OSTA_MOUSE
ID OSTA_MOUSE Reviewed; 340 AA.
AC Q8R000;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Organic solute transporter subunit alpha {ECO:0000303|PubMed:22535958};
DE Short=OST-alpha {ECO:0000303|PubMed:17650074};
DE AltName: Full=Solute carrier family 51 subunit alpha;
GN Name=Slc51a; Synonyms=Osta;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon, and Kidney;
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).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=15563450; DOI=10.1074/jbc.m412752200;
RA Dawson P.A., Hubbert M., Haywood J., Craddock A.L., Zerangue N.,
RA Christian W.V., Ballatori N.;
RT "The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta,
RT is an ileal basolateral bile acid transporter.";
RL J. Biol. Chem. 280:6960-6968(2005).
RN [4]
RP FUNCTION, 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=16357058; DOI=10.1152/ajpgi.00479.2005;
RA Frankenberg T., Rao A., Chen F., Haywood J., Shneider B.L., Dawson P.A.;
RT "Regulation of the mouse organic solute transporter alpha-beta, Ostalpha-
RT Ostbeta, by bile acids.";
RL Am. J. Physiol. 290:G912-G922(2006).
RN [6]
RP INDUCTION.
RX PubMed=16628672; DOI=10.1002/hep.21158;
RA Mennone A., Soroka C.J., Cai S.Y., Harry K., Adachi M., Hagey L.,
RA Schuetz J.D., Boyer J.L.;
RT "Mrp4-/- mice have an impaired cytoprotective response in obstructive
RT cholestasis.";
RL Hepatology 43:1013-1021(2006).
RN [7]
RP IDENTIFICATION OF THE OST-ALPHA/OST-BETA COMPLEX, FUNCTION, SUBCELLULAR
RP LOCATION, TOPOLOGY, INTERACTION WITH SLC51B, AND TRANSPORT ACTIVITY.
RX PubMed=17650074; DOI=10.1042/bj20070716;
RA Li N., Cui Z., Fang F., Lee J.Y., Ballatori N.;
RT "Heterodimerization, trafficking and membrane topology of the two proteins,
RT Ost alpha and Ost beta, that constitute the organic solute and steroid
RT transporter.";
RL Biochem. J. 407:363-372(2007).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TRANSPORT ACTIVITY.
RX PubMed=18292224; DOI=10.1073/pnas.0712328105;
RA Rao A., Haywood J., Craddock A.L., Belinsky M.G., Kruh G.D., Dawson P.A.;
RT "The organic solute transporter alpha-beta, Ostalpha-Ostbeta, is essential
RT for intestinal bile acid transport and homeostasis.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3891-3896(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-330, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION OF THE OST-ALPHA/OST-BETA COMPLEX IN BILE TRANSPORT, SUBCELLULAR
RP LOCATION, AND TRANSPORT ACTIVITY.
RX PubMed=22535958; DOI=10.1074/jbc.m112.352245;
RA Christian W.V., Li N., Hinkle P.M., Ballatori N.;
RT "beta-Subunit of the Ostalpha-Ostbeta organic solute transporter is
RT required not only for heterodimerization and trafficking but also for
RT function.";
RL J. Biol. Chem. 287:21233-21243(2012).
