Bestrophin 1

BEST1
Identifiers
Aliases	BEST1, ARB, BEST, BMD, RP50, TU15B, VMD2, Bestrophin 1
External IDs	MGI: 1346332 HomoloGene: 37895 GeneCards: BEST1
Gene ontology Molecular function • chloride channel activity • intracellular calcium activated chloride channel activity • bicarbonate transmembrane transporter activity • identical protein binding Cellular component • integral component of membrane • cytosol • plasma membrane • basolateral plasma membrane • integral component of plasma membrane • membrane • chloride channel complex Biological process • ion transmembrane transport • chloride transport • regulation of calcium ion transport • chloride transmembrane transport • transepithelial chloride transport • ion transport • visual perception • detection of light stimulus involved in visual perception • transport • response to stimulus • bicarbonate transport Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7439	24115
Ensembl	ENSG00000167995	ENSMUSG00000037418
UniProt	O76090	O88870
RefSeq (mRNA)	NM_001139443 NM_001300786 NM_001300787 NM_004183	NM_011913
RefSeq (protein)	NP_001132915.1 NP_001287715.1 NP_001287716.1 NP_004174.1	NP_036043.2
Location (UCSC)	Chr 11: 61.95 – 61.97 Mb	Chr 19: 9.99 – 10 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

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Bestrophin-1 is a protein that in humans is encoded by the BEST1 gene.^[3][4][5]

It can be associated with Vitelliform macular dystrophy.

Function

BEST1 belongs to the bestrophin family of calcium-activated 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 that may also serve as regulators of intracellular calcium signalling.^[6]

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.^[5][7][8]

BEST1 has been shown by two independent studies to be regulated by Microphthalmia-associated transcription factor.^[9][10]

Interactions

Bestrophin 1 has been shown to interact with PPP2CA.^[11]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. 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.
4. 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.
5. "Entrez Gene: BEST1 bestrophin 1".
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. Marmorstein LY, McLaughlin PJ, Stanton JB, Yan L, Crabb JW, Marmorstein AD (2002). "Bestrophin interacts physically and functionally with protein phosphatase 2A". J. Biol. Chem. 277 (34): 30591–7. doi:10.1074/jbc.M204269200. PMID 12058047.

Further reading

• White K, Marquardt A, Weber BH (2000). "VMD2 mutations in vitelliform macular dystrophy (Best disease) and other maculopathies". Hum. Mutat. 15 (4): 301–8. doi:10.1002/(SICI)1098-1004(200004)15:4<301::AID-HUMU1>3.0.CO;2-N. PMID 10737974.
• Nordström S, Barkman Y (1977). "Hereditary maculardegeneration (HMD) in 246 cases traced to one gene-source in central Sweden". Hereditas. 84 (2): 163–76. doi:10.1111/j.1601-5223.1977.tb01394.x. PMID 838599.
• Forsman K, Graff C, Nordström S, et al. (1992). "The gene for Best's macular dystrophy is located at 11q13 in a Swedish family". Clin. Genet. 42 (3): 156–9. doi:10.1111/j.1399-0004.1992.tb03229.x. PMID 1395087.
• Stöhr H, Marquardt A, Rivera A, et al. (1998). "A gene map of the Best's vitelliform macular dystrophy region in chromosome 11q12-q13.1". Genome Res. 8 (1): 48–56. doi:10.1101/gr.8.1.48 (inactive 2016-10-20). PMC 310689. PMID 9445487.
• Petrukhin K, Koisti MJ, Bakall B, et al. (1998). "Identification of the gene responsible for Best macular dystrophy". Nat. Genet. 19 (3): 241–7. doi:10.1038/915. PMID 9662395.
• Pennisi E (1998). "New gene found for inherited macular degeneration". Science. 281 (5373): 31. doi:10.1126/science.281.5373.31. PMID 9679014.
• Marquardt A, Stöhr H, Passmore LA, et al. (1998). "Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best's disease)". Hum. Mol. Genet. 7 (9): 1517–25. doi:10.1093/hmg/7.9.1517. PMID 9700209.
• Caldwell GM, Kakuk LE, Griesinger IB, et al. (1999). "Bestrophin gene mutations in patients with Best vitelliform macular dystrophy". Genomics. 58 (1): 98–101. doi:10.1006/geno.1999.5808. PMID 10331951.
• Bakall B, Marknell T, Ingvast S, et al. (1999). "The mutation spectrum of the bestrophin protein--functional implications". Hum. Genet. 104 (5): 383–9. doi:10.1007/s004390050972. PMID 10394929.
• Allikmets R, Seddon JM, Bernstein PS, et al. (1999). "Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies". Hum. Genet. 104 (6): 449–53. doi:10.1007/s004390050986. PMID 10453731.
• Palomba G, Rozzo C, Angius A, et al. (2000). "A novel spontaneous missense mutation in VMD2 gene is a cause of a best macular dystrophy sporadic case". Am. J. Ophthalmol. 129 (2): 260–2. doi:10.1016/S0002-9394(99)00327-X. PMID 10682987.
• Lotery AJ, Namperumalsamy P, Jacobson SG, et al. (2000). "Mutation analysis of 3 genes in patients with Leber congenital amaurosis". Arch. Ophthalmol. 118 (4): 538–43. doi:10.1001/archopht.118.4.538. PMID 10766140.
• Lotery AJ, Munier FL, Fishman GA, et al. (2000). "Allelic variation in the VMD2 gene in best disease and age-related macular degeneration". Invest. Ophthalmol. Vis. Sci. 41 (6): 1291–6. PMID 10798642.
• Krämer F, White K, Pauleikhoff D, et al. (2000). "Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration". Eur. J. Hum. Genet. 8 (4): 286–92. doi:10.1038/sj.ejhg.5200447. PMID 10854112.
• Marmorstein AD, Marmorstein LY, Rayborn M, et al. (2001). "Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium". Proc. Natl. Acad. Sci. U.S.A. 97 (23): 12758–63. doi:10.1073/pnas.220402097. PMC 18837. PMID 11050159.
• Marchant D, Gogat K, Boutboul S, et al. (2001). "Identification of novel VMD2 gene mutations in patients with best vitelliform macular dystrophy". Hum. Mutat. 17 (3): 235. doi:10.1002/humu.9. PMID 11241846.
• Eksandh L, Bakall B, Bauer B, et al. (2001). "Best's vitelliform macular dystrophy caused by a new mutation (Val89Ala) in the VMD2 gene". Ophthalmic Genet. 22 (2): 107–15. doi:10.1076/opge.22.2.107.2226. PMID 11449320.
• Sun H, Tsunenari T, Yau KW, Nathans J (2002). "The vitelliform macular dystrophy protein defines a new family of chloride channels". Proc. Natl. Acad. Sci. U.S.A. 99 (6): 4008–13. doi:10.1073/pnas.052692999. PMC 122639. PMID 11904445.
• Xiao Q, Yu K, Cui YY, Hartzell HC (2009). "Dysregulation of human bestrophin-1 by ceramide-induced dephosphorylation". J Physiol. 587 (18): 4379–91. doi:10.1113/jphysiol.2009.176800. PMC 2766645. PMID 19635817.
• Xiao Q, Prussia A, Yu K, Cui YY, Hartzell HC (2008). "Regulation of bestrophin Cl channels by calcium: role of the C terminus". J Gen Physiol. 132 (6): 681–92. doi:10.1085/jgp.200810056. PMC 2585866. PMID 19029375.

External links

• GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview

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