BEST2_HUMAN
ID BEST2_HUMAN Reviewed; 509 AA.
AC Q8NFU1; Q53YQ8; Q9NXP0;
DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Bestrophin-2;
DE AltName: Full=Vitelliform macular dystrophy 2-like protein 1;
GN Name=BEST2; Synonyms=VMD2L1;
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 MRNA] OF 23-509.
RC TISSUE=Colon;
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 FUNCTION.
RX PubMed=11904445; DOI=10.1073/pnas.052692999;
RA Sun H., Tsunenari T., Yau K.-W., Nathans J.;
RT "The vitelliform macular dystrophy protein defines a new family of chloride
RT channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:4008-4013(2002).
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:11904445, ECO:0000269|PubMed:12907679,
CC ECO:0000269|PubMed:18400985}.
CC -!- INTERACTION:
CC Q8NFU1; P78369: CLDN10; NbExp=3; IntAct=EBI-19947314, EBI-13372810;
CC Q8NFU1; P21964: COMT; NbExp=3; IntAct=EBI-19947314, EBI-372265;
CC Q8NFU1; P49447: CYB561; NbExp=3; IntAct=EBI-19947314, EBI-8646596;
CC Q8NFU1; Q96LL9: DNAJC30; NbExp=3; IntAct=EBI-19947314, EBI-8639143;
CC Q8NFU1; P52803: EFNA5; NbExp=3; IntAct=EBI-19947314, EBI-1753674;
CC Q8NFU1; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-19947314, EBI-12175685;
CC Q8NFU1; O00155: GPR25; NbExp=3; IntAct=EBI-19947314, EBI-10178951;
CC Q8NFU1; Q13021: MALL; NbExp=3; IntAct=EBI-19947314, EBI-750078;
CC Q8NFU1; Q6N075: MFSD5; NbExp=3; IntAct=EBI-19947314, EBI-3920969;
CC Q8NFU1; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-19947314, EBI-8652812;
CC Q8NFU1; Q96AA3: RFT1; NbExp=3; IntAct=EBI-19947314, EBI-6269616;
CC Q8NFU1; Q8N2U9: SLC66A2; NbExp=3; IntAct=EBI-19947314, EBI-3907610;
CC Q8NFU1; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-19947314, EBI-10694905;
CC Q8NFU1; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-19947314, EBI-2852148;
CC Q8NFU1; Q9H1C4: UNC93B1; NbExp=3; IntAct=EBI-19947314, EBI-4401271;
CC Q8NFU1; O75841: UPK1B; NbExp=3; IntAct=EBI-19947314, EBI-12237619;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Mainly confined to the retinal pigment epithelium
CC and colon. {ECO:0000269|PubMed:12032738}.
CC -!- SIMILARITY: Belongs to the bestrophin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA90970.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF440756; AAM76995.1; -; mRNA.
DR EMBL; AY515705; AAR99655.1; -; mRNA.
DR EMBL; AK000139; BAA90970.1; ALT_INIT; mRNA.
DR CCDS; CCDS42506.1; -.
DR RefSeq; NP_060152.2; NM_017682.2.
DR RefSeq; XP_005260020.1; XM_005259963.3.
DR AlphaFoldDB; Q8NFU1; -.
DR SMR; Q8NFU1; -.
DR BioGRID; 120185; 16.
DR IntAct; Q8NFU1; 16.
DR STRING; 9606.ENSP00000448310; -.
DR TCDB; 1.A.46.1.2; the anion channel-forming bestrophin (bestrophin) family.
DR iPTMnet; Q8NFU1; -.
DR PhosphoSitePlus; Q8NFU1; -.
DR BioMuta; BEST2; -.
DR DMDM; 38503353; -.
DR MassIVE; Q8NFU1; -.
DR PaxDb; Q8NFU1; -.
DR PeptideAtlas; Q8NFU1; -.
DR PRIDE; Q8NFU1; -.
DR ProteomicsDB; 73356; -.
DR TopDownProteomics; Q8NFU1; -.
DR Antibodypedia; 26152; 149 antibodies from 24 providers.
DR DNASU; 54831; -.