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:15563450, PubMed:16317684, PubMed:17650074, PubMed:18292224,
CC PubMed:22535958). Efficiently transports the major species of bile
CC acids (taurocholate) (PubMed:16317684, PubMed:17650074,
CC PubMed:18292224, PubMed:22535958). Taurine conjugates are transported
CC more efficiently across the basolateral membrane than glycine-
CC conjugated bile acids (PubMed:16317684). Can also transport steroids
CC such as estrone 3-sulfate and dehydroepiandrosterone 3-sulfate,
CC therefore playing a role in the enterohepatic circulation of sterols
CC (By similarity). Able to transport eicosanoids such as prostaglandin E2
CC (By similarity). {ECO:0000250|UniProtKB:Q86UW1,
CC ECO:0000250|UniProtKB:Q90YM5, ECO:0000269|PubMed:15563450,
CC ECO:0000269|PubMed:16317684, ECO:0000269|PubMed:17650074,
CC ECO:0000269|PubMed:18292224, ECO:0000269|PubMed:22535958}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurocholate(out) = taurocholate(in); Xref=Rhea:RHEA:71703,
CC ChEBI:CHEBI:36257; Evidence={ECO:0000269|PubMed:16317684,
CC ECO:0000269|PubMed:17650074, ECO:0000269|PubMed:22535958,
CC ECO:0000305|PubMed:18292224};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=tauroursodeoxycholate(out) = tauroursodeoxycholate(in);
CC Xref=Rhea:RHEA:71843, ChEBI:CHEBI:132028;
CC Evidence={ECO:0000269|PubMed:16317684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycoursodeoxycholate(out) = glycoursodeoxycholate(in);
CC Xref=Rhea:RHEA:71847, ChEBI:CHEBI:132030;
CC Evidence={ECO:0000269|PubMed:16317684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycocholate(out) = glycocholate(in); Xref=Rhea:RHEA:71851,
CC ChEBI:CHEBI:29746; Evidence={ECO:0000269|PubMed:16317684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurochenodeoxycholate(out) = taurochenodeoxycholate(in);
CC Xref=Rhea:RHEA:71855, ChEBI:CHEBI:9407;
CC Evidence={ECO:0000269|PubMed:16317684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycochenodeoxycholate(out) = glycochenodeoxycholate(in);
CC Xref=Rhea:RHEA:71859, ChEBI:CHEBI:36252;
CC Evidence={ECO:0000269|PubMed:16317684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurodeoxycholate(out) = taurodeoxycholate(in);
CC Xref=Rhea:RHEA:71863, ChEBI:CHEBI:36261;
CC Evidence={ECO:0000269|PubMed:16317684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycodeoxycholate(out) = glycodeoxycholate(in);
CC Xref=Rhea:RHEA:71867, ChEBI:CHEBI:82982;
CC Evidence={ECO:0000269|PubMed:16317684};
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 -!- CATALYTIC ACTIVITY:
CC Reaction=estrone 3-sulfate(out) = estrone 3-sulfate(in);
CC Xref=Rhea:RHEA:71835, ChEBI:CHEBI:60050;
CC Evidence={ECO:0000250|UniProtKB:Q86UW1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dehydroepiandrosterone 3-sulfate(out) = dehydroepiandrosterone
CC 3-sulfate(in); Xref=Rhea:RHEA:71839, ChEBI:CHEBI:57905;
CC Evidence={ECO:0000250|UniProtKB:Q86UW1};
CC -!- SUBUNIT: Interacts with SLC51B. The Ost-alpha/Ost-beta complex is a
CC heterodimer composed of alpha (SLC51A) and beta (SLC51B) subunit.
CC {ECO:0000269|PubMed:17650074}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Endoplasmic reticulum membrane; Multi-pass membrane protein.
CC Note=Mainly restricted to the lateral and basal membranes of ileal
CC enterocytes. Transported from the endoplasmic reticulum to the plasma
CC membrane upon interacting with SLC51B. {ECO:0000269|PubMed:17650074}.
CC -!- TISSUE SPECIFICITY: Present at high levels in ileum. In ileum, it is
CC restricted to the apical domain on the mature villus enterocytes with
CC little detectable expression in the goblet cells or crypt enterocytes
CC (at protein level). Expressed in kidney but not in heart, brain, liver,
CC spleen, embryo, lung, thymus, ovary nor testis.
CC {ECO:0000269|PubMed:15563450, ECO:0000269|PubMed:16317684}.
CC -!- INDUCTION: Positively regulated via the bile acid-activated nuclear
CC receptor farnesoid X receptor (NR1H4/FXR). Up-regulated in mice lacking
CC Mrp4, but it is unable to compensate for the absence of Mrp4.
CC {ECO:0000269|PubMed:16357058, ECO:0000269|PubMed:16628672}.
CC -!- PTM: N-glycosylated. {ECO:0000305|PubMed:15563450}.
