BEST3_HUMAN
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 03-AUG-2022, entry version 160.
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 bestrophin family. {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; Q8N1M1; -.
DR PeptideAtlas; Q8N1M1; -.
DR PRIDE; Q8N1M1; -.
DR ProteomicsDB; 28912; -.
DR ProteomicsDB; 71617; -. [Q8N1M1-2]
DR ProteomicsDB; 71618; -. [Q8N1M1-1]
DR ProteomicsDB; 71619; -. [Q8N1M1-4]
DR Antibodypedia; 29432; 303 antibodies from 26 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 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; 279144at2759; -.
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 1057 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 118 other tissues.
DR ExpressionAtlas; Q8N1M1; baseline and differential.
DR Genevisible; Q8N1M1; 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 GO; GO:0043271; P:negative regulation of ion transport; IEA:Ensembl.
DR InterPro; IPR000615; Bestrophin.
DR InterPro; IPR021134; Bestrophin/UPF0187.
DR PANTHER; PTHR10736; PTHR10736; 1.
DR Pfam; PF01062; Bestrophin; 1.
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
