BEST4_HUMAN
ID BEST4_HUMAN Reviewed; 473 AA.
AC Q8NFU0; Q5JR93;
DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Bestrophin-4;
DE AltName: Full=Vitelliform macular dystrophy 2-like protein 2;
GN Name=BEST4; Synonyms=VMD2L2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=12032738; DOI=10.1038/sj.ejhg.5200796;
RA Stoehr H., Marquardt A., Nanda I., Schmid M., Weber B.H.F.;
RT "Three novel human VMD2-like genes are members of the evolutionary highly
RT conserved RFP-TM family.";
RL Eur. J. Hum. Genet. 10:281-284(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=12907679; DOI=10.1074/jbc.m306150200;
RA Tsunenari T., Sun H., Williams J., Cahill H., Smallwood P., Yau K.-W.,
RA Nathans J.;
RT "Structure-function analysis of the bestrophin family of anion channels.";
RL J. Biol. Chem. 278:41114-41125(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=18400985; DOI=10.1152/ajpcell.00398.2007;
RA Qu Z., Hartzell H.C.;
RT "Bestrophin Cl- channels are highly permeable to HCO3-.";
RL Am. J. Physiol. 294:C1371-C1377(2008).
CC -!- FUNCTION: Forms calcium-sensitive chloride channels. Permeable to
CC bicarbonate. {ECO:0000269|PubMed:12907679,
CC ECO:0000269|PubMed:18400985}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Predominantly found in colon and the weakly in
CC fetal brain, spinal cord, retina, lung, trachea, testis and placenta.
CC {ECO:0000269|PubMed:12032738}.
CC -!- SIMILARITY: Belongs to the bestrophin family. {ECO:0000305}.
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DR EMBL; AF440757; AAM76996.1; -; mRNA.
DR EMBL; AY515707; AAR99657.1; -; mRNA.
DR EMBL; AL592166; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC101823; AAI01824.1; -; mRNA.
DR CCDS; CCDS514.1; -.
DR RefSeq; NP_695006.1; NM_153274.2.
DR RefSeq; XP_016856511.1; XM_017001022.1.
DR RefSeq; XP_016856512.1; XM_017001023.1.
DR AlphaFoldDB; Q8NFU0; -.
DR SMR; Q8NFU0; -.
DR IntAct; Q8NFU0; 1.
DR MINT; Q8NFU0; -.
DR STRING; 9606.ENSP00000361281; -.
DR TCDB; 1.A.46.1.7; the anion channel-forming bestrophin (bestrophin) family.
DR iPTMnet; Q8NFU0; -.
DR PhosphoSitePlus; Q8NFU0; -.
DR BioMuta; BEST4; -.
DR DMDM; 38503352; -.
DR MassIVE; Q8NFU0; -.
DR PaxDb; Q8NFU0; -.
DR PeptideAtlas; Q8NFU0; -.
DR PRIDE; Q8NFU0; -.
DR ProteomicsDB; 73355; -.
DR Antibodypedia; 18506; 104 antibodies from 22 providers.
DR DNASU; 266675; -.
DR Ensembl; ENST00000372207.4; ENSP00000361281.3; ENSG00000142959.5.
DR GeneID; 266675; -.
DR KEGG; hsa:266675; -.
DR MANE-Select; ENST00000372207.4; ENSP00000361281.3; NM_153274.3; NP_695006.1.
DR UCSC; uc001cmm.4; human.
DR CTD; 266675; -.
DR DisGeNET; 266675; -.
DR GeneCards; BEST4; -.
DR HGNC; HGNC:17106; BEST4.
DR HPA; ENSG00000142959; Group enriched (choroid plexus, fallopian tube, intestine).
DR MIM; 607336; gene.
DR neXtProt; NX_Q8NFU0; -.
DR OpenTargets; ENSG00000142959; -.
DR PharmGKB; PA162377520; -.
DR VEuPathDB; HostDB:ENSG00000142959; -.
DR eggNOG; KOG3547; Eukaryota.
DR GeneTree; ENSGT00940000160852; -.
DR HOGENOM; CLU_018069_0_0_1; -.
DR InParanoid; Q8NFU0; -.
DR OMA; CQLISWP; -.
DR OrthoDB; 279144at2759; -.
DR PhylomeDB; Q8NFU0; -.
DR TreeFam; TF315803; -.
DR PathwayCommons; Q8NFU0; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; Q8NFU0; -.
DR BioGRID-ORCS; 266675; 19 hits in 1065 CRISPR screens.
DR ChiTaRS; BEST4; human.
DR GenomeRNAi; 266675; -.
DR Pharos; Q8NFU0; Tbio.
DR PRO; PR:Q8NFU0; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8NFU0; protein.
DR Bgee; ENSG00000142959; Expressed in mucosa of transverse colon and 94 other tissues.
DR Genevisible; Q8NFU0; HS.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005254; F:chloride channel activity; IEA:UniProtKB-KW.
DR InterPro; IPR000615; Bestrophin.
DR InterPro; IPR021134; Bestrophin/UPF0187.
DR PANTHER; PTHR10736; PTHR10736; 1.
DR Pfam; PF01062; Bestrophin; 1.
PE 2: Evidence at transcript level;
KW Calcium; Cell membrane; Chloride; Chloride channel; Ion channel;
KW Ion transport; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..473
FT /note="Bestrophin-4"
FT /id="PRO_0000143120"
FT TOPO_DOM 1..25
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 26..46
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 47..70
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 92..178
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..228
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 229..249
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..285
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 286..306
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 307..473
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 379..408
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 379..397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 441..464
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 62
FT /note="Y -> C (in dbSNP:rs16832245)"
FT /id="VAR_048411"
FT VARIANT 217
FT /note="Y -> S (in dbSNP:rs16832242)"
FT /id="VAR_048412"
FT VARIANT 331
FT /note="Q -> E (in dbSNP:rs16832241)"
FT /id="VAR_048413"
FT VARIANT 402
FT /note="R -> L (in dbSNP:rs16832239)"
FT /id="VAR_048414"
SQ SEQUENCE 473 AA; 53497 MW; A8538303EE258D65 CRC64;
MTVSYTLKVA EARFGGFSGL LLRWRGSIYK LLYKEFLLFG ALYAVLSITY RLLLTQEQRY
VYAQVARYCN RSADLIPLSF VLGFYVTLVV NRWWSQYTSI PLPDQLMCVI SASVHGVDQR
GRLLRRTLIR YANLASVLVL RSVSTRVLKR FPTMEHVVDA GFMSQEERKK FESLKSDFNK
YWVPCVWFTN LAAQARRDGR IRDDIALCLL LEELNKYRAK CSMLFHYDWI SIPLVYTQVV
TIAVYSFFAL SLVGRQFVEP EAGAAKPQKL LKPGQEPAPA LGDPDMYVPL TTLLQFFFYA
GWLKVAEQII NPFGEDDDDF ETNQLIDRNL QVSLLSVDEM YQNLPPAEKD QYWDEDQPQP
PYTVATAAES LRPSFLGSTF NLRMSDDPEQ SLQVEASPGS GRPAPAAQTP LLGRFLGVGA
PSPAISLRNF GRVRGTPRPP HLLRFRAEEG GDPEAAARIE EESAESGDEA LEP
