ID   BEST3_HUMAN             Reviewed;         668 AA.
AC   Q8N1M1; B5MDI8; F8VVZ2; Q53YQ7; Q8N356; Q8NFT9; Q9BR80;
DT   21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   27-MAR-2024, entry version 168.
DE   RecName: Full=Bestrophin-3;
DE   AltName: Full=Vitelliform macular dystrophy 2-like protein 3;
GN   Name=BEST3; Synonyms=VMD2L3;
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] (ISOFORM 1), 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] (ISOFORM 1), 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 MRNA] (ISOFORM 2).
RC   TISSUE=Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RA   Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA   Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA   Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA   Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA   Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA   Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA   Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA   Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA   Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA   Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA   Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA   Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA   Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA   Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA   Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA   Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA   Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA   David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA   D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA   Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA   Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA   Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA   LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA   Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA   Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA   Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA   Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA   Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA   Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA   Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA   Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA   Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA   Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA   Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA   Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA   Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA   Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA   Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA   Gibbs R.A.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 6).
RC   TISSUE=Lymph;
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).
CC   -!- FUNCTION: Forms calcium-sensitive chloride channels. Permeable to
CC       bicarbonate. {ECO:0000269|PubMed:12907679}.
CC   -!- INTERACTION:
CC       Q8N1M1-5; O15499: GSC2; NbExp=3; IntAct=EBI-20140863, EBI-19954058;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=5;
CC       Name=2;
CC         IsoId=Q8N1M1-2; Sequence=Displayed;
CC       Name=1;
CC         IsoId=Q8N1M1-1; Sequence=VSP_008977, VSP_008978;
CC       Name=4;
CC         IsoId=Q8N1M1-4; Sequence=VSP_008981, VSP_008982, VSP_008983;
CC       Name=5;
CC         IsoId=Q8N1M1-5; Sequence=VSP_046979, VSP_046980;
CC       Name=6;
CC         IsoId=Q8N1M1-6; Sequence=VSP_008981;
CC   -!- TISSUE SPECIFICITY: Present in skeletal muscle and weakly in brain,
CC       spinal cord, bone marrow and retina. {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; AF440758; AAM76997.1; -; mRNA.
DR   EMBL; AY515706; AAR99656.1; -; mRNA.
DR   EMBL; AK096459; BAC04797.1; -; mRNA.
DR   EMBL; AC016153; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC018921; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC025263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC151138; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; BC006440; AAH06440.1; -; mRNA.
DR   CCDS; CCDS41810.1; -. [Q8N1M1-5]
DR   CCDS; CCDS61192.1; -. [Q8N1M1-6]
DR   CCDS; CCDS61193.1; -. [Q8N1M1-1]
DR   CCDS; CCDS73496.1; -. [Q8N1M1-4]
DR   CCDS; CCDS8992.2; -. [Q8N1M1-2]
DR   RefSeq; NP_001269542.1; NM_001282613.1. [Q8N1M1-6]
DR   RefSeq; NP_001269543.1; NM_001282614.1. [Q8N1M1-1]
DR   RefSeq; NP_001269544.1; NM_001282615.1. [Q8N1M1-4]
DR   RefSeq; NP_001269545.1; NM_001282616.1. [Q8N1M1-4]
DR   RefSeq; NP_116124.2; NM_032735.2. [Q8N1M1-2]
DR   RefSeq; NP_689652.2; NM_152439.3. [Q8N1M1-5]
DR   RefSeq; XP_011536263.1; XM_011537961.1. [Q8N1M1-6]
DR   AlphaFoldDB; Q8N1M1; -.
DR   SMR; Q8N1M1; -.
DR   BioGRID; 126854; 1.
DR   IntAct; Q8N1M1; 2.
DR   STRING; 9606.ENSP00000332413; -.
DR   TCDB; 1.A.46.1.8; the anion channel-forming bestrophin (bestrophin) family.
DR   iPTMnet; Q8N1M1; -.
DR   PhosphoSitePlus; Q8N1M1; -.
DR   BioMuta; BEST3; -.
DR   DMDM; 38503351; -.
DR   MassIVE; Q8N1M1; -.
DR   PaxDb; 9606-ENSP00000332413; -.
DR   PeptideAtlas; Q8N1M1; -.
DR   ProteomicsDB; 28912; -.
DR   ProteomicsDB; 6178; -.
DR   ProteomicsDB; 71617; -. [Q8N1M1-2]
DR   ProteomicsDB; 71618; -. [Q8N1M1-1]
DR   ProteomicsDB; 71619; -. [Q8N1M1-4]
DR   Antibodypedia; 29432; 336 antibodies from 27 providers.
DR   DNASU; 144453; -.
DR   Ensembl; ENST00000266661.8; ENSP00000266661.4; ENSG00000127325.19. [Q8N1M1-4]
DR   Ensembl; ENST00000330891.10; ENSP00000332413.5; ENSG00000127325.19. [Q8N1M1-2]
DR   Ensembl; ENST00000331471.8; ENSP00000329064.4; ENSG00000127325.19. [Q8N1M1-1]
DR   Ensembl; ENST00000488961.5; ENSP00000433213.1; ENSG00000127325.19. [Q8N1M1-5]
DR   Ensembl; ENST00000551160.5; ENSP00000449377.1; ENSG00000127325.19. [Q8N1M1-4]
DR   Ensembl; ENST00000553096.5; ENSP00000449548.1; ENSG00000127325.19. [Q8N1M1-6]
DR   GeneID; 144453; -.
DR   KEGG; hsa:144453; -.
DR   MANE-Select; ENST00000330891.10; ENSP00000332413.5; NM_032735.3; NP_116124.2.
