Bestrophin 1

Bestrophin 1
Identifiers
Symbols BEST1; ARB; BEST; BMD; RP50; TU15B; VMD2
External IDs OMIM: 607854 MGI: 1346332 HomoloGene: 37895 GeneCards: BEST1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 7439 24115
Ensembl ENSG00000167995 ENSMUSG00000037418
UniProt O76090 O88870
RefSeq (mRNA) NM_001139443.1 NM_011913.2
RefSeq (protein) NP_001132915.1 NP_036043.2
Location (UCSC) Chr 11:
61.72 – 61.73 Mb		 Chr 19:
10.06 – 10.08 Mb
PubMed search [1] [2]

Bestrophin-1 is a protein that in humans is encoded by the BEST1 gene.[1][2][3]

It can be associated with Vitelliform macular dystrophy.

Contents

Function

BEST1 belongs to the bestrophin family of anion channels, which includes BEST2, BEST3, and BEST4. Bestrophins are transmembrane (TM) proteins that share a homology region containing a high content of aromatic residues, including an invariant arg-phe-pro (RFP) motif. Bestrophins are believed to function as chloride channels.[4]

Bestrophin 1 was shown to be permeable for chloride, thiocyanate, bicarbonate, glutamate, and GABA. Bestrophin 1-mediated GABA release has recently been demonstrated to be responsible for tonic inhibition in cerebellar granule cells.[5]

Gene structure

The bestrophin genes share a conserved gene structure, with almost identical sizes of the 8 RFP-TM domain-encoding exons and highly conserved exon-intron boundaries. Each of the 4 bestrophin genes has a unique 3-prime end of variable length.[3][6][7]

BEST1 has been shown by two independent studies to be regulated by Microphthalmia-associated transcription factor.[8][9]

Interactions

Bestrophin 1 has been shown to interact with PPP2CA.[10]

References

  1. ^ Stone EM, Nichols BE, Streb LM, Kimura AE, Sheffield VC (Jun 1993). "Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13". Nat Genet 1 (4): 246–50. doi:10.1038/ng0792-246. PMID 1302019. 
  2. ^ Barro Soria R, Spitzner M, Schreiber R, Kunzelmann K (Sep 2006). "Bestrophin 1 enables Ca2+ activated Cl- conductance in epithelia". J Biol Chem 284 (43): 29405–12. doi:10.1074/jbc.M605716200. PMC 2785573. PMID 17003041. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2785573. 
  3. ^ a b "Entrez Gene: BEST1 bestrophin 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7439. 
  4. ^ Hartzell HC, Qu Z, Yu K, Xiao Q, Chien LT (April 2008). "Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies". Physiol. Rev. 88 (2): 639–72. doi:10.1152/physrev.00022.2007. PMID 18391176. 
  5. ^ Lee S, Yoon BE, Berglund K, Oh SJ, Park H, Shin HS, Augustine GJ, Lee CJ (November 2010). "Channel-mediated tonic GABA release from glia". Science 330 (6005): 790–6. doi:10.1126/science.1184334. PMID 20929730. 
  6. ^ Stöhr H, Marquardt A, Nanda I, Schmid M, Weber BH (April 2002). "Three novel human VMD2-like genes are members of the evolutionary highly conserved RFP-TM family". Eur. J. Hum. Genet. 10 (4): 281–4. doi:10.1038/sj.ejhg.5200796. PMID 12032738. 
  7. ^ Tsunenari T, Sun H, Williams J, Cahill H, Smallwood P, Yau KW, Nathans J (October 2003). "Structure-function analysis of the bestrophin family of anion channels". J. Biol. Chem. 278 (42): 41114–25. doi:10.1074/jbc.M306150200. PMC 2885917. PMID 12907679. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2885917. 
  8. ^ Esumi N, Kachi S, Campochiaro PA, Zack DJ (2007). "VMD2 promoter requires two proximal E-box sites for its activity in vivo and is regulated by the MITF-TFE family". J. Biol. Chem. 282 (3): 1838–50. doi:10.1074/jbc.M609517200. PMID 17085443. 
  9. ^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
  10. ^ Marmorstein, Lihua Y; McLaughlin Precious J, Stanton J Brett, Yan Lin, Crabb John W, Marmorstein Alan D (Aug. 2002). "Bestrophin interacts physically and functionally with protein phosphatase 2A". J. Biol. Chem. (United States) 277 (34): 30591–7. doi:10.1074/jbc.M204269200. ISSN 0021-9258. PMID 12058047. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.