SLC10A1 (NTCP) curation notes

Provenance of this review

Automated deep research was attempted and failed for both configured providers, so
the literature synthesis below was assembled by hand from the cached publications in
publications/ plus the UniProt record:

No -deep-research-*.md file was written (per CLAUDE.md, hand-written content must
never be named as a deep-research provider output).

Gene identity

Core transport function

Substrate breadth (bile salts and beyond)

Oligomeric state

Human loss of function

HBV/HDV receptor function

Curation decisions and their reasoning

  1. 87 + 1 GO:0005515 protein binding rows → REMOVE. All come from two systematic
    interaction surveys (HuRI, PMID:32296183; SLC interactome, PMID:40355756) that assign
    no function. Per repo policy, generic protein binding is removed as uninformative
    rather than marked over-annotated, and removal does not dispute the interactions.
  2. Transport and localization rows → ACCEPT (GO:0008508, GO:0015125, GO:0015721,
    GO:0005886, GO:0016323, GO:0016020). The IBA node placements are sound: the
    NTCP/ASBT clade shares Na+-dependent bile acid symport, and the NTCP-specific
    sub-node (PANTHER:PTN002570905) is correctly basolateral, unlike the apical ileal
    ASBT branch. GO:0016020 is a broad IEA parent of correctly annotated children and is
    kept.
  3. GO:0031667 response to nutrient levels, GO:0043627 response to estrogen,
    GO:0045471 response to ethanol → REMOVE.     All three are GO_REF:0000107 transfers
    from rat Ntcp (UniProtKB:P26435) where the underlying observation is modulation of
    transporter expression/activity. Being regulated by a stimulus is not participating in
    the response to it; NTCP performs no step of nutrient sensing, estrogen signalling or
    ethanol metabolism. NTCP deficiency leaves bile salt synthesis and intestinal FGF19
    signalling intact (PMID:24867799), i.e. no evidence that NTCP acts within such
    responses. Note that estrone-3-sulfate transport is a substrate relationship, whose
    proper representation is a transporter activity term, not "response to estrogen".
  4. GO:0071466 cellular response to xenobiotic stimulus → MODIFY → GO:0042908 xenobiotic transport. Here there is a real activity, not just a regulatory
    effect: the liver carrier is explicitly described as multispecific and as
    participating in hepatic clearance of xenobiotics (PMID:9458785), and human NTCP
    transports rosuvastatin (PMID:34060352). But what the protein does is transport the
    xenobiotic, not respond to it. (GO:0015711 organic anion transport and GO:0008514
    organic anion transmembrane transporter activity are both obsolete — checked via OLS
    — so the xenobiotic transport term is the available fit.)
  5. Two NEW annotations: GO:0001618 virus receptor activity and GO:0046718 symbiont entry into host cell. Absent from GOA for Q14973 (checked via QuickGO),
    despite being one of the best-characterized facts about the human protein.
  6. Participation test: NTCP itself does the receptor work — direct preS1
    cross-linking, and necessity and sufficiency in cell culture (PMID:23150796) —
    and the transporter's conformational state governs preS1 exposure (PMID:35545671).
  7. Comparator check: ACE2 (Q9BYF1) and CD4 (P01730), both host proteins with their own
    enzymatic/immune function serving as entry receptors, carry GO:0001618 and
    GO:0046718 by IDA (QuickGO query). So the terms are conventionally applied to this
    exact role; their absence on SLC10A1 is a gap, not a convention.

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