Q14973 · NTCP_HUMAN
- ProteinHepatic sodium/bile acid cotransporter
- GeneSLC10A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids349 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
As a major transporter of conjugated bile salts from plasma into the hepatocyte, it plays a key role in the enterohepatic circulation of bile salts necessary for the solubilization and absorption of dietary fat and fat-soluble vitamins (PubMed:14660639, PubMed:24867799, PubMed:34060352, PubMed:8132774).
It is strictly dependent on the extracellular presence of sodium (PubMed:14660639, PubMed:24867799, PubMed:34060352, PubMed:8132774).
It exhibits broad substrate specificity and transports various bile acids, such as taurocholate, cholate, as well as non-bile acid organic compounds, such as estrone sulfate (PubMed:14660639, PubMed:34060352).
Works collaboratively with the ileal transporter (NTCP2), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (PubMed:33222321).
It is strictly dependent on the extracellular presence of sodium (PubMed:14660639, PubMed:24867799, PubMed:34060352, PubMed:8132774).
It exhibits broad substrate specificity and transports various bile acids, such as taurocholate, cholate, as well as non-bile acid organic compounds, such as estrone sulfate (PubMed:14660639, PubMed:34060352).
Works collaboratively with the ileal transporter (NTCP2), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (PubMed:33222321).
(Microbial infection) Acts as a receptor for hepatitis B virus.
Catalytic activity
- 2 Na+(out) + taurocholate(out) = 2 Na+(in) + taurocholate(in)
2 Na+ (out)CHEBI:29101+ taurocholate (out)CHEBI:36257= 2 Na+ (in)CHEBI:29101+ taurocholate (in)CHEBI:36257 - cholate(out) + 2 Na+(out) = cholate(in) + 2 Na+(in)
- estrone 3-sulfate(out) + 2 Na+(out) = estrone 3-sulfate(in) + 2 Na+(in)
- 2 Na+(out) + taurochenodeoxycholate(out) = 2 Na+(in) + taurochenodeoxycholate(in)
- 2 Na+(out) + tauroursodeoxycholate(out) = 2 Na+(in) + tauroursodeoxycholate(in)
- glycocholate(out) + 2 Na+(out) = glycocholate(in) + 2 Na+(in)
- 2 Na+(out) + tauronorcholate(out) = 2 Na+(in) + tauronorcholate(in)
- 2 Na+(out) + taurodeoxycholate(out) = 2 Na+(in) + taurodeoxycholate(in)
- 2 Na+(out) + tauroallocholate(out) = 2 Na+(in) + tauroallocholate(in)
- 2 Na+(out) + taurohyodeoxycholate(out) = 2 Na+(in) + taurohyodeoxycholate(in)
- 2 Na+(out) + taurohyocholate(out) = 2 Na+(in) + taurohyocholate(in)
- 2 Na+(out) + tauro-beta-muricholate(out) = 2 Na+(in) + tauro-beta-muricholate(in)
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
6.3 μM | taurocholate | |||||
10 μM | taurocholate | |||||
7.5 μM | taurocholate | |||||
15 μM | taurocholate | |||||
12 μM | cholate | |||||
60 μM | estrone 3-sulfate | |||||
27 μM | estrone 3-sulfate | |||||
67 μM | estrone 3-sulfate |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
333 pmol/min/mg | with taurocholate as substrate | ||||
415 pmol/min/mg | with taurocholate as substrate | ||||
139 pmol/min/mg | with cholate as substrate | ||||
111 pmol/min/mg | with estrone 3-sulfate as substrate | ||||
68 pmol/min/mg | with estrone 3-sulfate as substrate | ||||
1060 pmol/min/mg | with estrone 3-sulfate as substrate | ||||
130 pmol/min/mg | with taurocholate as substrate |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | basolateral plasma membrane | |
Cellular Component | plasma membrane | |
Molecular Function | bile acid:sodium symporter activity | |
Molecular Function | virus receptor activity | |
Biological Process | bile acid and bile salt transport | |
Biological Process | bile acid signaling pathway | |
Biological Process | cellular response to xenobiotic stimulus | |
Biological Process | regulation of bile acid secretion | |
Biological Process | response to estrogen | |
