ID   OSTA_HUMAN              Reviewed;         340 AA.
AC   Q86UW1; Q6ZMC7;
DT   29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   24-JAN-2024, entry version 132.
DE   RecName: Full=Organic solute transporter subunit alpha {ECO:0000303|PubMed:16317684};
DE            Short=OST-alpha {ECO:0000303|PubMed:16317684};
DE   AltName: Full=Solute carrier family 51 subunit alpha;
GN   Name=SLC51A; Synonyms=OSTA;
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Liver;
RX   PubMed=12719432; DOI=10.1074/jbc.m301106200;
RA   Seward D.J., Koh A.S., Boyer J.L., Ballatori N.;
RT   "Functional complementation between a novel mammalian polygenic transport
RT   complex and an evolutionarily ancient organic solute transporter, OSTalpha-
RT   OSTbeta.";
RL   J. Biol. Chem. 278:27473-27482(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-202.
RC   TISSUE=Small intestine;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND TRANSPORT ACTIVITY.
RX   PubMed=16317684; DOI=10.1002/hep.20961;
RA   Ballatori N., Christian W.V., Lee J.Y., Dawson P.A., Soroka C.J.,
RA   Boyer J.L., Madejczyk M.S., Li N.;
RT   "OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in
RT   human intestinal, renal, and biliary epithelia.";
RL   Hepatology 42:1270-1279(2005).
RN   [5]
RP   INDUCTION BY NR1H4.
RX   PubMed=16269519; DOI=10.1152/ajpgi.00430.2005;
RA   Landrier J.-F., Eloranta J.J., Vavricka S.R., Kullak-Ublick G.A.;
RT   "The nuclear receptor for bile acids, FXR, transactivates human organic
RT   solute transporter-alpha and -beta genes.";
RL   Am. J. Physiol. 290:G476-G485(2006).
RN   [6]
RP   INDUCTION BY NR1H4.
RX   PubMed=16251721; DOI=10.1194/jlr.m500417-jlr200;
RA   Lee H., Zhang Y., Lee F.Y., Nelson S.F., Gonzalez F.J., Edwards P.A.;
RT   "FXR regulates organic solute transporters alpha and beta in the adrenal
RT   gland, kidney, and intestine.";
RL   J. Lipid Res. 47:201-214(2006).
RN   [7]
RP   VARIANT PFIC6 186-GLN--ALA-340 DEL, AND INVOLVEMENT IN PFIC6.
RX   PubMed=31863603; DOI=10.1002/hep.31087;
RA   Gao E., Cheema H., Waheed N., Mushtaq I., Erden N., Nelson-Williams C.,
RA   Jain D., Soroka C.J., Boyer J.L., Khalil Y., Clayton P.T., Mistry P.K.,
RA   Lifton R.P., Vilarinho S.;
RT   "Organic solute transporter alpha deficiency: A disorder with cholestasis,
RT   liver fibrosis, and congenital diarrhea.";
RL   Hepatology 71:1879-1882(2020).
CC   -!- FUNCTION: Essential component of the Ost-alpha/Ost-beta complex, a
CC       heterodimer that acts as the intestinal basolateral transporter
CC       responsible for bile acid export from enterocytes into portal blood
CC       (PubMed:16317684). Efficiently transports the major species of bile
CC       acids (taurocholate) (PubMed:16317684). Taurine conjugates are
CC       transported more efficiently across the basolateral membrane than
CC       glycine-conjugated bile acids (By similarity). Can also transport
CC       steroids such as estrone 3-sulfate and dehydroepiandrosterone 3-
CC       sulfate, therefore playing a role in the enterohepatic circulation of
CC       sterols (PubMed:16317684). Able to transport eicosanoids such as
CC       prostaglandin E2 (By similarity). {ECO:0000250|UniProtKB:Q8R000,
CC       ECO:0000250|UniProtKB:Q90YM5, ECO:0000269|PubMed:16317684}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=taurocholate(out) = taurocholate(in); Xref=Rhea:RHEA:71703,
CC         ChEBI:CHEBI:36257; Evidence={ECO:0000269|PubMed:16317684};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=estrone 3-sulfate(out) = estrone 3-sulfate(in);
CC         Xref=Rhea:RHEA:71835, ChEBI:CHEBI:60050;
CC         Evidence={ECO:0000269|PubMed:16317684};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dehydroepiandrosterone 3-sulfate(out) = dehydroepiandrosterone
CC         3-sulfate(in); Xref=Rhea:RHEA:71839, ChEBI:CHEBI:57905;
CC         Evidence={ECO:0000269|PubMed:16317684};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=tauroursodeoxycholate(out) = tauroursodeoxycholate(in);
CC         Xref=Rhea:RHEA:71843, ChEBI:CHEBI:132028;
CC         Evidence={ECO:0000250|UniProtKB:Q8R000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glycoursodeoxycholate(out) = glycoursodeoxycholate(in);
