C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). 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 type-II topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706  13 KLRLTVLCAKNLVKKDFFRLPDPFAKVVVDGsGQCHSTDTVKNTLDPKWNQHYDLYIGKSDSVTISVWNHKKIHKKQgAG 92
Cdd:cd08382     1 KVRLTVLCADGLAKRDLFRLPDPFAVITVDG-GQTHSTDVAKKTLDPKWNEHFDLTVGPSSIITIQVFDQKKFKKKD-QG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1907082706  93 FLGCVRLLSNAINRLKDTGYQRLDLCKLGPNDNDTVRGQIVVSLQ 137
Cdd:cd08382    79 FLGCVRIRANAVLPLKDTGYQRLDLRKLKKSDNLSVRGKIVVSLS 123

HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ubiquitin molecules to the end of growing ubiquitin chains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706 393 CRIEVSREEIFEESYRQVMKMRPKDLWKRLMIKFRGEEGLDYGGVAREWLYLLSHEMLNPYYGLFQYSRDDIYTLQINPD 472
Cdd:cd00078     1 LKITVRRDRILEDALRQLSKVSSSDLKKVLEVEFVGEEGIDAGGVTREFFTLVSKELFNPSYGLFRYTPDDSGLLYPNPS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706 473 SAVNPEHLSYFHFVGRIMGMAVFHGHYIDGGFTLPFYKQLLGKSITLDDMELVDPDLHNSLVWILENDI-TGVLDHTFCV 551
Cdd:cd00078    81 SFADEDHLKLFRFLGRLLGKALYEGRLLDLPFSRAFYKKLLGKPLSLEDLEELDPELYKSLKELLDNDGdEDDLELTFTI 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907082706 552 EHN-AYGEIIQHELKPNGKSIPVTEENKKEYVRLYVNWRFLRGIEAQFLALQKGFNEVIPQHLLKTFDEKELEVL 625
Cdd:cd00078   161 ELDsSFGGAVTVELKPGGRDIPVTNENKEEYVDLYVDYRLNKGIEEQVEAFRDGFSEVIPEELLSLFTPEELELL 235

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). 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 type-II topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706  13 KLRLTVLCAKNLVKKDFFRLPDPFAKVVVDGsGQCHSTDTVKNTLDPKWNQHYDLYIGKSDSVTISVWNHKKIHKKQgAG 92
Cdd:cd08382     1 KVRLTVLCADGLAKRDLFRLPDPFAVITVDG-GQTHSTDVAKKTLDPKWNEHFDLTVGPSSIITIQVFDQKKFKKKD-QG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1907082706  93 FLGCVRLLSNAINRLKDTGYQRLDLCKLGPNDNDTVRGQIVVSLQ 137
Cdd:cd08382    79 FLGCVRIRANAVLPLKDTGYQRLDLRKLKKSDNLSVRGKIVVSLS 123

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706  13 KLRLTVLCAKNLVKKDFFRLPDPFAKVVVDGSGQCHSTDTVKNTLDPKWNQH--YDLYIGKSDSVTISVWNHKKIHKKQg 90
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETftFSVPDPENAVLEIEVYDYDRFGRDD- 80

                  ....*....
gi 1907082706  91 agFLGCVRL 99
Cdd:pfam00168  81 --FIGEVRI 87

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706   14 LRLTVLCAKNLVKKDFF--RLPDPFakVVVDGSGQCH-STDTVKNTLDPKWNQHYDLYIGK-SDSVTISVW--NHKKIHK 87
Cdd:COG5038    438 VEVKIKSAEGLKKSDSTinGTVDPY--ITVTFSDRVIgKTRVKKNTLNPVWNETFYILLNSfTDPLNLSLYdfNSFKSDK 515

                           90
                   ....*....|....*
gi 1907082706   88 KQGAGFLGCVRLLSN 102
Cdd:COG5038    516 VVGSTQLDLALLHQN 530

HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ubiquitin molecules to the end of growing ubiquitin chains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706 393 CRIEVSREEIFEESYRQVMKMRPKDLWKRLMIKFRGEEGLDYGGVAREWLYLLSHEMLNPYYGLFQYSRDDIYTLQINPD 472
Cdd:cd00078     1 LKITVRRDRILEDALRQLSKVSSSDLKKVLEVEFVGEEGIDAGGVTREFFTLVSKELFNPSYGLFRYTPDDSGLLYPNPS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706 473 SAVNPEHLSYFHFVGRIMGMAVFHGHYIDGGFTLPFYKQLLGKSITLDDMELVDPDLHNSLVWILENDI-TGVLDHTFCV 551
Cdd:cd00078    81 SFADEDHLKLFRFLGRLLGKALYEGRLLDLPFSRAFYKKLLGKPLSLEDLEELDPELYKSLKELLDNDGdEDDLELTFTI 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907082706 552 EHN-AYGEIIQHELKPNGKSIPVTEENKKEYVRLYVNWRFLRGIEAQFLALQKGFNEVIPQHLLKTFDEKELEVL 625
Cdd:cd00078   161 ELDsSFGGAVTVELKPGGRDIPVTNENKEEYVDLYVDYRLNKGIEEQVEAFRDGFSEVIPEELLSLFTPEELELL 235

