Slc10a1 (mouse Ntcp) curation notes

Provenance of this review

Automated deep research was not available in this container, so the literature
synthesis below was assembled by hand from the cached publications in publications/
plus the UniProt record (O08705) and the GOA file:

Falcon/Edison provider returned 402 Payment Required; OpenAI provider returned
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No -deep-research-*.md file was written (per CLAUDE.md, hand-written content must
never be named as a deep-research provider output).

This review was done immediately after genes/human/SLC10A1, and the human notes file
carries the synthesized picture for the orthologue; this file records what is
specifically established for the mouse protein and where mouse and human diverge.

Gene identity

UniProt: O08705 (NTCP_MOUSE; Hepatic sodium/bile acid cotransporter; Slc10a1 / Ntcp)
362 aa, multi-pass membrane protein; bile acid:sodium symporter (BASS, TC 2.A.28)
family; InterPro IPR002657
Two alternatively spliced isoforms, both functional transporters
PMID:10209268

Core transport function (direct mouse evidence)

Both mouse isoforms are Na+-dependent taurocholate transporters
PMID:10209268
UniProt records the curated stoichiometry as 2 Na+ per bile salt (RHEA:71875 for
taurocholate, RHEA:71083 for estrone 3-sulfate) with mouse-specific kinetics:
KM = 86 uM taurocholate (isoform 1), 14 uM (isoform 2), 104 uM estrone-3-sulfate.
Mouse Ntcp is functionally close to human NTCP for both a probe substrate and a drug
PMID:34060352
Localization and physiological direction of transport
PMID:34060352
In vivo, mouse hepatic Slc10a1 is the basolateral uptake step whose loss of expression
impairs portal bile acid uptake
PMID:11279518

Species divergence: mouse Ntcp is NOT a functional HBV/HDV receptor

This is the point that matters most for judging transfers in this family, because human
NTCP's best-known non-transport property does not transfer to mouse.

Human NTCP is necessary and sufficient to confer susceptibility in culture
PMID:23150796
Mouse Ntcp is not
PMID:23678176
PMID:23678176
The restriction maps to the first extracellular loop and is reversible by humanizing
four residues
PMID:23678176
Importantly, the restriction is not a loss of transport: mouse Ntcp retains full
symport activity in the same assay
PMID:23678176
Consequence for curation: the two NEW annotations proposed on human SLC10A1
(GO:0001618 virus receptor activity, GO:0046718 symbiont entry into host cell) must
not be propagated to mouse Slc10a1. Residual pre-S1 lipopeptide binding is
documented, but binding without supporting entry is not receptor activity, and GO:0046718
is contradicted outright. Any future ISO/IBA transfer of those terms onto O08705 should be
treated as a FUNCTIONAL_DIVERGENCE propagation failure.

Donor tracing for the propagated rows

All 14 GOA rows are propagated except one IDA. Donors traced from the WITH/FROM column of
Slc10a1-goa.tsv, with the donor annotations' own evidence checked in the rat and human
GOA files in this repository:

Donor	Identity	Donor evidence for the transferred term
RGD:3681	rat Slc10a1 (P26435)	IDA: GO:0008508 + GO:0015721 (PMID:1961729), GO:0015125 + GO:0016323 (PMID:15297262), GO:0016323 (PMID:17082223)
RGD:3682	rat Slc10a2 (Asbt)	paralog, apical ileal transporter; legitimate co-descendant seed for the symport node, not for basolateral localization
MGI:MGI:1201406	mouse Slc10a2	paralog; seeds the generic plasma-membrane node only
UniProtKB:Q14973	human SLC10A1	IDA: GO:0005886 + GO:0015125 (PMID:22029531)
UniProtKB:Q96EP9	human SLC10A4	paralog; generic plasma-membrane node only
UniProtKB:P26435	rat Ntcp	ISS donor for GO:0016323; rat has IDA for that term
PANTHER:PTN000040759	plasma-membrane node, whole SLC10 family	—
PANTHER:PTN000040761	symport/bile-acid-transport node, NTCP+ASBT clade	—
PANTHER:PTN002570905	NTCP-specific node, basolateral (correctly excludes the apical ASBT branch)	—

No donor was judged problematic. In particular, none of the ISO rows was marked
CIRCULAR_OR_REDUNDANT: mouse Ntcp having its own direct functional evidence
(PMID:10209268, PMID:34060352) does not make a well-grounded experimental transfer
circular — the donor annotations are IDA, not propagations, and the chains contain no
transfer-of-a-transfer. Per CLAUDE.md, that status is reserved for genuine circularity.

Curation decisions and their reasoning

Transport MF/BP and plasma-membrane CC rows → ACCEPT (GO:0008508, GO:0015125,
GO:0015721, GO:0005886, GO:0016323, and the broad GO:0016020 IEA). The node placements
are sound and the transfers land on a protein whose own experimental data match the
donors' (Na+-dependent taurocholate symport, basolateral hepatocyte membrane).
GO:0015125 is the less specific parent of GO:0008508; duplication at two granularities
is acceptable and both are retained.
GO:0016020 membrane IDA (PMID:11279518) → MODIFY → GO:0016323 basolateral plasma membrane. The essence is right but the term is uninformative at the level of a
single IDA, and the cited paper itself places Slc10a1 in the basolateral membrane
(quote above). The sibling IEA GO:0016020 row is left as ACCEPT, since a broad
electronic parent of correctly annotated children is harmless.
No NEW annotations proposed. Every activity, process and location that mouse Ntcp
is known to perform is already represented. The virus-receptor pair is excluded on the
species-divergence evidence above. Transport of non-bile-acid substrates
(estrone-3-sulfate, rosuvastatin) is real but was demonstrated in transfected-cell
uptake assays; whether that warrants a xenobiotic-transport process term is raised in
suggested_questions rather than asserted.

Open items

GOA carries no direct experimental molecular-function annotation for mouse Ntcp,
even though PMID:10209268 is a straightforward IDA-grade Xenopus oocyte uptake
experiment on both mouse isoforms, and PMID:34060352 adds kinetics. The transport terms
rest entirely on ISO/IBA. A direct IDA from PMID:10209268 would be a strict improvement
and is raised as a suggested question.
Isoform 2 (O08705-2, VSP_061644) has a roughly sixfold higher taurocholate affinity than
isoform 1 (KM 14 vs 86 uM, PMID:10209268) but no isoform-resolved GO annotation exists.
No GO-CAM model containing mouse Slc10a1 was found in gocams/index.tsv at review time.

2026-10-12 Ortholog/family audit

GOA refetched (no new rows); review already COMPLETE and unchanged. PANTHER PTHR10361:SF40 (hepatic Na/bile acid cotransporter) confirmed from UniProt; IBA nodes PTN000040759/40761/002570905 appropriate. Core function (GO:0008508 symporter -> GO:0015721 transport, at GO:0016323 basolateral membrane) is consistent with rat Slc10a1 and human SLC10A1.

Key species-divergence point verified and correctly handled: unlike human NTCP, mouse Ntcp is NOT a functional HBV/HDV entry receptor — it binds preS1 and transports taurocholate normally but cannot support infection, mapped to residues 84-87 PMID:23678176. The mouse review therefore omits the virus-receptor terms (GO:0001618/GO:0046718) that human SLC10A1 carries as NEW, and raises a suggested_question about a NOT annotation/taxon constraint to block their automated transfer. Rat Slc10a1 likewise carries no receptor terms. Consistent across all three. The GO:0016020 ACCEPT(IEA)/MODIFY(IDA) validator warning is a deliberate, documented choice (IDA names observed membrane; family-signature IEA cannot resolve polarity).