CC         Xref=Rhea:RHEA:71847, ChEBI:CHEBI:132030;
CC         Evidence={ECO:0000250|UniProtKB:Q8R000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glycocholate(out) = glycocholate(in); Xref=Rhea:RHEA:71851,
CC         ChEBI:CHEBI:29746; Evidence={ECO:0000250|UniProtKB:Q8R000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=taurochenodeoxycholate(out) = taurochenodeoxycholate(in);
CC         Xref=Rhea:RHEA:71855, ChEBI:CHEBI:9407;
CC         Evidence={ECO:0000250|UniProtKB:Q8R000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glycochenodeoxycholate(out) = glycochenodeoxycholate(in);
CC         Xref=Rhea:RHEA:71859, ChEBI:CHEBI:36252;
CC         Evidence={ECO:0000250|UniProtKB:Q8R000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=taurodeoxycholate(out) = taurodeoxycholate(in);
CC         Xref=Rhea:RHEA:71863, ChEBI:CHEBI:36261;
CC         Evidence={ECO:0000250|UniProtKB:Q8R000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glycodeoxycholate(out) = glycodeoxycholate(in);
CC         Xref=Rhea:RHEA:71867, ChEBI:CHEBI:82982;
CC         Evidence={ECO:0000250|UniProtKB:Q8R000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=prostaglandin E2(out) = prostaglandin E2(in);
CC         Xref=Rhea:RHEA:50984, ChEBI:CHEBI:606564;
CC         Evidence={ECO:0000250|UniProtKB:Q90YM5};
CC   -!- SUBUNIT: Interacts with SLC51B. The Ost-alpha/Ost-beta complex is a
CC       heterodimer composed of alpha (SLC51A) and beta (SLC51B) subunit (By
CC       similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q86UW1; P54253: ATXN1; NbExp=7; IntAct=EBI-945738, EBI-930964;
CC       Q86UW1; Q96LL9: DNAJC30; NbExp=3; IntAct=EBI-945738, EBI-8639143;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16317684};
CC       Multi-pass membrane protein. Endoplasmic reticulum membrane
CC       {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
CC       Note=Transported from the endoplasmic reticulum to the plasma membrane
CC       upon interacting with SLC51B (By similarity). Mainly restricted to the
CC       lateral and basal membranes of ileal enterocytes. {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Widely expressed with a high expression in ileum.
CC       Expressed in testis, colon, liver, small intestine, kidney, ovary and
CC       adrenal gland; and at low levels in heart, lung, brain, pituitary,
CC       thyroid gland, uterus, prostate, mammary gland and fat.
CC       {ECO:0000269|PubMed:12719432, ECO:0000269|PubMed:16317684}.
CC   -!- INDUCTION: Positively regulated via NR1H4/FXR in adrenal gland, kidney
CC       and intestine. {ECO:0000269|PubMed:16251721,
CC       ECO:0000269|PubMed:16269519}.
CC   -!- DISEASE: Cholestasis, progressive familial intrahepatic, 6 (PFIC6)
CC       [MIM:619484]: An autosomal recessive form of progressive cholestasis, a
CC       disorder characterized by early onset of cholestasis that progresses to
CC       hepatic fibrosis, cirrhosis, and end-stage liver disease. PFIC6
CC       patients have elevated liver transaminases and congenital diarrhea.
CC       {ECO:0000269|PubMed:31863603}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the OST-alpha family. {ECO:0000305}.
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DR   EMBL; AY194243; AAP23993.1; -; mRNA.
DR   EMBL; AK172837; BAD18802.1; -; mRNA.
DR   EMBL; CH471191; EAW53665.1; -; Genomic_DNA.
DR   CCDS; CCDS3314.1; -.
DR   RefSeq; NP_689885.4; NM_152672.5.
DR   AlphaFoldDB; Q86UW1; -.
DR   BioGRID; 128357; 7.
DR   IntAct; Q86UW1; 7.
DR   STRING; 9606.ENSP00000296327; -.
DR   ChEMBL; CHEMBL2073724; -.
DR   DrugBank; DB00286; Conjugated estrogens.
DR   DrugBank; DB00390; Digoxin.
DR   DrugBank; DB00917; Dinoprostone.
DR   DrugBank; DB04348; Taurocholic acid.
DR   TCDB; 2.A.82.1.2; the organic solute transporter (ost) family.
DR   GlyCosmos; Q86UW1; 2 sites, 1 glycan.
DR   GlyGen; Q86UW1; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q86UW1; -.
DR   PhosphoSitePlus; Q86UW1; -.
DR   BioMuta; SLC51A; -.
DR   jPOST; Q86UW1; -.
DR   MassIVE; Q86UW1; -.
DR   PaxDb; 9606-ENSP00000296327; -.
