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   24-JAN-2024, entry version 161.
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 anion channel-forming bestrophin (TC 1.A.46)
CC       family. Calcium-sensitive chloride channel subfamily. {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   PDB; 8D1E; EM; 1.78 A; A/B/C/D/E=1-406.
DR   PDB; 8D1F; EM; 1.82 A; A/B/C/D/E=1-406.
DR   PDB; 8D1G; EM; 2.07 A; A/B/C/D/E=1-406.
DR   PDB; 8D1H; EM; 1.94 A; A/B/C/D/E=1-406.
DR   PDBsum; 8D1E; -.
DR   PDBsum; 8D1F; -.
DR   PDBsum; 8D1G; -.
DR   PDBsum; 8D1H; -.
DR   AlphaFoldDB; Q8NFU1; -.
DR   EMDB; EMD-27127; -.
DR   EMDB; EMD-27128; -.
DR   EMDB; EMD-27129; -.
DR   EMDB; EMD-27130; -.
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; 9606-ENSP00000448310; -.
DR   PeptideAtlas; Q8NFU1; -.
DR   ProteomicsDB; 73356; -.
DR   TopDownProteomics; Q8NFU1; -.
DR   Antibodypedia; 26152; 160 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   AGR; HGNC:17107; -.
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; TEARAPY; -.
DR   OrthoDB; 2871698at2759; -.
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 1141 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 cell types or tissues.
DR   ExpressionAtlas; Q8NFU1; baseline and differential.
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-like.
DR   PANTHER; PTHR10736; BESTROPHIN; 1.
DR   PANTHER; PTHR10736:SF1; BESTROPHIN-2; 1.
DR   Pfam; PF01062; Bestrophin; 1.
DR   Genevisible; Q8NFU1; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium; Cell membrane; Chloride; Chloride channel;
KW   Ion channel; 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"
FT   HELIX           7..9
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           16..22
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           28..52
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           56..70
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           75..98
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           104..113
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           119..143
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           145..150
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   STRAND          151..153
FT                   /evidence="ECO:0007829|PDB:8D1F"
FT   HELIX           154..159
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           165..173
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           183..197
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           204..229
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           234..254
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           260..262
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           275..294
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   STRAND          299..301
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           307..323
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   TURN            324..327
FT                   /evidence="ECO:0007829|PDB:8D1F"
FT   TURN            336..339
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   TURN            349..351
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           352..354
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   TURN            363..366
FT                   /evidence="ECO:0007829|PDB:8D1E"
FT   HELIX           372..374
FT                   /evidence="ECO:0007829|PDB:8D1E"
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
//