OSTA_HUMAN
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 03-AUG-2022, entry version 124.
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 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; Q86UW1; -.
DR PeptideAtlas; Q86UW1; -.
DR PRIDE; Q86UW1; -.
DR Antibodypedia; 46863; 109 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 CTD; 200931; -.
DR DisGeNET; 200931; -.
DR GeneCards; SLC51A; -.
DR HGNC; HGNC:29955; SLC51A.
DR HPA; ENSG00000163959; Group enriched (intestine, liver).
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; SWFMCHT; -.
DR OrthoDB; 1374406at2759; -.
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 1067 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 106 other tissues.
DR ExpressionAtlas; Q86UW1; baseline and differential.
DR Genevisible; Q86UW1; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of 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; PTHR23423; 1.
DR Pfam; PF03619; Solute_trans_a; 1.
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