Biological Process | response to ethanol | |
Biological Process | response to nutrient levels | |
Biological Process | response to organic cyclic compound |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameHepatic sodium/bile acid cotransporter
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ14973
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 25-45 | Helical | ||||
Sequence: LALSVILVFMLFFIMLSLGCT | ||||||
Transmembrane | 60-80 | Helical | ||||
Sequence: GLAIALVAQYGIMPLTAFVLG | ||||||
Transmembrane | 91-111 | Helical | ||||
Sequence: LAILVCGCSPGGNLSNVFSLA | ||||||
Transmembrane | 120-140 | Helical | ||||
Sequence: IVMTTCSTFCALGMMPLLLYI | ||||||
Transmembrane | 156-176 | Helical | ||||
Sequence: YKGIVISLVLVLIPCTIGIVL | ||||||
Transmembrane | 191-211 | Helical | ||||
Sequence: GMIIILLCSVAVTVLSAINVG | ||||||
Transmembrane | 220-240 | Helical | ||||
Sequence: PLLIATSSLMPFIGFLLGYVL | ||||||
Transmembrane | 283-303 | Helical | ||||
Sequence: FFFPLLYMIFQLGEGLLLIAI |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Hypercholanemia, familial, 2 (FHCA2)
- Note
- DescriptionAn autosomal recessive inborn error of metabolism characterized by persistently increased plasma levels of conjugated bile salts apparent from infancy, fat malabsorption and impaired absorption of fat-soluble vitamins, including D and K. Most patients are asymptomatic. Some neonates may have transient jaundice or transiently elevated liver enzymes.
- See alsoMIM:619256
Natural variants in FHCA2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_085565 | 88 | I>T | in FHCA2; decreased function in taurocholate transport; dbSNP:rs148467625 | |
VAR_085570 | 199 | S>R | in FHCA2; dbSNP:rs746174545 | |
VAR_085577 | 252 | R>H | in FHCA2; loss of function in taurocholate transport; loss of localization to the cell membrane due to intracellular retention; dbSNP:rs147226818 | |
VAR_022113 | 267 | S>F | in FHCA2; protective factor against hepatitis B virus infection and chronic hepatitis; unable to transport taurocholate and cholate; does not affect uptake of estrone sulfate; does not affect localization to the cell membrane; dbSNP:rs2296651 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_085560 | 21 | decreased function in taurocholate transport; dbSNP:rs200758433 | |||
Sequence: R → C | ||||||
Natural variant | VAR_085561 | 39 | decreased function in taurocholate transport; dbSNP:rs536458730 | |||
Sequence: M → T | ||||||
Natural variant | VAR_085562 | 41 | decreased function in taurocholate transport; dbSNP:rs111885789 | |||
Sequence: S → L | ||||||
Natural variant | VAR_085563 | 64 | decreased function in taurocholate transport; dbSNP:rs202018997 | |||
Sequence: A → T | ||||||
Natural variant | VAR_085564 | 73 | severely decreased function in taurocholate transport; dbSNP:rs763683476 | |||
Sequence: P → T | ||||||
Natural variant | VAR_085565 | 88 | in FHCA2; decreased function in taurocholate transport; dbSNP:rs148467625 | |||
Sequence: I → T | ||||||
Natural variant | VAR_085566 | 138 | loss of function in taurocholate transport; dbSNP:rs543063679 | |||
Sequence: L → P | ||||||
Natural variant | VAR_085567 | 159 | decreased function in taurocholate transport; dbSNP:rs144006534 | |||
Sequence: I → M | ||||||
Natural variant | VAR_085568 | 180 | decreased function in taurocholate transport; dbSNP:rs571796903 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_085569 | 190 | decreased function in taurocholate transport; dbSNP:rs553948182 | |||
Sequence: G → E | ||||||
Natural variant | VAR_085570 | 199 | in FHCA2; dbSNP:rs746174545 | |||
Sequence: S → R | ||||||
Natural variant | VAR_085571 | 223 | decreased transport of taurocholate and cholate; decreased transport of estron sulfate; decreased expression at the cell membrane due to intracellular retention; dbSNP:rs61745930 | |||
