C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. 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 1958770388    5 LKVKIVAGRHLPVMDRASDLTDAFVEVKFGNTTFKTDVYLKSLNPQWNSEWFKFEvwfqVDDEDLQDEPLQITVLDHDTY 84
Cdd:cd08688      1 LKVRVVAARDLPVMDRSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNSEWFRFE----VDDEELQDEPLQIRVMDHDTY 76

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1958770388   85 SANDAIGKVYIDIDPLLYSEAATVISGWFPIYDT 118
Cdd:cd08688     77 SANDAIGKVYIDLNPLLLKDSVSQISGWFPIYDT 110

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. 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 1958770388    5 LKVKIVAGRHLPVMDRASDLTDAFVEVKFGNTTFKTDVYLKSLNPQWNSEWFKFEvwfqVDDEDLQDEPLQITVLDHDTY 84
Cdd:cd08688      1 LKVRVVAARDLPVMDRSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNSEWFRFE----VDDEELQDEPLQIRVMDHDTY 76

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1958770388   85 SANDAIGKVYIDIDPLLYSEAATVISGWFPIYDT 118
Cdd:cd08688     77 SANDAIGKVYIDLNPLLLKDSVSQISGWFPIYDT 110

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 1958770388     4 KLKVKIVAGRHLPVMDRaSDLTDAFVEVKFGN---TTFKTDVYLKSLNPQWNSEwFKFEVwfqvddEDLQDEPLQITVLD 80
Cdd:smart00239    1 TLTVKIISARNLPPKDK-GGKSDPYVKVSLDGdpkEKKKTKVVKNTLNPVWNET-FEFEV------PPPELAELEIEVYD 72

                            90       100
                    ....*....|....*....|.
gi 1958770388    81 HDTYSANDAIGKVYIDIDPLL 101
Cdd:smart00239   73 KDRFGRDDFIGQVTIPLSDLL 93

Uncharacterized pentameric protein YbjQ, UPF0145 family [Function unknown];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388  461 FVGimGNTRSY-KLLDwnsfnsdepETRDawwaEIRQEIKSHAKALGCHAVVGYS-ESTSICEEVCILSASGTAAVLSPR 538
Cdd:COG0393     39 LVG--GESGAYeELLE---------EARE----EALERMKEEARALGANAVVGVRfDTSEIGGGMLEVLAYGTAVKVEPE 103

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. 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 1958770388    5 LKVKIVAGRHLPVMDRASDLTDAFVEVKFGNTTFKTDVYLKSLNPQWNSEWFKFEvwfqVDDEDLQDEPLQITVLDHDTY 84
Cdd:cd08688      1 LKVRVVAARDLPVMDRSSDLTDAFVEVKFGSTTYKTDVVKKSLNPVWNSEWFRFE----VDDEELQDEPLQIRVMDHDTY 76

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1958770388   85 SANDAIGKVYIDIDPLLYSEAATVISGWFPIYDT 118
Cdd:cd08688     77 SANDAIGKVYIDLNPLLLKDSVSQISGWFPIYDT 110

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 1958770388    5 LKVKIVAGRHLPVMDRaSDLTDAFVEVKFGNT-TFKTDVYLKSLNPQWNsEWFKFEVwfqvddEDLQDEPLQITVLDHDT 83
Cdd:cd00030      1 LRVTVIEARNLPAKDL-NGKSDPYVKVSLGGKqKFKTKVVKNTLNPVWN-ETFEFPV------LDPESDTLTVEVWDKDR 72

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1958770388   84 YSANDAIGKVYIDIDPLLYSEaaTVISGWFPI 115
Cdd:cd00030     73 FSKDDFLGEVEIPLSELLDSG--KEGELWLPL 102

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (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 1958770388    2 PGKLKVKIVAGRHLPVMDRASdlTDAFVEVKFGNTTFKTDVYLKSLNPQWNSEwfkfeVWFQVDDEDLqdePLQITVLDH 81
Cdd:cd04038      1 LGLLKVRVVRGTNLAVRDFTS--SDPYVVLTLGNQKVKTRVIKKNLNPVWNEE-----LTLSVPNPMA---PLKLEVFDK 70

                           90       100
                   ....*....|....*....|....*
gi 1958770388   82 DTYSANDAIGKVYIDIDPLLysEAA 106
Cdd:cd04038     71 DTFSKDDSMGEAEIDLEPLV--EAA 93

