NTCP2_HUMAN
ID NTCP2_HUMAN Reviewed; 348 AA.
AC Q12908; A1L4F4; Q13839;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Ileal sodium/bile acid cotransporter;
DE AltName: Full=Apical sodium-dependent bile acid transporter;
DE Short=ASBT;
DE AltName: Full=Ileal Na(+)/bile acid cotransporter;
DE AltName: Full=Ileal sodium-dependent bile acid transporter;
DE Short=IBAT;
DE Short=ISBT;
DE AltName: Full=Na(+)-dependent ileal bile acid transporter;
DE AltName: Full=Sodium/taurocholate cotransporting polypeptide, ileal;
DE AltName: Full=Solute carrier family 10 member 2;
GN Name=SLC10A2; Synonyms=ASBT, ISBT, NTCP2;
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 VARIANTS ALA-171 AND CD SER-290.
RC TISSUE=Ileum;
RX PubMed=7592981; DOI=10.1074/jbc.270.45.27228;
RA Wong M.H., Oelkers P., Dawson P.A.;
RT "Identification of a mutation in the ileal sodium-dependent bile acid
RT transporter gene that abolishes transport activity.";
RL J. Biol. Chem. 270:27228-27234(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PBAM PRO-243 AND MET-262, AND
RP VARIANT ALA-171.
RX PubMed=9109432; DOI=10.1172/jci119355;
RA Oelkers P., Kirby L.C., Heubi J.E., Dawson P.A.;
RT "Primary bile acid malabsorption caused by mutations in the ileal sodium-
RT dependent bile acid transporter gene (SLC10A2).";
RL J. Clin. Invest. 99:1880-1887(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-171.
RX PubMed=12364586; DOI=10.1073/pnas.182412499;
RA Chumakov I., Blumenfeld M., Guerassimenko O., Cavarec L., Palicio M.,
RA Abderrahim H., Bougueleret L., Barry C., Tanaka H., La Rosa P., Puech A.,
RA Tahri N., Cohen-Akenine A., Delabrosse S., Lissarrague S., Picard F.-P.,
RA Maurice K., Essioux L., Millasseau P., Grel P., Debailleul V., Simon A.-M.,
RA Caterina D., Dufaure I., Malekzadeh K., Belova M., Luan J.-J., Bouillot M.,
RA Sambucy J.-L., Primas G., Saumier M., Boubkiri N., Martin-Saumier S.,
RA Nasroune M., Peixoto H., Delaye A., Pinchot V., Bastucci M., Guillou S.,
RA Chevillon M., Sainz-Fuertes R., Meguenni S., Aurich-Costa J., Cherif D.,
RA Gimalac A., Van Duijn C., Gauvreau D., Ouellette G., Fortier I.,
RA Raelson J., Sherbatich T., Riazanskay N., Rogaev E., Raeymaekers P.,
RA Aerssens J., Konings F., Luyten W., Macciardi F., Sham P.C., Straub R.E.,
RA Weinberger D.R., Cohen N., Cohen D.;
RT "Genetic and physiological data implicating the new human gene G72 and the
RT gene for D-amino acid oxidase in schizophrenia.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13675-13680(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-171.
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-171.
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
RC TISSUE=Blood;
RA Stengelin S., Becker W., Maier M., Rosenberger J., Kramer W.;
RT "Human ileal sodium-dependent bile acid transporter gene (promoter, exon 1
RT and intron 1).";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP GLYCOSYLATION AT ASN-10, MUTAGENESIS OF ASN-10 AND ASN-328, AND TOPOLOGY.
RX PubMed=15350125; DOI=10.1021/bi049270a;
RA Zhang E.Y., Phelps M.A., Banerjee A., Khantwal C.M., Chang C., Helsper F.,
RA Swaan P.W.;
RT "Topology scanning and putative three-dimensional structure of the
RT extracellular binding domains of the apical sodium-dependent bile acid
RT transporter (SLC10A2).";
RL Biochemistry 43:11380-11392(2004).
RN [9]
RP VARIANTS ILE-98; ILE-159 AND ALA-171.
RX PubMed=11742882; DOI=10.1161/hq1201.100262;
RA Love M.W., Craddock A.L., Angelin B., Brunzell J.D., Duane W.C.,
RA Dawson P.A.;
RT "Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects
RT with familial hypertriglyceridemia.";
RL Arterioscler. Thromb. Vasc. Biol. 21:2039-2045(2001).
RN [10]
RP VARIANTS ILE-98 AND ALA-171.
RX PubMed=11589382; DOI=10.1080/003655201750422693;
RA Montagnani M., Love M.W., Rossel P., Dawson P.A., Qvist P.;
RT "Absence of dysfunctional ileal sodium-bile acid cotransporter gene
RT mutations in patients with adult-onset idiopathic bile acid
RT malabsorption.";
RL Scand. J. Gastroenterol. 36:1077-1080(2001).
CC -!- FUNCTION: Plays a critical role in the sodium-dependent reabsorption of
CC bile acids from the lumen of the small intestine. Plays a key role in
CC cholesterol metabolism.
CC -!- SUBUNIT: Monomer and homodimer.