CC -!- DISRUPTION PHENOTYPE: Mice are physically indistinguishable from wild-
CC type mice but display strongly reduced transileal transport of
CC taurocholate. Moreover, the bile acid pool size is significantly
CC reduced, but fecal bile acid excretion is not elevated.
CC {ECO:0000269|PubMed:18292224}.
CC -!- SIMILARITY: Belongs to the OST-alpha family. {ECO:0000305}.
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DR EMBL; AK052725; BAC35116.1; -; mRNA.
DR EMBL; AK147155; BAE27722.1; -; mRNA.
DR EMBL; BC024441; AAH24441.1; -; mRNA.
DR EMBL; BC025912; AAH25912.1; -; mRNA.
DR EMBL; BC031178; AAH31178.1; -; mRNA.
DR CCDS; CCDS28121.1; -.
DR RefSeq; NP_666044.1; NM_145932.3.
DR AlphaFoldDB; Q8R000; -.
DR STRING; 10090.ENSMUSP00000046286; -.
DR ChEMBL; CHEMBL2073723; -.
DR GlyGen; Q8R000; 1 site.
DR iPTMnet; Q8R000; -.
DR PhosphoSitePlus; Q8R000; -.
DR PaxDb; Q8R000; -.
DR PRIDE; Q8R000; -.
DR ProteomicsDB; 294080; -.
DR Antibodypedia; 46863; 109 antibodies from 18 providers.
DR DNASU; 106407; -.
DR Ensembl; ENSMUST00000042042; ENSMUSP00000046286; ENSMUSG00000035699.
DR GeneID; 106407; -.
DR KEGG; mmu:106407; -.
DR UCSC; uc007yyx.1; mouse.
DR CTD; 200931; -.
DR MGI; MGI:2146634; Slc51a.
DR VEuPathDB; HostDB:ENSMUSG00000035699; -.
DR eggNOG; ENOG502R3BX; Eukaryota.
DR GeneTree; ENSGT00940000160780; -.
DR HOGENOM; CLU_054316_0_0_1; -.
DR InParanoid; Q8R000; -.
DR OMA; SWFMCHT; -.
DR OrthoDB; 1374406at2759; -.
DR PhylomeDB; Q8R000; -.
DR TreeFam; TF316050; -.
DR Reactome; R-MMU-159418; Recycling of bile acids and salts.
DR BioGRID-ORCS; 106407; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q8R000; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q8R000; protein.
DR Bgee; ENSMUSG00000035699; Expressed in ileum and 43 other tissues.
DR ExpressionAtlas; Q8R000; baseline and differential.
DR Genevisible; Q8R000; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0015125; F:bile acid transmembrane transporter activity; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; IPI:MGI.
DR GO; GO:0015721; P:bile acid and bile salt transport; IDA:UniProtKB.
DR GO; GO:0032782; P:bile acid secretion; ISO:MGI.
DR GO; GO:0071702; P:organic substance transport; IPI:MGI.
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; Endoplasmic reticulum; Glycoprotein; Lipid transport;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..340
FT /note="Organic solute transporter subunit alpha"
FT /id="PRO_0000331544"
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..114
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..135
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 136..181
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 203..219
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 220..240
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 241..255
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..297
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..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:0007744|PubMed:21183079"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 340 AA; 37759 MW; 5A072346AB5402F7 CRC64;
MEPGRTHIKL DPRYTAELLE LLETNYSISP ACFSHPPTAA QLLRALGPVD IALTIILTFL
TTGSVAIFLE DAVYLYKNTL CPIKKRTLIW SSSAPTVVSV FCCFGLWIPR ALTLVEMAIT
SFYAVCFYLL MMVMVEGFGG KKAVLRTLKD TPMRVHTGPC CCCCPCCPPL ILTRKKLQLL
LLGPFQYAFF KITLSIVGLF LIPDGIYDPG EISEKSAALW INNLLAVSTL LALWSLAILF
RQAKMHLGEQ NMGSKFALFQ VLVILTALQP AIFSILANSG QIACSPPYSS KIRSQVMNCH
MLILETFLMT VLTRMYYRRK DDKVGYEACS LPDLDSALKA