DR   PeptideAtlas; Q86UW1; -.
DR   Antibodypedia; 46863; 122 antibodies from 18 providers.
DR   DNASU; 200931; -.
DR   Ensembl; ENST00000296327.10; ENSP00000296327.5; ENSG00000163959.10.
DR   GeneID; 200931; -.
DR   KEGG; hsa:200931; -.
DR   MANE-Select; ENST00000296327.10; ENSP00000296327.5; NM_152672.6; NP_689885.4.
DR   UCSC; uc003fwd.4; human.
DR   AGR; HGNC:29955; -.
DR   CTD; 200931; -.
DR   DisGeNET; 200931; -.
DR   GeneCards; SLC51A; -.
DR   HGNC; HGNC:29955; SLC51A.
DR   HPA; ENSG00000163959; Group enriched (intestine, liver).
DR   MalaCards; SLC51A; -.
DR   MIM; 612084; gene.
DR   MIM; 619484; phenotype.
DR   neXtProt; NX_Q86UW1; -.
DR   OpenTargets; ENSG00000163959; -.
DR   VEuPathDB; HostDB:ENSG00000163959; -.
DR   eggNOG; ENOG502R3BX; Eukaryota.
DR   GeneTree; ENSGT00940000160780; -.
DR   HOGENOM; CLU_054316_0_0_1; -.
DR   InParanoid; Q86UW1; -.
DR   OMA; CLPMVIP; -.
DR   OrthoDB; 5355208at2759; -.
DR   PhylomeDB; Q86UW1; -.
DR   PathwayCommons; Q86UW1; -.
DR   Reactome; R-HSA-159418; Recycling of bile acids and salts.
DR   SignaLink; Q86UW1; -.
DR   BioGRID-ORCS; 200931; 15 hits in 1145 CRISPR screens.
DR   GeneWiki; OSTalpha; -.
DR   GenomeRNAi; 200931; -.
DR   Pharos; Q86UW1; Tbio.
DR   PRO; PR:Q86UW1; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q86UW1; Protein.
DR   Bgee; ENSG00000163959; Expressed in ileal mucosa and 108 other cell types or tissues.
DR   ExpressionAtlas; Q86UW1; baseline and differential.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR   GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR   GO; GO:0015125; F:bile acid transmembrane transporter activity; IEA:Ensembl.
DR   GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0015721; P:bile acid and bile salt transport; ISS:UniProtKB.
DR   GO; GO:0032782; P:bile acid secretion; IPI:UniProtKB.
DR   InterPro; IPR005178; Ostalpha/TMEM184C.
DR   PANTHER; PTHR23423:SF11; ORGANIC SOLUTE TRANSPORTER SUBUNIT ALPHA; 1.
DR   PANTHER; PTHR23423; ORGANIC SOLUTE TRANSPORTER-RELATED; 1.
DR   Pfam; PF03619; Solute_trans_a; 1.
DR   SMART; SM01417; Solute_trans_a; 1.
DR   Genevisible; Q86UW1; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Disease variant; Endoplasmic reticulum;
KW   Intrahepatic cholestasis; Lipid transport; Membrane; Phosphoprotein;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..340
FT                   /note="Organic solute transporter subunit alpha"
FT                   /id="PRO_0000331543"
FT   TOPO_DOM        1..48
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        49..69
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        70..87
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        88..108
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        109..118
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        119..139
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        140..181
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        182..202
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        203..218
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        219..239
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        240..255
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        256..276
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        277..294
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        295..317
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        318..340
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         330
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8R000"
FT   VARIANT         186..340
FT                   /note="Missing (in PFIC6; loss of expression in the colon
FT                   of an homozygous patient)"
FT                   /evidence="ECO:0000269|PubMed:31863603"
FT                   /id="VAR_086189"
FT   VARIANT         202
FT                   /note="V -> I (in dbSNP:rs939885)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_042895"
SQ   SEQUENCE   340 AA;  37735 MW;  D6725C479A7DF114 CRC64;
     MEPGRTQIKL DPRYTADLLE VLKTNYGIPS ACFSQPPTAA QLLRALGPVE LALTSILTLL
     ALGSIAIFLE DAVYLYKNTL CPIKRRTLLW KSSAPTVVSV LCCFGLWIPR SLVLVEMTIT
     SFYAVCFYLL MLVMVEGFGG KEAVLRTLRD TPMMVHTGPC CCCCPCCPRL LLTRKKLQLL
     MLGPFQYAFL KITLTLVGLF LVPDGIYDPA DISEGSTALW INTFLGVSTL LALWTLGIIS
     RQARLHLGEQ NMGAKFALFQ VLLILTALQP SIFSVLANGG QIACSPPYSS KTRSQVMNCH
     LLILETFLMT VLTRMYYRRK DHKVGYETFS SPDLDLNLKA
//