CC -!- INTERACTION:
CC Q12908; Q8NHW4: CCL4L2; NbExp=3; IntAct=EBI-18114847, EBI-10271156;
CC Q12908; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-18114847, EBI-12019274;
CC Q12908; P52803: EFNA5; NbExp=3; IntAct=EBI-18114847, EBI-1753674;
CC Q12908; Q01628: IFITM3; NbExp=3; IntAct=EBI-18114847, EBI-7932862;
CC Q12908; Q8IXM6: NRM; NbExp=3; IntAct=EBI-18114847, EBI-10262547;
CC Q12908; Q9NZ42: PSENEN; NbExp=3; IntAct=EBI-18114847, EBI-998468;
CC Q12908; Q9Y6I9: TEX264; NbExp=3; IntAct=EBI-18114847, EBI-10329860;
CC Q12908; Q9H0R3: TMEM222; NbExp=3; IntAct=EBI-18114847, EBI-347385;
CC Q12908; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-18114847, EBI-10243654;
CC Q12908; O75841: UPK1B; NbExp=3; IntAct=EBI-18114847, EBI-12237619;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- DISEASE: Primary bile acid malabsorption (PBAM) [MIM:613291]: An
CC intestinal disorder associated with chronic watery diarrhea, excess
CC fecal bile acids, steatorrhea and interruption of the enterohepatic
CC circulation of bile acids. {ECO:0000269|PubMed:9109432}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the bile acid:sodium symporter (BASS) (TC
CC 2.A.28) family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U10417; AAC51870.1; -; mRNA.
DR EMBL; U67674; AAC95398.1; -; Genomic_DNA.
DR EMBL; U67669; AAC95398.1; JOINED; Genomic_DNA.
DR EMBL; U67670; AAC95398.1; JOINED; Genomic_DNA.
DR EMBL; U67671; AAC95398.1; JOINED; Genomic_DNA.
DR EMBL; U67672; AAC95398.1; JOINED; Genomic_DNA.
DR EMBL; U67673; AAC95398.1; JOINED; Genomic_DNA.
DR EMBL; AE014294; AAN16026.1; -; Genomic_DNA.
DR EMBL; AL161771; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471085; EAX09074.1; -; Genomic_DNA.
DR EMBL; BC130521; AAI30522.1; -; mRNA.
DR EMBL; BC130523; AAI30524.1; -; mRNA.
DR EMBL; Z54350; CAA91161.1; -; Genomic_DNA.
DR CCDS; CCDS9506.1; -.
DR PIR; I38655; I38655.
DR RefSeq; NP_000443.1; NM_000452.2.
DR AlphaFoldDB; Q12908; -.
DR SMR; Q12908; -.
DR BioGRID; 112444; 12.
DR IntAct; Q12908; 11.
DR STRING; 9606.ENSP00000245312; -.
DR BindingDB; Q12908; -.
DR ChEMBL; CHEMBL2778; -.
DR DrugBank; DB00787; Acyclovir.
DR DrugBank; DB02659; Cholic Acid.
DR DrugBank; DB00091; Cyclosporine.
DR DrugBank; DB03619; Deoxycholic acid.
DR DrugBank; DB02123; Glycochenodeoxycholic Acid.
DR DrugBank; DB09237; Levamlodipine.
DR DrugBank; DB16226; Maralixibat.
DR DrugBank; DB16261; Odevixibat.
DR DrugBank; DB04348; Taurocholic acid.
DR DrugBank; DB01586; Ursodeoxycholic acid.
DR DrugBank; DB00577; Valaciclovir.
DR DrugBank; DB13914; Volixibat.
DR DrugCentral; Q12908; -.
DR GuidetoPHARMACOLOGY; 960; -.
DR TCDB; 2.A.28.1.2; the bile acid:na(+) symporter (bass) family.
DR GlyGen; Q12908; 1 site.
DR iPTMnet; Q12908; -.
DR PhosphoSitePlus; Q12908; -.
DR SwissPalm; Q12908; -.
DR BioMuta; SLC10A2; -.
DR DMDM; 322510055; -.
DR MassIVE; Q12908; -.
DR PaxDb; Q12908; -.
DR PeptideAtlas; Q12908; -.
DR PRIDE; Q12908; -.
DR Antibodypedia; 11241; 204 antibodies from 31 providers.
DR DNASU; 6555; -.
DR Ensembl; ENST00000245312.5; ENSP00000245312.3; ENSG00000125255.7.
DR GeneID; 6555; -.
DR KEGG; hsa:6555; -.
DR MANE-Select; ENST00000245312.5; ENSP00000245312.3; NM_000452.3; NP_000443.2.
DR UCSC; uc001vpy.4; human.
DR CTD; 6555; -.
DR DisGeNET; 6555; -.
DR GeneCards; SLC10A2; -.
DR HGNC; HGNC:10906; SLC10A2.
DR HPA; ENSG00000125255; Tissue enriched (intestine).
DR MalaCards; SLC10A2; -.
DR MIM; 601295; gene.
DR MIM; 613291; phenotype.
DR neXtProt; NX_Q12908; -.
DR OpenTargets; ENSG00000125255; -.
