVKPGSKTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEP 1421
Cdd:cd04028      1 LGPGQLVGRQVLASPSMGDIQLGLYDKKGQLEVEVIRARGLVQKPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDP 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2074014167 1422 LYQQLLSFEESPQGKVLQIIVWGDYGRMDHKSFMGVAQILLDELELSNMVIGWFKLFPPSSLVDPT 1487
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 2074014167  620 DRLIGRILLNKRLKDGSvprDSGAMLGLKVVGGKMTESGRLCAFITKVKKGSLADTVGHLRPGDEVLEWNGRLLQGATFE 699
Cdd:cd06714      1 DFLIGRIILQRDPKDGS---VSGNGLGLKVVGGKMTESGRLGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFE 77

                           90       100
                   ....*....|....*....|
gi 2074014167  700 EVYNIILESKpePQVELVVS 719
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 2074014167 1342 LGPAQLVGRQTLATPAMGDIQVGMMDKKGQLEVEIIRARGLVVKPGSKTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEP 1421
Cdd:cd04028      1 LGPGQLVGRQVLASPSMGDIQLGLYDKKGQLEVEVIRARGLVQKPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDP 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2074014167 1422 LYQQLLSFEESPQGKVLQIIVWGDYGRMDHKSFMGVAQILLDELELSNMVIGWFKLFPPSSLVDPT 1487
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 2074014167  620 DRLIGRILLNKRLKDGSvprDSGAMLGLKVVGGKMTESGRLCAFITKVKKGSLADTVGHLRPGDEVLEWNGRLLQGATFE 699
Cdd:cd06714      1 DFLIGRIILQRDPKDGS---VSGNGLGLKVVGGKMTESGRLGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFE 77

                           90       100
                   ....*....|....*....|
gi 2074014167  700 EVYNIILESKpePQVELVVS 719
Cdd:cd06714     78 EVQDIISQSK--GEVELVVS 95

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2074014167 1370 GQLEVEIIRARGLVVKPGSKTlPAPYVKVYLLDNGVciaKKKTKVARKTLEPLYQQLLSFE-ESPQGKVLQIIVWgDYGR 1448
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGT-SDPYVKVYLLDGKQ---KKKTKVVKNTLNPVWNETFTFSvPDPENAVLEIEVY-DYDR 75

                           90       100
                   ....*....|....*....|....*....
gi 2074014167 1449 MDHKSFMGVAQILLDELELSNMVIGWFKL 1477
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 2074014167  1371 QLEVEIIRARGLVVKPGSKTlPAPYVKVYLldNGVCIAKKKTKVARKTLEPLYQQLLSFE-ESPQGKVLQIIVWgDYGRM 1449
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGK-SDPYVKVSL--DGDPKEKKKTKVVKNTLNPVWNETFEFEvPPPELAELEIEVY-DKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 2074014167  1450 DHKSFMGVAQILLDELELSNMVIGW 1474
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 2074014167   30 SHLTEEERKIILAVMDR----QKKEEEK-EQSVLKVKEEhkpqltqwfpfsgitELVNNVLQPQQkQQNEKepqtklhqq 104
Cdd:pfam02318    1 SKLTDEEAEHVWEVVQRdfdlRKKEEERlGELKGKLDKE---------------SSKRELLGNQA-HLGET--------- 55

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2074014167  105 femykeqvkkmgeesqqqqeqkgdapTCGICH-KTKFADGCGHNCSYCQTKFCARCGgrvslRSNKEDKVvmWVCNLCRK 183
Cdd:pfam02318   56 --------------------------HCIRCLqPFGFLVNSKRQCLDCRKNVCKKCG-----VYNKPEQG--WLCDPCSE 102

                          170
                   ....*....|....*
gi 2074014167  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 2074014167  636 SVPRDSGAMLGLKVVGGkmtesgrlcAFITKVKKGSLADTVGhLRPGDEVLEWNGRLLqgATFEEVYNIILESKPEPQVE 715
Cdd:COG0265    186 PVTPELAEALGLPEPEG---------VLVARVEPGSPAAKAG-LRPGDVILAVDGKPV--TSARDLQRLLASLKPGDTVT 253

                   ....*
gi 2074014167  716 LVVSR 720
Cdd:COG0265    254 LTVLR 258

PDZ domain; PDZ domains are found in diverse signaling proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2074014167  636 SVPRDSGAMLGLKVVGGkmTESGRLCAFITKVKKGSLADTVGhLRPGDEVLEWNGRLLQGATFEEVYNIILESKPEpqVE 715
Cdd:pfam00595    3 TLEKDGRGGLGFSLKGG--SDQGDPGIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGK--VT 77

