{"metadata":{"accession":"PF01062","entry_id":null,"type":"family","go_terms":null,"source_database":"pfam","member_databases":null,"integrated":"IPR021134","hierarchy":null,"name":{"name":"Bestrophin, RFP-TM, chloride channel","short":"Bestrophin"},"description":[{"text":"<p>This entry represents animal bestrophin homologues. Bestrophin is a 68-kDa basolateral plasma membrane protein expressed in retinal pigment epithelial cells (RPE). It is encoded by the VMD2 gene, which is mutated in Best macular dystrophy, a disease characterised by a depressed light peak in the electrooculogram [[cite:PUB00011865]]. VMD2 encodes a 585-amino acid protein with an approximate mass of 68 kDa which has been designated bestrophin. Bestrophin shares homology with the Caenorhabditis elegans RFP gene family, named for the presence of a conserved arginine (R), phenylalanine (F), proline (P), amino acid sequence motif. Bestrophin is a plasma membrane protein, localised to the basolateral surface of RPE cells consistent with a role for bestrophin in the generation or regulation of the EOG light peak. Bestrophin and other RFP family members represent a new class of chloride channels, indicating a direct role for bestrophin in generating the light peak [[cite:PUB00011865]]. The VMD2 gene underlying Best disease was shown to represent the first human member of the RFP-TM protein family. More than 97% of the disease-causing mutations are located in the N-terminal RFP-TM domain implying important functional properties [[cite:PUB00011864]]. The bestrophins are four-pass transmembrane chloride-channel proteins [[cite:PUB00096747]], and the RFP-TM or bestrophin domain extends from the N-terminus through approximately 350 amino acids and contains all of the TM domains as well as nearly all reported disease causing mutations [[cite:PUB00109156]]. Interestingly, the RFP motif is not conserved evolutionarily back beyond Metazoa, neither is it in plant members.</p>","llm":false,"checked":false,"updated":false}],"wikipedia":null,"literature":{"PUB00011864":{"PMID":12032738,"ISBN":null,"volume":"10","issue":"4","year":2002,"title":"Three novel human VMD2-like genes are members of the evolutionary highly conserved RFP-TM family.","URL":null,"raw_pages":"281-4","medline_journal":"Eur J Hum Genet","ISO_journal":"Eur. J. Hum. Genet.","authors":["Stohr H","Marquardt A","Nanda I","Schmid M","Weber BH."],"DOI_URL":"http://dx.doi.org/10.1038/sj.ejhg.5200796"},"PUB00109156":{"PMID":19398034,"ISBN":null,"volume":"28","issue":"3","year":2009,"title":"Functional roles of bestrophins in ocular epithelia.","URL":null,"raw_pages":"206-26","medline_journal":"Prog Retin Eye Res","ISO_journal":"Prog Retin Eye Res","authors":["Marmorstein AD","Cross HE","Peachey NS."],"DOI_URL":null},"PUB00011865":{"PMID":12058047,"ISBN":null,"volume":"277","issue":"34","year":2002,"title":"Bestrophin interacts physically and functionally with protein phosphatase 2A.","URL":null,"raw_pages":"30591-7","medline_journal":"J Biol Chem","ISO_journal":"J. Biol. Chem.","authors":["Marmorstein LY","McLaughlin PJ","Stanton JB","Yan L","Crabb JW","Marmorstein AD."],"DOI_URL":"http://dx.doi.org/10.1074/jbc.M204269200"},"PUB00096747":{"PMID":12907679,"ISBN":null,"volume":"278","issue":"42","year":2003,"title":"Structure-function analysis of the bestrophin family of anion channels.","URL":null,"raw_pages":"41114-25","medline_journal":"J Biol Chem","ISO_journal":"J Biol Chem","authors":["Tsunenari T","Sun H","Williams J","Cahill H","Smallwood P","Yau KW","Nathans J."],"DOI_URL":null}},"set_info":{"accession":"CL0897","name":"Bestrophin"},"overlaps_with":null,"counters":{"subfamilies":0,"domain_architectures":106,"interactions":0,"matches":8846,"pathways":0,"proteins":8246,"proteomes":1318,"sets":1,"structural_models":{"alphafold":7437},"structures":45,"taxa":4218},"entry_annotations":{"hmm":0,"logo":0,"alignment:seed":59,"alignment:full":7212},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":{"accession":"8d1n","name":"bBest2_345 Ca2+-bound open state"}}}