DR Orphanet; 449262; NON RARE IN EUROPE: Primary bile acid malabsorption.
DR PharmGKB; PA318; -.
DR VEuPathDB; HostDB:ENSG00000125255; -.
DR eggNOG; KOG2718; Eukaryota.
DR GeneTree; ENSGT00950000182808; -.
DR HOGENOM; CLU_034788_7_5_1; -.
DR InParanoid; Q12908; -.
DR OMA; LYQSSWI; -.
DR OrthoDB; 1148347at2759; -.
DR PhylomeDB; Q12908; -.
DR TreeFam; TF315811; -.
DR PathwayCommons; Q12908; -.
DR Reactome; R-HSA-159418; Recycling of bile acids and salts.
DR SignaLink; Q12908; -.
DR BioGRID-ORCS; 6555; 6 hits in 1060 CRISPR screens.
DR GeneWiki; SLC10A2; -.
DR GenomeRNAi; 6555; -.
DR Pharos; Q12908; Tclin.
DR PRO; PR:Q12908; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q12908; protein.
DR Bgee; ENSG00000125255; Expressed in ileal mucosa and 33 other tissues.
DR Genevisible; Q12908; HS.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008508; F:bile acid:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0015721; P:bile acid and bile salt transport; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR Gene3D; 1.20.1530.20; -; 1.
DR InterPro; IPR002657; BilAc:Na_symport/Acr3.
DR InterPro; IPR004710; Bilac:Na_transpt.
DR InterPro; IPR038770; Na+/solute_symporter_sf.
DR InterPro; IPR030207; SLC10A2.
DR PANTHER; PTHR10361; PTHR10361; 1.
DR PANTHER; PTHR10361:SF19; PTHR10361:SF19; 1.
DR Pfam; PF01758; SBF; 1.
DR TIGRFAMs; TIGR00841; bass; 1.
PE 1: Evidence at protein level;
KW Disease variant; Glycoprotein; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Sodium; Sodium transport; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..348
FT /note="Ileal sodium/bile acid cotransporter"
FT /id="PRO_0000052339"
FT TOPO_DOM 1..28
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 29..49
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 50..82
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 83..103
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 104..126
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 148..157
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 179..195
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..216
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 217..224
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 246..284
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 285..305
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 306..348
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 320..348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 328
FT /note="Not glycosylated"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70172"
FT CARBOHYD 10
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15350125"
FT VARIANT 98
FT /note="V -> I (in dbSNP:rs55971546)"
FT /evidence="ECO:0000269|PubMed:11589382,
FT ECO:0000269|PubMed:11742882"
FT /id="VAR_024837"
FT VARIANT 159
FT /note="V -> I (in dbSNP:rs60380298)"
FT /evidence="ECO:0000269|PubMed:11742882"
FT /id="VAR_024838"
FT VARIANT 171
FT /note="S -> A (in dbSNP:rs188096)"
FT /evidence="ECO:0000269|PubMed:11589382,
FT ECO:0000269|PubMed:11742882, ECO:0000269|PubMed:12364586,
FT ECO:0000269|PubMed:15057823, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7592981, ECO:0000269|PubMed:9109432"
FT /id="VAR_004613"
FT VARIANT 243
FT /note="L -> P (in PBAM; abolishes taurocholate transport;
FT dbSNP:rs121917848)"
FT /evidence="ECO:0000269|PubMed:9109432"
FT /id="VAR_004614"
FT VARIANT 262
FT /note="T -> M (in PBAM; abolishes taurocholate transport;
FT dbSNP:rs72547505)"
FT /evidence="ECO:0000269|PubMed:9109432"
FT /id="VAR_004615"
FT VARIANT 290
FT /note="P -> S (in a patient with Crohn disease; abolishes
FT taurocholate transport; dbSNP:rs56398830)"
FT /evidence="ECO:0000269|PubMed:7592981"
FT /id="VAR_004616"
FT MUTAGEN 10
FT /note="N->D: Abolishes glycosylation."
FT /evidence="ECO:0000269|PubMed:15350125"
FT MUTAGEN 328
FT /note="N->D: No effect on glycosylation."
FT /evidence="ECO:0000269|PubMed:15350125"
SQ SEQUENCE 348 AA; 37714 MW; 9794EAA77C3EC4F9 CRC64;
MNDPNSCVDN ATVCSGASCV VPESNFNNIL SVVLSTVLTI LLALVMFSMG CNVEIKKFLG
HIKRPWGICV GFLCQFGIMP LTGFILSVAF DILPLQAVVV LIIGCCPGGT ASNILAYWVD
GDMDLSVSMT TCSTLLALGM MPLCLLIYTK MWVDSGSIVI PYDNIGTSLV SLVVPVSIGM
FVNHKWPQKA KIILKIGSIA GAILIVLIAV VGGILYQSAW IIAPKLWIIG TIFPVAGYSL
GFLLARIAGL PWYRCRTVAF ETGMQNTQLC STIVQLSFTP EELNVVFTFP LIYSIFQLAF
AAIFLGFYVA YKKCHGKNKA EIPESKENGT EPESSFYKAN GGFQPDEK