DR Ensembl; ENST00000042931.1; ENSP00000042931.1; ENSG00000039987.7.
DR Ensembl; ENST00000549706.5; ENSP00000448310.1; ENSG00000039987.7.
DR Ensembl; ENST00000553030.6; ENSP00000447203.1; ENSG00000039987.7.
DR GeneID; 54831; -.
DR KEGG; hsa:54831; -.
DR MANE-Select; ENST00000553030.6; ENSP00000447203.1; NM_017682.3; NP_060152.2.
DR UCSC; uc002mux.4; human.
DR CTD; 54831; -.
DR DisGeNET; 54831; -.
DR GeneCards; BEST2; -.
DR HGNC; HGNC:17107; BEST2.
DR HPA; ENSG00000039987; Group enriched (intestine, skin).
DR MIM; 607335; gene.
DR neXtProt; NX_Q8NFU1; -.
DR OpenTargets; ENSG00000039987; -.
DR PharmGKB; PA162377481; -.
DR VEuPathDB; HostDB:ENSG00000039987; -.
DR eggNOG; KOG3547; Eukaryota.
DR GeneTree; ENSGT00940000161361; -.
DR HOGENOM; CLU_018069_0_0_1; -.
DR InParanoid; Q8NFU1; -.
DR OMA; ISITYFF; -.
DR OrthoDB; 279144at2759; -.
DR PhylomeDB; Q8NFU1; -.
DR TreeFam; TF315803; -.
DR PathwayCommons; Q8NFU1; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; Q8NFU1; -.
DR BioGRID-ORCS; 54831; 12 hits in 1065 CRISPR screens.
DR GeneWiki; BEST2; -.
DR GenomeRNAi; 54831; -.
DR Pharos; Q8NFU1; Tbio.
DR PRO; PR:Q8NFU1; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8NFU1; protein.
DR Bgee; ENSG00000039987; Expressed in mucosa of transverse colon and 101 other tissues.
DR ExpressionAtlas; Q8NFU1; baseline and differential.
DR Genevisible; Q8NFU1; HS.
DR GO; GO:0034707; C:chloride channel complex; ISS:BHF-UCL.
DR GO; GO:0005929; C:cilium; ISS:HGNC-UCL.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005254; F:chloride channel activity; IEA:UniProtKB-KW.
DR GO; GO:0051899; P:membrane depolarization; ISS:HGNC-UCL.
DR GO; GO:0007608; P:sensory perception of smell; ISS:HGNC-UCL.
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 Calcium; Cell membrane; Chloride; Chloride channel; Ion channel;
KW Ion transport; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..509
FT /note="Bestrophin-2"
FT /id="PRO_0000143118"
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..509
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 454..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 456..475
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 388
FT /note="E -> G (in Ref. 2; AAR99655 and 3; BAA90970)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 509 AA; 57139 MW; E557B975BFDC692A CRC64;
MTVTYTARVA NARFGGFSQL LLLWRGSIYK LLWRELLCFL GFYMALSAAY RFVLTEGQKR
YFEKLVIYCD QYASLIPVSF VLGFYVTLVV NRWWSQYLCM PLPDALMCVV AGTVHGRDDR
GRLYRRTLMR YAGLSAVLIL RSVSTAVFKR FPTIDHVVEA GFMTREERKK FENLNSSYNK
YWVPCVWFSN LAAQARREGR IRDNSALKLL LEELNVFRGK CGMLFHYDWI SVPLVYTQVV
TIALYSYFLA CLIGRQFLDP AQGYKDHDLD LCVPIFTLLQ FFFYAGWLKV AEQLINPFGE
DDDDFETNFL IDRNFQVSML AVDEMYDDLA VLEKDLYWDA AEARAPYTAA TVFQLRQPSF
QGSTFDITLA KEDMQFQRLD GLDGPMGEAP GDFLQRLLPA GAGMVAGGPL GRRLSFLLRK
NSCVSEASTG ASCSCAVVPE GAAPECSCGD PLLDPGLPEP EAPPPAGPEP LTLIPGPVEP
FSIVTMPGPR GPAPPWLPSP IGEEEENLA