                   ...
gi 2074014167  716 LVV 718
Cdd:pfam00595   78 LTI 80

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 2074014167 1342 LGPAQLVGRQTLATPAMGDIQVGMMDKKGQLEVEIIRARGLVVKPGSKTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEP 1421
Cdd:cd04028      1 LGPGQLVGRQVLASPSMGDIQLGLYDKKGQLEVEVIRARGLVQKPGSKVLPAPYVKVYLLEGKKCIAKKKTKIARKTLDP 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2074014167 1422 LYQQLLSFEESPQGKVLQIIVWGDYGRMDHKSFMGVAQILLDELELSNMVIGWFKLFPPSSLVDPT 1487
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 2074014167  620 DRLIGRILLNKRLKDGSvprDSGAMLGLKVVGGKMTESGRLCAFITKVKKGSLADTVGHLRPGDEVLEWNGRLLQGATFE 699
Cdd:cd06714      1 DFLIGRIILQRDPKDGS---VSGNGLGLKVVGGKMTESGRLGAYVTKVKPGSVADTVGHLREGDEVLEWNGISLQGKTFE 77

                           90       100
                   ....*....|....*....|
gi 2074014167  700 EVYNIILESKpePQVELVVS 719
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 2074014167  773 GQLSIKLWFDKVGHQLIVTILGAKDLPSREDGRPRNPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYsPVHRREF 852
Cdd:cd04030      3 GRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEF-PVSLEEL 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 2074014167  853 RERMLEITLWDQARVREEESEFLGEILIELETALLDD-EPHWYKLQ 897
Cdd:cd04030     82 KRRTLDVAVKNSKSFLSREKKLLGQVLIDLSDLDLSKgFTQWYDLT 127

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 2074014167  764 LRDVPQFLSGQLSIKLwfdKVGHQLIVTILGAKDLPSREDGRPRNPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFI 843
Cdd:cd04020      8 LKYVPPESEGALKSKK---PSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNHTFV 84

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2074014167  844 YSPVHRREFRERMLEITLWDQARVreEESEFLG 876
Cdd:cd04020     85 YDGVSPEDLSQACLELTVWDHDKL--SSNDFLG 115

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 2074014167  788 LIVTILGAKDLPSrEDGRPRNPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYSPVHRREFRERMLEITLWDQARV 867
Cdd:cd08381     15 LFVMVMHAKNLPL-LDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQQRVLQVSVWSHDSL 93

                           90       100       110
                   ....*....|....*....|....*....|
gi 2074014167  868 ReeESEFLGEILIELETALLDDE-PHWYKL 896
Cdd:cd08381     94 V--ENEFLGGVCIPLKKLDLSQEtEKWYPL 121

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 2074014167  788 LIVTILGAKDLPSREDGRPRNPYVKIYFLpdrsDKNKRRTKTVKKTLEPKWNQTFIYspvHRREFRERMLEITLWDQARV 867
Cdd:cd00030      1 LRVTVIEARNLPAKDLNGKSDPYVKVSLG----GKQKFKTKVVKNTLNPVWNETFEF---PVLDPESDTLTVEVWDKDRF 73

                           90       100       110
                   ....*....|....*....|....*....|.
gi 2074014167  868 REEesEFLGEILIELETALLDDEPH--WYKL 896
Cdd:cd00030     74 SKD--DFLGEVEIPLSELLDSGKEGelWLPL 102

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2074014167  778 KLWF----DKVGHQLIVTILGAKDLPSR-EDGRPRNPYVKIYFLPDrsDKNKRRTKTVKKTLEPKWNQTFIYsPVHRREF 852
Cdd:cd08390      2 RLWFsvqyDLEEEQLTVSLIKARNLPPRtKDVAHCDPFVKVCLLPD--ERRSLQSKVKRKTQNPNFDETFVF-QVSFKEL 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2074014167  853 RERMLEITLWDQARVREEESefLGEILIELETALLDDEPHWYK 895
Cdd:cd08390     79 QRRTLRLSVYDVDRFSRHCI--IGHVLFPLKDLDLVKGGVVWR 119

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 2074014167  772 SGQLSIKLWFDKVGHQLIVTILGAKDLPSREDGRPR-NPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYSpVHRR 850
Cdd:cd08393      1 QGSVQFALDYDPKLRELHVHVIQCQDLAAADPKKQRsDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYK-VERE 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 2074014167  851 EFRERMLEITLWDQARVReeESEFLGEILIELETALLDD-EPHWYKLQ 897
Cdd:cd08393     80 ELPTRVLNLSVWHRDSLG--RNSFLGEVEVDLGSWDWSNtQPTWYPLQ 125

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains 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 2074014167  637 VPRDSGAMLGLKVVGGKMTESGrlcAFITKVKKGSLADTVGHLRPGDEVLEWNGRLLQGATFEEVYNIILESKPEpqVEL 716
Cdd:cd00136      4 LEKDPGGGLGFSIRGGKDGGGG---IFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGE--VTL 78