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). 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 type-II topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706  13 KLRLTVLCAKNLVKKDFFRLPDPFAKVVVDGsGQCHSTDTVKNTLDPKWNQHYDLYIGKSDSVTISVWNHKKIHKKQgAG 92
Cdd:cd08382     1 KVRLTVLCADGLAKRDLFRLPDPFAVITVDG-GQTHSTDVAKKTLDPKWNEHFDLTVGPSSIITIQVFDQKKFKKKD-QG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1907082706  93 FLGCVRLLSNAINRLKDTGYQRLDLCKLGPNDNDTVRGQIVVSLQ 137
Cdd:cd08382    79 FLGCVRIRANAVLPLKDTGYQRLDLRKLKKSDNLSVRGKIVVSLS 123

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706  13 KLRLTVLCAKNLVKKDFFRLPDPFAKVVVDGSGQCHSTDTVKNTLDPKWNQH--YDLYIGKSDSVTISVWNHKKIHKKQg 90
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDGNGTSDPYVKVYLLDGKQKKKTKVVKNTLNPVWNETftFSVPDPENAVLEIEVYDYDRFGRDD- 80

                  ....*....
gi 1907082706  91 agFLGCVRL 99
Cdd:pfam00168  81 --FIGEVRI 87

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 1907082706   13 KLRLTVLCAKNLVKKDFFRLPDPFAKVVVDG-SGQCHSTDTVKNTLDPKWNQHYDLYI--GKSDSVTISVWNHKKIHKKQ 89
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGdPKEKKKTKVVKNTLNPVWNETFEFEVppPELAELEIEVYDKDRFGRDD 80

                           90
                   ....*....|
gi 1907082706   90 gagFLGCVRL 99
Cdd:smart00239  81 ---FIGQVTI 87

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. 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 1907082706  15 RLTVLCAKNLVKKDFFRLPDPFakVVVDGSGQCHSTDTVKNTLDPKWNQHYDLYIGKSDS-VTISVWNHKKIhkkqGAGF 93
Cdd:cd04046     6 QVHVHSAEGLSKQDSGGGADPY--VIIKCEGESVRSPVQKDTLSPEFDTQAIFYRKKPRSpIKIQVWNSNLL----CDEF 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1907082706  94 LGCVRLlsnAINRLKDTGYQRLDLCKLGPNDNDTVRGQIVVSLQSRD 140
Cdd:cd04046    80 LGQATL---SADPNDSQTLRTLPLRKRGRDAAGEVPGTISVKVTSSD 123

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1907082706  158 DLPDGWEERRTASGRIQYLNHITRTTQWERPT 189
Cdd:smart00456   1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPR 32

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                          10        20        30
                  ....*....|....*....|....*....|.
gi 1907082706 300 PPGWEIRNTATGRVYFVDHNNRTTQFTDPRL 330
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPRE 31

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907082706  13 KLRLTVLCAKNLVKKDFFRlPDPFAKVVVDGSGQcHSTDTVKNTLDPKWNQHYDLYIGKSDSVTISVWNHKKIHKKQ 89
Cdd:cd04021     3 QLQITVESAKLKSNSKSFK-PDPYVEVTVDGQPP-KKTEVSKKTSNPKWNEHFTVLVTPQSTLEFKVWSHHTLKADV 77

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 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 1907082706  14 LRLTVLCAKNLVKKDFFRL--PDPFAKVVVdGSGQcHSTDTVKNTLDPKWNQHYD--LYIGKSDSVTISVWNHKKIHKKQ 89
Cdd:cd04024     3 LRVHVVEAKDLAAKDRSGKgkSDPYAILSV-GAQR-FKTQTIPNTLNPKWNYWCEfpIFSAQNQLLKLILWDKDRFAGKD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907082706  90 gagFLG--CVRLLSNAINRLKDTGYQRLDLCKLGPNDNDTVRGQIVVSLQ 137
Cdd:cd04024    81 ---YLGefDIALEEVFADGKTGQSDKWITLKSTRPGKTSVVSGEIHLQFS 127

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 1907082706  13 KLRLTVLCAKNLVKKDFFRLPDPFakVVVDGSGQCHSTDTVKNTLDPKWNQHYDLYIGK-----SDSVTISVWNHKKihK 87
Cdd:cd04022     1 KLVVEVVDAQDLMPKDGQGSSSAY--VELDFDGQKKRTRTKPKDLNPVWNEKLVFNVSDpsrlsNLVLEVYVYNDRR--S 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1907082706  88 KQGAGFLGCVRLLSNAINRLKDTGYQRLDLCKLGPNDNdtVRGQI 132
Cdd:cd04022    77 GRRRSFLGRVRISGTSFVPPSEAVVQRYPLEKRGLFSR--VRGEI 119