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    4 KLKVKIVAGRHLPVMDRaSDLTDAFVEVKFGNTTFKTDVYLKSLNPQWNsEWFKFEVwfqvddEDLQDEPLQITVLDHDT 83
Cdd:cd04025      1 RLRCHVLEARDLAPKDR-NGTSDPFVRVFYNGQTLETSVVKKSCYPRWN-EVFEFEL------MEGADSPLSVEVWDWDL 72

                           90       100       110
                   ....*....|....*....|....*....|
gi 1958770388   84 YSANDAIGKVYIDIDPLLYSEAATvisGWF 113
Cdd:cd04025     73 VSKNDFLGKVVFSIQTLQQAKQEE---GWF 99

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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-II topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388   10 VAGRHLPVMDrASDLTDAFVEVKFGNTTFKTDVYLKSLNPQWnSEWFKFEVWfqvDDedlQDEPLQITVLDHDTYSANDA 89
Cdd:cd08376      7 VEGKNLPPMD-DNGLSDPYVKFRLGNEKYKSKVCSKTLNPQW-LEQFDLHLF---DD---QSQILEIEVWDKDTGKKDEF 78

                           90
                   ....*....|.
gi 1958770388   90 IGKVYIDIDPL 100
Cdd:cd08376     79 IGRCEIDLSAL 89

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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 fifth C2 repeat, C2E, and has a type-II topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    5 LKVKIVAGRHLPVMDRaSDLTDAFVEVKF-GNTTFKTDVYLKSLNPQWNsEWFKFEVWFQVDDEdlqdepLQITVLDHDT 83
Cdd:cd04040      1 LTVDVISAENLPSADR-NGKSDPFVKFYLnGEKVFKTKTIKKTLNPVWN-ESFEVPVPSRVRAV------LKVEVYDWDR 72

                           90
                   ....*....|....*....
gi 1958770388   84 YSANDAIGKVYID---IDP 99
Cdd:cd04040     73 GGKDDLLGSAYIDlsdLEP 91

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 1958770388    3 GKLKVKIVAGRHLPVMDRASDLtDAFVEV-----KFGNTTFKTDVYLKSLNPQWNsewFKFeVWFQVDDEDLQDEPLQIT 77
Cdd:cd04020     27 GELHVWVKEAKNLPALKSGGTS-DSFVKCyllpdKSKKSKQKTPVVKKSVNPVWN---HTF-VYDGVSPEDLSQACLELT 101

                           90
                   ....*....|....*.
gi 1958770388   78 VLDHDTYSANDAIGKV 93
Cdd:cd04020    102 VWDHDKLSSNDFLGGV 117

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 1958770388    3 GKLKVKIVAGRHLPVMDrASDLTDAFVEVKFGN---TTFKTDVYLKSLNPQWNsEWFKFEVWFqvddEDLQDEPLQITVL 79
Cdd:cd08385     16 NQLTVGIIQAADLPAMD-MGGTSDPYVKVYLLPdkkKKFETKVHRKTLNPVFN-ETFTFKVPY----SELGNKTLVFSVY 89

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1958770388   80 DHDTYSANDAIGKVYIdidPLLYSEAATVISGW 112
Cdd:cd08385     90 DFDRFSKHDLIGEVRV---PLLTVDLGHVTEEW 119

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    1 MPGKLKVKIVAGRHLPVMDrASDLTDAFVEV--KFGNTTF---KTDVYLKSLNPQWNsEWFKFEVWFqvddEDLQDEPLQ 75
Cdd:cd08405     13 TANRITVNIIKARNLKAMD-INGTSDPYVKVwlMYKDKRVekkKTVIKKRTLNPVFN-ESFIFNIPL----ERLRETTLI 86

                           90       100
                   ....*....|....*....|
gi 1958770388   76 ITVLDHDTYSANDAIGKVYI 95
Cdd:cd08405     87 ITVMDKDRLSRNDLIGKIYL 106

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    4 KLKVKIVAGRHLPVMDRaSDLTDAFVEVKF-----GNTTFKTDVYLKSLNPQWNSewfKFEvwFQVDDEDLQDEPLQITV 78
Cdd:cd04030     17 KLIVTVHKCRNLPPCDS-SDIPDPYVRLYLlpdksKSTRRKTSVKKDNLNPVFDE---TFE--FPVSLEELKRRTLDVAV 90

