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   27-MAR-2024, entry version 152.
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 anion channel-forming bestrophin (TC 1.A.46)
CC       family. Calcium-sensitive chloride channel subfamily. {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   BioGRID; 129314; 1.
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; 9606-ENSP00000361281; -.
DR   PeptideAtlas; Q8NFU0; -.
DR   ProteomicsDB; 73355; -.
DR   Antibodypedia; 18506; 122 antibodies from 23 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   AGR; HGNC:17106; -.
DR   CTD; 266675; -.
DR   DisGeNET; 266675; -.
DR   GeneCards; BEST4; -.
DR   HGNC; HGNC:17106; BEST4.
DR   HPA; ENSG00000142959; Tissue enhanced (choroid plexus, 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; 2871698at2759; -.
DR   PhylomeDB; Q8NFU0; -.
DR   TreeFam; TF315803; -.
DR   PathwayCommons; Q8NFU0; -.
DR   Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR   SignaLink; Q8NFU0; -.
DR   BioGRID-ORCS; 266675; 31 hits in 1141 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 95 other cell types or tissues.
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-like.
DR   PANTHER; PTHR10736; BESTROPHIN; 1.
DR   PANTHER; PTHR10736:SF66; BESTROPHIN-4; 1.
DR   Pfam; PF01062; Bestrophin; 1.
DR   Genevisible; Q8NFU0; HS.
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
//