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding 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 second C2 repeat, C2B, and has a type-II topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706  12 VKLRLTVLCAKNLVKKDFFRLPDPFA------------------------KVVVDG---SGQCHSTDTVKNTLDPKWNQH 64
Cdd:cd08676    28 FVLKVTVIEAKGLLAKDVNGFSDPYCmlgivpasrernsekskkrkshrkKAVLKDtvpAKSIKVTEVKPQTLNPVWNET 107

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907082706  65 YDLYIG--KSDSVTISVWNHkkihkkqGAGFLGCVRLlsnainRLKDTGYQRLD 116
Cdd:cd08676   108 FRFEVEdvSNDQLHLDIWDH-------DDDFLGCVNI------PLKDLPSCGLD 148

Domain with 2 conserved Trp (W) residues; Also known as the WWP or rsp5 domain. Binds proline-rich polypeptides.

                           10        20        30
                   ....*....|....*....|....*....|..
gi 1907082706  252 DLPEGYEQRTTQQGQVYFLHTQTGVSTWHDPR 283
Cdd:smart00456   1 PLPPGWEERKDPDGRPYYYNHETKETQWEKPR 32

WW domain; The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1907082706 253 LPEGYEQRTTQQGQVYFLHTQTGVSTWHDP 282
Cdd:pfam00397   1 LPPGWEERWDPDGRVYYYNHETGETQWEKP 30

Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other peptide recognition proteins such as antibodies and receptors; WW domains have a single groove formed by a conserved Trp and Tyr which recognizes a pair of residues of the sequence X-Pro; variable loops and neighboring domains confer specificity in this domain; there are five distinct groups based on binding: 1) PPXY motifs 2) the PPLP motif; 3) PGM motifs; 4) PSP or PTP motifs; 5) PR motifs.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1907082706 254 PEGYEQRTTQQGQVYFLHTQTGVSTWHDPR 283
Cdd:cd00201     1 PPGWEERWDPDGRVYYYNHNTKETQWEDPR 30

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907082706  14 LRLTVLCAKNLVKKDFFRLPDPFAKVV-----VDGSGQchSTDTVKNTLDPKWNQ 63
Cdd:cd04031    18 LIVTVLQARDLPPRDDGSLRNPYVKVYllpdrSEKSKR--RTKTVKKTLNPEWNQ 70

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 1907082706  13 KLRLTVLCAKNLVKKDFFRLPDPFAKVVVDgsGQCHSTDTVKNTLDPKWNQ--HYDLYIGKSDSVTISVWNHKKIHKKQg 90
Cdd:cd04025     1 RLRCHVLEARDLAPKDRNGTSDPFVRVFYN--GQTLETSVVKKSCYPRWNEvfEFELMEGADSPLSVEVWDWDLVSKND- 77

                  ....*..
gi 1907082706  91 agFLGCV 97
Cdd:cd04025    78 --FLGKV 82

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding 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 second C2 repeat, C2B, and has a type-II topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706  13 KLRLTVLCAKNLVKKDFFRLPDPFAKVVVDGSGQchSTDTVKNTLDPKWNQ--HYDLYiGKSDSVTISVWNH-------- 82
Cdd:cd04027     2 KISITVVCAQGLIAKDKTGTSDPYVTVQVGKTKK--RTKTIPQNLNPVWNEkfHFECH-NSSDRIKVRVWDEdddiksrl 78

                          90       100
                  ....*....|....*....|...
gi 1907082706  83 KKIHKKQGAGFLGC----VRLLS 101
Cdd:cd04027    79 KQKFTRESDDFLGQtiieVRTLS 101

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH 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. The members here have topology I.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706   7 RRNGPVKLRLTVLCAKNLVKKDFFRLPDPFAKVVVdGSgQCHSTDTVKNTLDPKWN-----QHYDLYigkSDSVTISVWN 81
Cdd:cd08375    10 RASGIGRLMVVIVEGRDLKPCNSNGKSDPYCEVSM-GS-QEHKTKVVSDTLNPKWNssmqfFVKDLE---QDVLCITVFD 84

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907082706  13 KLRLTVLCAKNLVKKDFfRLPDPFAKV--VVDGSGQC-HSTDTVKNTLDPKWNQHYDLYIGKSDS---VTISVWNhkKIH 86
Cdd:cd08685    13 KLTLHVLEAKGLRSTNS-GTCNSYVKIslSPDKEVRFrQKTSTVPDSANPLFHETFSFDVNERDYqkrLLVTVWN--KLS 89

                          90
                  ....*....|
gi 1907082706  87 KKQGAGFLGC 96
Cdd:cd08685    90 KSRDSGLLGC 99

C2 domain third 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 third C2 repeat, C2C, and has a type-II topology.