TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*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).

Eukaryota
Metazoa
Bestrophin-1 of Homo sapiens (O76090)
*1.A.46.1.2









Bestrophin-2 anion channel (PNO3-/PCl- = 2.7) (Sun et al., 2002).  The mouse orthologue is swell-insensitive, but the first 64 aas of Bestrophin 1 of Drosophila melanogaster allowed it to mediate cell swelling in response to hypo-osmotic stress (Stotz and Clapham 2012).

Eukaryota
Metazoa
Bestrophin-2 of Homo sapiens (AAM76995)
*1.A.46.1.3









Bestrophin family anion channel, YxaK (Protein R13.3) (Sun et al., 2002)
Eukaryota
Metazoa
YxaK of Caenorhabditis elegans (Q21973)
*1.A.46.1.4









Bestrophin 3 vitelliform macular dystrophy 2-like protein 3 (possesses a C-terminal motif blocking its own channel activity (Qu et al., 2006).  Ca2+ activates anion flux with SCN->I->Cl-.
Eukaryota
Metazoa
Best3 of Mus musculus
(Q6H1V1)
*1.A.46.1.5









Bestrophin1, isoform B.  Identified as the Cl- (swell) channel that allows swelling in hypo-osmotic solutions (Stotz and Clapham 2012).  Its N-terminal 64 aas are essential for swell activation. 

Eukaryota
Metazoa
Bestrophin1 of Drosophila melanogaster (B7Z0U6)
*1.A.46.1.6









Bestrophin-1 (Best1) of 689 aas and 4 TMSs in a 2 + 2 arrangement.  The x-ray structure has been determined at 2.85 Å resolution with permeant anions and Ca2+ bound (Kane Dickson et al. 2014).  The channel is formed from a pentameric assembly of subunits. Ca2+ binds to the channel's large cytosolic region. A single ion pore, approximately 95 Å in length, is located along the central axis and contains at least 15 binding sites for anions. A hydrophobic neck within the pore probably forms the gate. Phenylalanine residues within it may coordinate permeating anions via anion-π interactions. Conformational changes observed near the 'Ca2+ clasp' hint at the mechanism of Ca2+-dependent gating (Kane Dickson et al. 2014).

Eukaryota
Metazoa
Best1 of Gallus gallus (chicken)
*1.A.46.2.1









Plasma membrane Ca2+-activated anion-selective channel, Best1 (AN2251) of 499 aas and 4 TMSs. Transports citrate, propionate, benzoate, and sorbate (Roberts et al., 2011).

Eukaryota
Fungi
Best1 of Aspergillus nidulans (Q5BB29)
*1.A.46.2.2









Fungal Best2 protein, AN6909 (Roberts et al., 2011) (29% identical to Best1 (TC# 1.A.46.2.1)).

Eukaryota
Fungi
Best2 of Aspergillus nidulans (Q5AXS1)
*1.A.46.2.3









Bestrophin homologue 

Bacteria
Cyanobacteria
Bestrophin homologue of Cyanothece sp. PCC8801 (B7K217)
*1.A.46.2.4









Bestrophin homologue

Bacteria
Firmicutes
Bestrophin homologue of Bacillus cereus (C2UY63)
*1.A.46.2.5









Bestrophin homologue 

Bacteria
Proteobacteria
Bestrophin homologue of Bdellovibrio bacteriovorus (Q6MLK6)
*1.A.46.2.6









Bestrophin homologue, YneE 

Bacteria
Proteobacteria
YneE of E. coli (B2N0W4)
*1.A.46.2.7









Chloroplast bestrophin homologue of 410 aas and 4 or 5 TMSs, VCCN1. Plants adjust photosynthetic light utilization by controlling electron transport and photoprotective mechanisms, and this involves the proton motive force (PMF) across the thylakoid membrane. VCCN1 is a voltage-dependent Cl- channel which localizes to the thylakoid membrane and fine-tunes the PMF by anion influx into the lumen during illumination, adjusting electron transport and photoprotective mechanisms (Herdean et al. 2016). The activity of AtVCCN1 accelerates the activation of photoprotective mechanisms on sudden shifts to high light. Thus, AtVCCN1 acts as an early component in the rapid adjustment of photosynthesis in variable light intensities.

Eukaryota
Viridiplantae
Bestrophin homologue of Arabidopsis thaliana (Q9M2D2)
*1.A.46.2.8









Functionally characterized bestrophin homologue, KpBEST, YneE or RFP-TM of 305 aas and 3 or 4 TMSs per subunit.  KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit (Yang et al. 2014). From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, a sensitive control of ion selectivity was observed in the bestrophins, including reversal of anion/cation selectivity, and dramatic activation by mutations at the cytoplasmic exit.  The wild type protein seems to be a cation (Na+) channel but the I66F mutation changed it into an anion (Cl-) channel (Yang et al. 2014).  There are two  constrictions in the channel, one provides the ion selectivity and the other serves as the gate.

Bacteria
Proteobacteria
KpBEST of Klebsiella pneumoniae
*1.A.46.2.9









Uncharacterized protein of 895 aas and 10 TMSs in a 2 + 2 + 2 + 2 + 2 arrangement.  There appear to be two full length repeats, each of 4 TMSs, plus and extra C-terminal two TMSs, all homologous to each other.

Eukaryota
Viridiplantae
UP of Ostreococcus lucimarinus
*1.A.46.2.10









Bestrophin homologue of 361 aas and 2 - 4 TMSs.

Eukaryota
Bangiophyceae
Best protein of Galdieria sulphuraria (Red alga)
*1.A.46.2.11









Bestrophin homologue of 446 aas and ~ 4 TMSs.

Eukaryota
Viridiplantae
Best protein of Volvox carteri