Q12908 (NTCP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ileal sodium/bile acid cotransporter

Alternative name(s):
Apical sodium-dependent bile acid transporter
Short name=ASBT
Ileal Na(+)/bile acid cotransporter
Ileal sodium-dependent bile acid transporter
Short name=IBAT
Short name=ISBT
Na(+)-dependent ileal bile acid transporter
Sodium/taurocholate cotransporting polypeptide, ileal
Solute carrier family 10 member 2

Gene names

Name:	SLC10A2
Synonyms:	ASBT, ISBT, NTCP2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	348 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism.
Subunit structure	Monomer and homodimer.
Subcellular location	Membrane; Multi-pass membrane protein.
Involvement in disease	Primary bile acid malabsorption (PBAM) [MIM:613291]: An intestinal disorder associated with chronic watery diarrhea, excess fecal bile acids, steatorrhea and interruption of the enterohepatic circulation of bile acids. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2
Sequence similarities	Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family. [View classification]

Ontologies

Keywords
Biological process	Ion transport Sodium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bile acid metabolic process Traceable author statement. Source: Reactome
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc nucleus Inferred from electronic annotation. Source: Compara proteasome complex Inferred from electronic annotation. Source: Compara
Molecular_function	bile acid:sodium symporter activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 348	348	Ileal sodium/bile acid cotransporter		PRO_0000052339
Regions
	Topological domain	1 – 28	28	Extracellular Potential
	Transmembrane	29 – 49	21	Helical; Potential
	Topological domain	50 – 82	33	Cytoplasmic Potential
	Transmembrane	83 – 103	21	Helical; Potential
	Topological domain	104 – 126	23	Extracellular Potential
	Transmembrane	127 – 147	21	Helical; Potential
	Topological domain	148 – 157	10	Cytoplasmic Potential
	Transmembrane	158 – 178	21	Helical; Potential
	Topological domain	179 – 195	17	Extracellular Potential
	Transmembrane	196 – 216	21	Helical; Potential
	Topological domain	217 – 224	8	Cytoplasmic Potential
	Transmembrane	225 – 245	21	Helical; Potential
	Topological domain	246 – 284	39	Extracellular Potential
	Transmembrane	285 – 305	21	Helical; Potential
	Topological domain	306 – 348	43	Cytoplasmic Potential
Sites
	Site	328	1	Not glycosylated
Amino acid modifications
	Glycosylation	10	1	N-linked (GlcNAc...) Ref.8
Natural variations
	Natural variant	98	1	V → I. Ref.9 Ref.10 Corresponds to variant rs55971546 [ dbSNP | Ensembl ].		VAR_024837
	Natural variant	159	1	V → I. Ref.9 Corresponds to variant rs60380298 [ dbSNP | Ensembl ].		VAR_024838
	Natural variant	171	1	S → A. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.9 Ref.10 Corresponds to variant rs188096 [ dbSNP | Ensembl ].		VAR_004613
	Natural variant	243	1	L → P in PBAM; abolishes taurocholate transport. Ref.2		VAR_004614
	Natural variant	262	1	T → M in PBAM; abolishes taurocholate transport. Ref.2		VAR_004615
	Natural variant	290	1	P → S in a patient with Crohn disease; abolishes taurocholate transport. Ref.1 Corresponds to variant rs56398830 [ dbSNP | Ensembl ].		VAR_004616
Experimental info
	Mutagenesis	10	1	N → D: Abolishes glycosylation. Ref.8
	Mutagenesis	328	1	N → D: No effect on glycosylation. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Q12908 [UniParc]. Last modified February 8, 2011. Version 2. Checksum: 9794EAA77C3EC4F9	FASTA	348	37,714
	10 20 30 40 50 60 MNDPNSCVDN ATVCSGASCV VPESNFNNIL SVVLSTVLTI LLALVMFSMG CNVEIKKFLG 70 80 90 100 110 120 HIKRPWGICV GFLCQFGIMP LTGFILSVAF DILPLQAVVV LIIGCCPGGT ASNILAYWVD 130 140 150 160 170 180 GDMDLSVSMT TCSTLLALGM MPLCLLIYTK MWVDSGSIVI PYDNIGTSLV SLVVPVSIGM 190 200 210 220 230 240 FVNHKWPQKA KIILKIGSIA GAILIVLIAV VGGILYQSAW IIAPKLWIIG TIFPVAGYSL 250 260 270 280 290 300 GFLLARIAGL PWYRCRTVAF ETGMQNTQLC STIVQLSFTP EELNVVFTFP LIYSIFQLAF 310 320 330 340 AAIFLGFYVA YKKCHGKNKA EIPESKENGT EPESSFYKAN GGFQPDEK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity." Wong M.H., Oelkers P., Dawson P.A. J. Biol. Chem. 270:27228-27234(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ALA-171 AND CD SER-290. Tissue: Ileum.
[2]	"Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2)." Oelkers P., Kirby L.C., Heubi J.E., Dawson P.A. J. Clin. Invest. 99:1880-1887(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PBAM PRO-243 AND MET-262, VARIANT ALA-171.