                   ..
gi 2074014167  717 VV 718
Cdd:cd00136     79 TV 80

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 2074014167  1371 QLEVEIIRARGLVVKPGSKTlPAPYVKVYLldNGVCIAKKKTKVARKTLEPLYQQLLSFE-ESPQGKVLQIIVWgDYGRM 1449
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGK-SDPYVKVSL--DGDPKEKKKTKVVKNTLNPVWNETFEFEvPPPELAELEIEVY-DKDRF 76

                            90       100
                    ....*....|....*....|....*
gi 2074014167  1450 DHKSFMGVAQILLDELELSNMVIGW 1474
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 2074014167  773 GQLSIKLWFDKVGHQLIVTILGAKDLPSREDGRPRNPYVKIYFLPDRsdKNKRRTKTVKKTLEPKWNQTFIYSPVHRREF 852
Cdd:cd08386      3 GRIQFSVSYDFQESTLTLKILKAVELPAKDFSGTSDPFVKIYLLPDK--KHKLETKVKRKNLNPHWNETFLFEGFPYEKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 2074014167  853 RERMLEITLWDQARVREEESefLGEILIELETALLDDEPHWYK 895
Cdd:cd08386     81 QQRVLYLQVLDYDRFSRNDP--IGEVSLPLNKVDLTEEQTFWK 121

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2074014167  773 GQLSIKLWFDKVGHQLIVTILGAKDLPSREDGRPRNPYVKIYFLPDRsdKNKRRTKTVKKTLEPKWNQTFIYsPVHRREF 852
Cdd:cd08385      3 GKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDK--KKKFETKVHRKTLNPVFNETFTF-KVPYSEL 79

                           90
                   ....*....|.
gi 2074014167  853 RERMLEITLWD 863
Cdd:cd08385     80 GNKTLVFSVYD 90

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 2074014167  787 QLIVTILGAKDLPSREDGRPRNPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYSPVHrREFRERMLEITLWDQAR 866
Cdd:cd08384     14 GLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYDIKH-SDLAKKTLEITVWDKDI 92

                           90       100
                   ....*....|....*....|....*....
gi 2074014167  867 VReeESEFLGEILIELeTALLDDEPHWYK 895
Cdd:cd08384     93 GK--SNDYIGGLQLGI-NAKGERLRHWLD 118

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2074014167 1359 GDIQVGM--MDKKGQLEVEIIRARGLVvKPGSKTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEPLYQQLLSFE---ESP 1433
Cdd:cd00276      1 GELLLSLsyLPTAERLTVVVLKARNLP-PSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDvpaEQL 79

                           90       100
                   ....*....|....*....|...
gi 2074014167 1434 QGKVLQIIVWgDYGRMDHKSFMG 1456
Cdd:cd00276     80 EEVSLVITVV-DKDSVGRNEVIG 101

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2074014167   631 RLKDGSVPRDSGaMLGLKVVGGKMTESGrlcAFITKVKKGSLADTVGhLRPGDEVLEWNGRLLQGATFEEVYNIILESKP 710
Cdd:smart00228    1 EPRLVELEKGGG-GLGFSLVGGKDEGGG---VVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKAGG 75

                            90
                    ....*....|.
gi 2074014167   711 EpqVELVVSRP 721
Cdd:smart00228   76 K--VTLTVLRG 84

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2074014167 1368 KKGQLEVEIIRARGLVVKPGSKTLPAPYVKVYLLDNGVCIAKKKTKVARKTLEPLYQQLLSFEESP---QGKVLQIIVWg 1444
Cdd:cd04029     13 KTQSLNVHVKECRNLAYGDEAKKRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSISHsqlETRTLQLSVW- 91

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2074014167 1445 DYGRMDHKSFMGVAQILLDELELSNMVIGWFKL 1477
Cdd:cd04029     92 HYDRFGRNTFLGEVEIPLDSWNFDSQHEECLPL 124

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 2074014167 1372 LEVEIIRARGLVVKPGSKtLPAPYVKVYLLDNGVCIAKKKTKVARKTLEPLYQQ----LLSFEESPQgKVLQIIVWGDYG 1447
Cdd:cd04030     18 LIVTVHKCRNLPPCDSSD-IPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDEtfefPVSLEELKR-RTLDVAVKNSKS 95

                           90       100       110
                   ....*....|....*....|....*....|.
gi 2074014167 1448 RMD-HKSFMGVAQILLDELELSNMVIGWFKL 1477
Cdd:cd04030     96 FLSrEKKLLGQVLIDLSDLDLSKGFTQWYDL 126

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 2074014167  645 LGLKVVGGKMTESGRLCAFITKVKKGSLADTVGHLRPGDEVLEWNGRLLQGATFEEVYNiILESKPEPqVELVVSRP 721
Cdd:cd06758     14 LGIQITGGKGSKRGDIGIFVAGVEEGGSADRDGRLKKGDELLMINGQSLIGLSHQEAVA-ILRSSASP-VQLVIASK 88