{"metadata":{"accession":"cd08376","entry_id":null,"type":"domain","go_terms":null,"source_database":"cdd","member_databases":null,"integrated":null,"hierarchy":null,"name":{"name":"C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP)","short":"C2B_MCTP_PRT"},"description":[{"text":"<p>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. [[cite:PUB00081546], [cite:PUB00081547], [cite:PUB00005039], [cite:PUB00081548], [cite:PUB00035009], [cite:PUB00000918], [cite:PUB00035040], [cite:PUB00035039]]</p>","llm":false,"checked":false,"updated":false}],"wikipedia":null,"literature":{"PUB00035009":{"PMID":7791877,"ISBN":null,"volume":"375","issue":"6532","year":1995,"title":"Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins.","URL":null,"raw_pages":"594-9","medline_journal":"Nature","ISO_journal":"Nature","authors":["Li C","Ullrich B","Zhang JZ","Anderson RG","Brose N","Sudhof TC."],"DOI_URL":"http://dx.doi.org/10.1038/375594a0"},"PUB00035040":{"PMID":1589771,"ISBN":null,"volume":"256","issue":"5059","year":1992,"title":"Synaptotagmin: a calcium sensor on the synaptic vesicle surface.","URL":null,"raw_pages":"1021-5","medline_journal":"Science","ISO_journal":"Science","authors":["Brose N","Petrenko AG","Sudhof TC","Jahn R."],"DOI_URL":"http://www.sciencemag.org/cgi/content/abstract/256/5059/1021"},"PUB00081548":{"PMID":8662510,"ISBN":null,"volume":"273","issue":"5272","year":1996,"title":"Bipartite Ca2+-binding motif in C2 domains of synaptotagmin and protein kinase C.","URL":null,"raw_pages":"248-51","medline_journal":"Science","ISO_journal":"Science","authors":["Shao X","Davletov BA","Sutton RB","Sudhof TC","Rizo J."],"DOI_URL":"http://dx.doi.org/10.1126/science.273.5272.248"},"PUB00000918":{"PMID":7697723,"ISBN":null,"volume":"80","issue":"6","year":1995,"title":"Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold.","URL":null,"raw_pages":"929-38","medline_journal":"Cell","ISO_journal":"Cell","authors":["Sutton RB","Davletov BA","Berghuis AM","Sudhof TC","Sprang SR."],"DOI_URL":"http://dx.doi.org/10.1016/0092-8674(95)90296-1"},"PUB00005039":{"PMID":8771209,"ISBN":null,"volume":"5","issue":"1","year":1996,"title":"Extending the C2 domain family: C2s in PKCs delta, epsilon, eta, theta, phospholipases, GAPs, and perforin.","URL":null,"raw_pages":"162-6","medline_journal":"Protein Sci","ISO_journal":"Protein Sci.","authors":["Ponting CP","Parker PJ."],"DOI_URL":"http://ukpmc.ac.uk/picrender.cgi?tool=EBI&pubmedid=8771209&action=stream&blobtype=pdf"},"PUB00081547":{"PMID":8976547,"ISBN":null,"volume":"5","issue":"12","year":1996,"title":"The C2 domain calcium-binding motif: structural and functional diversity.","URL":null,"raw_pages":"2375-90","medline_journal":"Protein Sci","ISO_journal":"Protein Sci.","authors":["Nalefski EA","Falke JJ."],"DOI_URL":"http://dx.doi.org/10.1002/pro.5560051201"},"PUB00081546":{"PMID":9632630,"ISBN":null,"volume":"273","issue":"26","year":1998,"title":"C2-domains, structure and function of a universal Ca2+-binding domain.","URL":null,"raw_pages":"15879-82","medline_journal":"J Biol Chem","ISO_journal":"J. Biol. Chem.","authors":["Rizo J","Sudhof TC."],"DOI_URL":"http://dx.doi.org/10.1074/jbc.273.26.15879"},"PUB00035039":{"PMID":2333096,"ISBN":null,"volume":"345","issue":"6272","year":1990,"title":"Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C.","URL":null,"raw_pages":"260-3","medline_journal":"Nature","ISO_journal":"Nature","authors":["Perin MS","Fried VA","Mignery GA","Jahn R","Sudhof TC."],"DOI_URL":"http://dx.doi.org/10.1038/345260a0"}},"set_info":{"accession":"cl14603","name":"C2"},"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":0,"interactions":0,"matches":4154,"pathways":0,"proteins":4154,"proteomes":925,"sets":1,"structural_models":{"alphafold":3709,"bfvd":0},"structures":0,"taxa":3359},"entry_annotations":{},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":null}}