[3]	"Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia." Chumakov I., Blumenfeld M., Guerassimenko O., Cavarec L., Palicio M., Abderrahim H., Bougueleret L., Barry C., Tanaka H., La Rosa P., Puech A., Tahri N., Cohen-Akenine A., Delabrosse S., Lissarrague S., Picard F.-P., Maurice K., Essioux L. , Millasseau P., Grel P., Debailleul V., Simon A.-M., Caterina D., Dufaure I., Malekzadeh K., Belova M., Luan J.-J., Bouillot M., Sambucy J.-L., Primas G., Saumier M., Boubkiri N., Martin-Saumier S., Nasroune M., Peixoto H., Delaye A., Pinchot V., Bastucci M., Guillou S., Chevillon M., Sainz-Fuertes R., Meguenni S., Aurich-Costa J., Cherif D., Gimalac A., Van Duijn C., Gauvreau D., Ouellette G., Fortier I., Raelson J., Sherbatich T., Riazanskay N., Rogaev E., Raeymaekers P., Aerssens J., Konings F., Luyten W., Macciardi F., Sham P.C., Straub R.E., Weinberger D.R., Cohen N., Cohen D. Proc. Natl. Acad. Sci. U.S.A. 99:13675-13680(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-171.
[4]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-171.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-171.
[7]	"Human ileal sodium-dependent bile acid transporter gene (promoter, exon 1 and intron 1)." Stengelin S., Becker W., Maier M., Rosenberger J., Kramer W. Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22. Tissue: Blood.
[8]	"Topology scanning and putative three-dimensional structure of the extracellular binding domains of the apical sodium-dependent bile acid transporter (SLC10A2)." Zhang E.Y., Phelps M.A., Banerjee A., Khantwal C.M., Chang C., Helsper F., Swaan P.W. Biochemistry 43:11380-11392(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-10, MUTAGENESIS OF ASN-10 AND ASN-328, TOPOLOGY.
[9]	"Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia." Love M.W., Craddock A.L., Angelin B., Brunzell J.D., Duane W.C., Dawson P.A. Arterioscler. Thromb. Vasc. Biol. 21:2039-2045(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-98; ILE-159 AND ALA-171.
[10]	"Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption." Montagnani M., Love M.W., Rossel P., Dawson P.A., Qvist P. Scand. J. Gastroenterol. 36:1077-1080(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-98 AND ALA-171.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U10417 mRNA. Translation: AAC51870.1. U67674 , U67669, U67670, U67671, U67672, U67673 Genomic DNA. Translation: AAC95398.1. AE014294 Genomic DNA. Translation: AAN16026.1. AL161771 Genomic DNA. Translation: CAC39447.1. CH471085 Genomic DNA. Translation: EAX09074.1. BC130521 mRNA. Translation: AAI30522.1. BC130523 mRNA. Translation: AAI30524.1. Z54350 Genomic DNA. Translation: CAA91161.1.
IPI	IPI00030208.
PIR	I38655.
RefSeq	NP_000443.1. NM_000452.2.
UniGene	Hs.194783.
3D structure databases
ProteinModelPortal	Q12908.
SMR	Q12908. Positions 32-311.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000245312.
Protein family/group databases
TCDB	2.A.28.1.2. bile acid:Na+ symporter (BASS) family.
PTM databases
PhosphoSite	Q12908.
Polymorphism databases
DMDM	2833238.
Proteomic databases
PaxDb	Q12908.
PRIDE	Q12908.
Protocols and materials databases
DNASU	6555.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000245312; ENSP00000245312; ENSG00000125255.
GeneID	6555.
KEGG	hsa:6555.
UCSC	uc001vpy.4. human.
Organism-specific databases
CTD	6555.
GeneCards	GC13M103696.
HGNC	HGNC:10906. SLC10A2.
HPA	HPA004795.
MIM	601295. gene. 613291. phenotype.
neXtProt	NX_Q12908.
PharmGKB	PA318.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0385.
HOGENOM	HOG000234524.
HOVERGEN	HBG006537.
InParanoid	Q12908.
KO	K14342.
OMA	NSCVDNA.
OrthoDB	EOG4VQ9PM.
PhylomeDB	Q12908.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
Bgee	Q12908.
CleanEx	HS_SLC10A2.
Genevestigator	Q12908.
GermOnline	ENSG00000125255. Homo sapiens.
Family and domain databases
InterPro	IPR004710. Bil_ac_transpt. IPR002657. BilAc/Na_symport. [Graphical view]
PANTHER	PTHR10361. PTHR10361. 1 hit.
Pfam	PF01758. SBF. 1 hit. [Graphical view]
TIGRFAMs	TIGR00841. bass. 1 hit.
ProtoNet	Search...
Other
BindingDB	Q12908.
ChEMBL	CHEMBL2778.
GenomeRNAi	6555.
NextBio	25507.
SOURCE	Search...

Entry information

Entry name

NTCP2_HUMAN

Accession

Primary (citable) accession number: Q12908
Secondary accession number(s): A1L4F4, Q13839

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 8, 2011
Last modified:	May 1, 2013
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.