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1.A.46.1.1
Bestrophin-1 (Best1) anion channel; VMD2 gene product (NO3- > I- > Br- > Cl-; PNO3-/PCl- = 5.8) (Sun et al., 2002). Regulated by ceramide-induced dephosphorylation (Xiao et al., 2009).  Best1 mediates fast and slow glutamate release in astrocytes upon GPCR activation (Woo et al. 2012).  Progressive posterior chorioretinal changes occur over time in the initial ADVIRC proband, leading to visual loss. The causative mutation is in the transmembrane domain of BEST1 (Chen et al. 2016).  Autosomal dominant vitreoretinochoroidopathy (ADVIRC), caused by mutation in BEST-1, is a rare, early-onset retinal dystrophy characterised by distinct bands of circumferential pigmentary degeneration in the peripheral retina accompanied by developmental eye defects. It is an ion channel in the basolateral membrane of retinal pigment epithelial (RPE) cells.In patients, BEST1 is expressed at the basolateral membrane and the apical membrane. During human eye development, BEST1 is expressed more abundantly in peripheral RPE compared to central RPE and is also expressed in cells of the developing retina. Higher levels of mislocalised BEST1 expression in the periphery, from an early developmental stage, may provide the mechanism that leads to the distinct clinical phenotype observed in ADVIRC patients (Carter et al. 2016).  Binding of Ca2+ induces conformational changes in the secondary structure leading to assembly of monomers and changes in molecular and macro-organization (Mladenova et al. 2016).

Accession Number:O76090
Protein Name:Bestrophin-1 aka VMD2
Length:585
Molecular Weight:67684.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:4
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate nitrate, I-, Br-, Cl-

Cross database links:

Genevestigator: O76090
eggNOG: prNOG06628
RefSeq: NP_001132915.1    NP_004174.1   
Entrez Gene ID: 7439   
Pfam: PF01062   
OMIM: 153700  phenotype
153870  phenotype
193220  phenotype
607854  gene
608161  phenotype
611809  phenotype
KEGG: hsa:7439   

Gene Ontology

GO:0016323 C:basolateral plasma membrane
GO:0034707 C:chloride channel complex
GO:0005829 C:cytosol
GO:0005624 C:membrane fraction
GO:0005254 F:chloride channel activity
GO:0050896 P:response to stimulus
GO:0030321 P:transepithelial chloride transport
GO:0007601 P:visual perception

References (24)

[1] “Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best's disease).”  Marquardt A.et.al.   9700209
[2] “Identification of the gene responsible for Best macular dystrophy.”  Petrukhin K.et.al.   9662395
[3] “Structure-function analysis of the bestrophin family of anion channels.”  Tsunenari T.et.al.   12907679
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[6] “The vitelliform macular dystrophy protein defines a new family of chloride channels.”  Sun H.et.al.   11904445
[7] “Bestrophin Cl- channels are highly permeable to HCO3-.”  Qu Z.et.al.   18400985
[8] “Bestrophin gene mutations in patients with Best vitelliform macular dystrophy.”  Caldwell G.M.et.al.   10331951
[9] “The mutation spectrum of the bestrophin protein -- functional implications.”  Bakall B.et.al.   10394929
[10] “Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies.”  Allikmets R.et.al.   10453731
[11] “A novel spontaneous missense mutation in VMD2 gene is a cause of a Best macular dystrophy sporadic case.”  Palomba G.et.al.   10682987
[12] “Mutation analysis of 3 genes in patients with Leber congenital amaurosis.”  Lotery A.J.et.al.   10766140
[13] “Allelic variation in the VMD2 gene in best disease and age-related macular degeneration.”  Lotery A.J.et.al.   10798642
[14] “Identification of novel VMD2 gene mutations in patients with Best vitelliform macular dystrophy.”  Marchant D.et.al.   11241846
[15] “Best's vitelliform macular dystrophy caused by a new mutation (Val89Ala) in the VMD2 gene.”  Eksandh L.et.al.   11449320
[16] “Identification of a novel VMD2 mutation in Japanese patients with Best disease.”  Yanagi Y.et.al.   12187431
[17] “Use of denaturing HPLC and automated sequencing to screen the VMD2 gene for mutations associated with Best's vitelliform macular dystrophy.”  Marchant D.et.al.   12324875
[18] “Ten novel mutations in VMD2 associated with Best macular dystrophy (BMD).”  Kraemer F.et.al.   14517959
[19] “Phenotype and genotype correlations in two best families.”  Seddon J.M.et.al.   13129869
[20] “Gene Symbol: VMD2. Disease: Best vitelliform macular dystrophy (VMD2).”  Li Y.et.al.   15176385
[21] “Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC).”  Yardley J.et.al.   15452077
[22] “Biallelic mutation of BEST1 causes a distinct retinopathy in humans.”  Burgess R.et.al.   18179881
[23] “Mutation analysis of the VMD2 gene in thai families with Best macular dystrophy.”  Atchaneeyasakul L.O.et.al.   18766995
[24] “Clinical and molecular genetic analysis of Best vitelliform macular dystrophy.”  Boon C.J.F.et.al.   19357557

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MTITYTSQVA NARLGSFSRL LLCWRGSIYK LLYGEFLIFL LCYYIIRFIY RLALTEEQQL 
61:	MFEKLTLYCD SYIQLIPISF VLGFYVTLVV TRWWNQYENL PWPDRLMSLV SGFVEGKDEQ 
121:	GRLLRRTLIR YANLGNVLIL RSVSTAVYKR FPSAQHLVQA GFMTPAEHKQ LEKLSLPHNM 
181:	FWVPWVWFAN LSMKAWLGGR IRDPILLQSL LNEMNTLRTQ CGHLYAYDWI SIPLVYTQVV 
241:	TVAVYSFFLT CLVGRQFLNP AKAYPGHELD LVVPVFTFLQ FFFYVGWLKV AEQLINPFGE 
301:	DDDDFETNWI VDRNLQVSLL AVDEMHQDLP RMEPDMYWNK PEPQPPYTAA SAQFRRASFM 
361:	GSTFNISLNK EEMEFQPNQE DEEDAHAGII GRFLGLQSHD HHPPRANSRT KLLWPKRESL 
421:	LHEGLPKNHK AAKQNVRGQE DNKAWKLKAV DAFKSAPLYQ RPGYYSAPQT PLSPTPMFFP 
481:	LEPSAPSKLH SVTGIDTKDK SLKTVSSGAK KSFELLSESD GALMEHPEVS QVRRKTVEFN 
541:	LTDMPEIPEN HLKEPLEQSP TNIHTTLKDH MDPYWALENR DEAHS