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1958770388   79 LDHDTY--SANDAIGKVYIDIDPLLYSEAATvisGWF 113
Cdd:cd04030     91 KNSKSFlsREKKLLGQVLIDLSDLDLSKGFT---QWY 124

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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-II topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    4 KLKVKIVAGRHLPVMDRAsDLTDAFVEVKFGNTTFKTDVYLKSLNPQWNSewfKFEvwFQVDD-EDLQDEPLQITVLdHD 82
Cdd:cd04022      1 KLVVEVVDAQDLMPKDGQ-GSSSAYVELDFDGQKKRTRTKPKDLNPVWNE---KLV--FNVSDpSRLSNLVLEVYVY-ND 73

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1958770388   83 TYS--ANDAIGKVYIDIDPLL-YSEAATVisgWFPI 115
Cdd:cd04022     74 RRSgrRRSFLGRVRISGTSFVpPSEAVVQ---RYPL 106

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 1958770388    5 LKVKIVAGRHLPVMDRASdLTDAFVEVKF-----GNTTFKTDVYLKSLNPQWNSEWfkfeVWFQVDDEDLQDEPLQITVL 79
Cdd:cd04031     18 LIVTVLQARDLPPRDDGS-LRNPYVKVYLlpdrsEKSKRRTKTVKKTLNPEWNQTF----EYSNVRRETLKERTLEVTVW 92

                           90
                   ....*....|....*..
gi 1958770388   80 DHDTYSANDAIGKVYID 96
Cdd:cd04031     93 DYDRDGENDFLGEVVID 109

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    5 LKVKIVAGRHLPVmdRASDLTDAFVEVKFGNT----TFKTDVYLKSLNPQWNsEWFKFEV---------WFQVDDEDLQD 71
Cdd:cd08675      1 LSVRVLECRDLAL--KSNGTCDPFARVTLNYSsktdTKRTKVKKKTNNPRFD-EAFYFELtigfsyekkSFKVEEEDLEK 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1958770388   72 EPLQITVLDHDTYSANDAIGKVYIDIDPLlysEAATVISGWF 113
Cdd:cd08675     78 SELRVELWHASMVSGDDFLGEVRIPLQGL---QQAGSHQAWY 116

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. 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 have a type-II topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    3 GKLKVKIVAGRHLpvmdRASDL---TDAFVEVKFGNTTFKTDVYL-KSLNPQWNsEWFKFEVWFQVDDEDLQdepLQITV 78
Cdd:cd04049      1 GTLEVLLISAKGL----QDTDFlgkIDPYVIIQCRTQERKSKVAKgDGRNPEWN-EKFKFTVEYPGWGGDTK---LILRI 72

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1958770388   79 LDHDTYSANDAIGKVYIDIDPLLyseAATVISGW 112
Cdd:cd04049     73 MDKDNFSDDDFIGEATIHLKGLF---EEGVEPGT 103

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    4 KLKVKIVAGRHLPVMDrASDLTDAFVEVKF--GN---TTFKTDVYLKSLNPQWNSEWfkfeVWFQVDDEDLQDEPLQITV 78
Cdd:cd04035     16 ALHCTIIRAKGLKAMD-ANGLSDPYVKLNLlpGAskaTKLRTKTVHKTRNPEFNETL----TYYGITEEDIQRKTLRLLV 90

                           90
                   ....*....|....*..
gi 1958770388   79 LDHDTYSaNDAIGKVYI 95
Cdd:cd04035     91 LDEDRFG-NDFLGETRI 106

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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 fifth C2 repeat, C2E, and has a type-II topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    7 VKIVAGRHLPVMDRASdLTDAFVEVKFGNTTFKT-DVYL-KSLNPQWNsEWFKFEVWFQVDDEdlqdepLQITVLDHDTY 84
Cdd:cd04037      4 VYVVRARNLQPKDPNG-KSDPYLKIKLGKKKINDrDNYIpNTLNPVFG-KMFELEATLPGNSI------LKISVMDYDLL 75