Sequence: I → T | ||||||
Natural variant | VAR_085572 | 232 | slightly decreased function in taurocholate transport; dbSNP:rs190268737 | |||
Sequence: I → T | ||||||
Natural variant | VAR_085573 | 234 | severely decreased function in taurocholate transport; dbSNP:rs139931299 | |||
Sequence: F → L | ||||||
Natural variant | VAR_085574 | 241 | loss of function in taurocholate transport; dbSNP:rs150579813 | |||
Sequence: S → F | ||||||
Natural variant | VAR_085575 | 249 | severely decreased function in taurocholate transport; dbSNP:rs76966244 | |||
Sequence: R → W | ||||||
Natural variant | VAR_085576 | 252 | severely decreased function in taurocholate transport; dbSNP:rs141269120 | |||
Sequence: R → C | ||||||
Natural variant | VAR_085577 | 252 | in FHCA2; loss of function in taurocholate transport; loss of localization to the cell membrane due to intracellular retention; dbSNP:rs147226818 | |||
Sequence: R → H | ||||||
Natural variant | VAR_085578 | 252 | severely decreased function in taurocholate transport; dbSNP:rs141269120 | |||
Sequence: R → S | ||||||
Natural variant | VAR_085579 | 258 | decreased function in taurocholate transport; dbSNP:rs541801766 | |||
Sequence: T → S | ||||||
Natural variant | VAR_022113 | 267 | in FHCA2; protective factor against hepatitis B virus infection and chronic hepatitis; unable to transport taurocholate and cholate; does not affect uptake of estrone sulfate; does not affect localization to the cell membrane; dbSNP:rs2296651 | |||
Sequence: S → F | ||||||
Natural variant | VAR_085580 | 279 | decreased transport of taurocholate and cholate; decreased transport of estron sulfate; does not affect localization to the cell membrane; dbSNP:rs72547507 | |||
Sequence: I → T | ||||||
Natural variant | VAR_085581 | 293 | decreased function in taurocholate transport; dbSNP:rs189313778 | |||
Sequence: Q → E | ||||||
Natural variant | VAR_085582 | 314 | decreased transport of taurocholate and cholate; decreased transport of estron sulfate; does not affect localization to the cell membrane; dbSNP:rs72547506 | |||
Sequence: K → E |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 520 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000052335 | 1-349 | Hepatic sodium/bile acid cotransporter | |||
Sequence: MEAHNASAPFNFTLPPNFGKRPTDLALSVILVFMLFFIMLSLGCTMEFSKIKAHLWKPKGLAIALVAQYGIMPLTAFVLGKVFRLKNIEALAILVCGCSPGGNLSNVFSLAMKGDMNLSIVMTTCSTFCALGMMPLLLYIYSRGIYDGDLKDKVPYKGIVISLVLVLIPCTIGIVLKSKRPQYMRYVIKGGMIIILLCSVAVTVLSAINVGKSIMFAMTPLLIATSSLMPFIGFLLGYVLSALFCLNGRCRRTVSMETGCQNVQLCSTILNVAFPPEVIGPLFFFPLLYMIFQLGEGLLLIAIFWCYEKFKTPKDKTKMIYTAATTEETIPGALGNGTYKGEDCSPCTA | ||||||
Glycosylation | 5 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 11 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 117 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 336 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
(Microbial infection) Interacts with hepatitis B virus large envelope protein.
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length349
- Mass (Da)38,119
- Last updated1996-11-01 v1
- ChecksumF3AB2CC2FBD925E3
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L21893 EMBL· GenBank· DDBJ | AAA36381.1 EMBL· GenBank· DDBJ | mRNA | ||
AY544127 EMBL· GenBank· DDBJ | AAT11158.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471061 EMBL· GenBank· DDBJ | EAW81011.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC069799 EMBL· GenBank· DDBJ | AAH69799.1 EMBL· GenBank· DDBJ | mRNA | ||
BC069822 EMBL· GenBank· DDBJ | AAH69822.1 EMBL· GenBank· DDBJ | mRNA | ||
BC074724 EMBL· GenBank· DDBJ | AAH74724.1 EMBL· GenBank· DDBJ | mRNA | ||
BC126298 EMBL· GenBank· DDBJ | AAI26299.1 EMBL· GenBank· DDBJ | mRNA | ||
BC136355 EMBL· GenBank· DDBJ | AAI36356.1 EMBL· GenBank· DDBJ | mRNA |