DR   UCSC; uc001svd.4; human. [Q8N1M1-2]
DR   AGR; HGNC:17105; -.
DR   CTD; 144453; -.
DR   DisGeNET; 144453; -.
DR   GeneCards; BEST3; -.
DR   HGNC; HGNC:17105; BEST3.
DR   HPA; ENSG00000127325; Group enriched (skeletal muscle, tongue).
DR   MIM; 607337; gene.
DR   neXtProt; NX_Q8N1M1; -.
DR   OpenTargets; ENSG00000127325; -.
DR   PharmGKB; PA162377503; -.
DR   VEuPathDB; HostDB:ENSG00000127325; -.
DR   eggNOG; KOG3547; Eukaryota.
DR   GeneTree; ENSGT00940000157777; -.
DR   HOGENOM; CLU_018069_0_1_1; -.
DR   InParanoid; Q8N1M1; -.
DR   OMA; DWLWNYE; -.
DR   OrthoDB; 2871698at2759; -.
DR   PhylomeDB; Q8N1M1; -.
DR   TreeFam; TF315803; -.
DR   PathwayCommons; Q8N1M1; -.
DR   Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR   SignaLink; Q8N1M1; -.
DR   BioGRID-ORCS; 144453; 10 hits in 1129 CRISPR screens.
DR   ChiTaRS; BEST3; human.
DR   GenomeRNAi; 144453; -.
DR   Pharos; Q8N1M1; Tbio.
DR   PRO; PR:Q8N1M1; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q8N1M1; Protein.
DR   Bgee; ENSG00000127325; Expressed in tibialis anterior and 119 other cell types or tissues.
DR   ExpressionAtlas; Q8N1M1; baseline and differential.
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   GO; GO:0043271; P:negative regulation of monoatomic ion transport; IEA:Ensembl.
DR   InterPro; IPR000615; Bestrophin.
DR   InterPro; IPR021134; Bestrophin-like.
DR   PANTHER; PTHR10736; BESTROPHIN; 1.
DR   PANTHER; PTHR10736:SF0; BESTROPHIN-3; 1.
DR   Pfam; PF01062; Bestrophin; 1.
DR   Genevisible; Q8N1M1; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calcium; Cell membrane; Chloride; Chloride channel;
KW   Ion channel; Ion transport; Membrane; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..668
FT                   /note="Bestrophin-3"
FT                   /id="PRO_0000143121"
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..270
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        271..291
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        292..668
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          400..454
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          473..493
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          532..570
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        400..416
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        532..550
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..162
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_046979"
FT   VAR_SEQ         1..106
FT                   /note="Missing (in isoform 4 and isoform 6)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_008981"
FT   VAR_SEQ         161..178
FT                   /note="GFMTTDERKLFNHLKSPH -> ERTGMKPILPSSFEMQSF (in isoform
FT                   4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_008982"
FT   VAR_SEQ         179..668
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_008983"
FT   VAR_SEQ         239..289
FT                   /note="Missing (in isoform 5)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_046980"
FT   VAR_SEQ         368..398
FT                   /note="LSGSDFPDEEWLWDYEKHGHRHSMIRRVKRF -> KQMPKNEWKMEDIKIPL
FT                   PQPQFQCAKSDPGG (in isoform 1)"
FT                   /evidence="ECO:0000303|PubMed:12032738,
FT                   ECO:0000303|PubMed:12907679"
FT                   /id="VSP_008977"
FT   VAR_SEQ         399..668
FT                   /note="Missing (in isoform 1)"
FT                   /evidence="ECO:0000303|PubMed:12032738,
FT                   ECO:0000303|PubMed:12907679"
FT                   /id="VSP_008978"
FT   VARIANT         43
FT                   /note="Y -> H (in dbSNP:rs1025016)"
FT                   /id="VAR_048409"
FT   VARIANT         622
FT                   /note="E -> G (in dbSNP:rs17106884)"
FT                   /id="VAR_048410"
SQ   SEQUENCE   668 AA;  76107 MW;  FDCBD7154C402EA2 CRC64;
     MTVTYSSKVA NATFFGFHRL LLKWRGSIYK LLYREFIVFA VLYTAISLVY RLLLTGVQKR
     YFEKLSIYCD RYAEQIPVTF VLGFYVTLVV NRWWNQFVNL PWPDRLMFLI SSSVHGSDEH
     GRLLRRTLMR YVNLTSLLIF RSVSTAVYKR FPTMDHVVEA GFMTTDERKL FNHLKSPHLK
     YWVPFIWFGN LATKARNEGR IRDSVDLQSL MTEMNRYRSW CSLLFGYDWV GIPLVYTQVV
     TLAVYTFFFA CLIGRQFLDP TKGYAGHDLD LYIPIFTLLQ FFFYAGWLKV AEQLINPFGE
     DDDDFETNWC IDRNLQVSLL AVDEMHMSLP KMKKDIYWDD SAARPPYTLA AADYCIPSFL
     GSTVQMGLSG SDFPDEEWLW DYEKHGHRHS MIRRVKRFLS AHEHPSSPRR RSYRRQTSDS
     SMFLPRDDLS PARDLLDVPS RNPPRASPTW KKSCFPEGSP TLHFSMGELS TIRETSQTST
     LQSLTPQSSV RTSPIKMPLV PEVLITAAEA PVPTSGGYHH DSATSILSSE FTGVQPSKTE
     QQQGPMGSIL SPSEKETPPG GPSPQTVSAS AEENIFNCEE DPGDTFLKRW SLPGFLGSSH
     TSLGNLSPDP MSSQPALLID TETSSEISGI NIVAGSRVSS DMLYLMENLD TKETDIIELN
     KETEESPK
//