                           90
                   ....*....|...
gi 1958770388   85 SANDAIGKVYIDI 97
Cdd:cd04037     76 GSDDLIGETVIDL 88

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    5 LKVKIVAGRHLPVMDRASDLTDAFVEVKF---GNTTFKTDVYLKSLNPQWNsEWFKFevwFQVDDEDLQDEPLQITVLDH 81
Cdd:cd08388     18 LLVNIIECRDLPAMDEQSGTSDPYVKLQLlpeKEHKVKTRVLRKTRNPVYD-ETFTF---YGIPYNQLQDLSLHFAVLSF 93

                           90
                   ....*....|....
gi 1958770388   82 DTYSANDAIGKVYI 95
Cdd:cd08388     94 DRYSRDDVIGEVVC 107

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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-II topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    7 VKIVAGRHLPvmdraSDLTDAFVEVKFGNTTFKTDVYLKSLNPQWNsEWFKFEvwFQVDDEDLQDEPLQITVLDHDTYSA 86
Cdd:cd04011      8 VRVIEARQLV-----GGNIDPVVKVEVGGQKKYTSVKKGTNCPFYN-EYFFFN--FHESPDELFDKIIKISVYDSRSLRS 79

                           90
                   ....*....|....*...
gi 1958770388   87 NDAIGKVYIDIdPLLYSE 104
Cdd:cd04011     80 DTLIGSFKLDV-GTVYDQ 96

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    2 PGKLKVKIVAGRHLPVM-DRASDLTDAFVEVK-FG-----NTTFKTDVYLK-SLNPQWNSEwfkFEvwFQVDDEDLQDep 73
Cdd:cd00275      1 PLTLTIKIISGQQLPKPkGDKGSIVDPYVEVEiHGlpaddSAKFKTKVVKNnGFNPVWNET---FE--FDVTVPELAF-- 73

                           90
                   ....*....|....*...
gi 1958770388   74 LQITVLDHDtYSANDAIG 91
Cdd:cd00275     74 LRFVVYDED-SGDDDFLG 90

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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 1958770388    4 KLKVKIVAGRHLPVMDrASDLTDAFVEVKFGNTTFKTDV-YLKSLNPQWNSEwFKFevwfqVDDEDLqDEPLQITVLDHD 82
Cdd:cd04019      1 YLRVTVIEAQDLVPSD-KNRVPEVFVKAQLGNQVLRTRPsQTRNGNPSWNEE-LMF-----VAAEPF-EDHLILSVEDRV 72

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1958770388   83 TYSANDAIGKVYI---DIDPLLysEAATVISGWFPI 115
Cdd:cd04019     73 GPNKDEPLGRAVIplnDIERRV--DDRPVPSRWFSL 106

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    3 GKLKVKIVAGRHLPVMDRASdLTDAFVEVKFGNTT-FKTDVYLKSLNPQWNSEwFKFEVwfQVDDEDLqdepLQITVLDH 81
Cdd:COG5038   1040 GYLTIMLRSGENLPSSDENG-YSDPFVKLFLNEKSvYKTKVVKKTLNPVWNEE-FTIEV--LNRVKDV----LTINVNDW 1111

                           90       100
                   ....*....|....*....|
gi 1958770388   82 DTYSANDAIGKVYIDIDPLL 101
Cdd:COG5038   1112 DSGEKNDLLGTAEIDLSKLE 1131

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958770388   39 KTDVYLKSLNPQWNSEWfkfeVWFQVDDEDLQDEPLQITVLDHDTYSANDAIGKVYIdidPLLYSEAATVISGWFPIY 116
Cdd:cd08381     52 KTKVVRKTRNPTFNEML----VYDGLPVEDLQQRVLQVSVWSHDSLVENEFLGGVCI---PLKKLDLSQETEKWYPLG 122

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958770388    3 GKLKVKIVAGRHLPVMDrASDLTDAFVEVKFGN-----TTFKTDVYLKSLNPQWNsEWFKFevwfQVDDEDLQDEPLQIT 77
Cdd:cd08410     14 GRLNVDIIRAKQLLQTD-MSQGSDPFVKIQLVHglkliKTKKTSCMRGTIDPFYN-ESFSF----KVPQEELENVSLVFT 87

                           90
                   ....*....|....*...
gi 1958770388   78 VLDHDTYSANDAIGKVYI 95
Cdd:cd08410     88 VYGHNVKSSNDFIGRIVI 105