SLC10A6 (SOAT) curation notes

UniProt: Q3KNW5 (SOAT_HUMAN), 377 aa, 7 transmembrane domains, glycosylated.
Gene: SLC10A6, synonym SOAT. Taxon: NCBITaxon:9606.

Deep research was not available in this container (Falcon returned HTTP 402,
OpenAI HTTP 401, perplexity not registered), so no -deep-research-*.md file was
generated. The literature synthesis below was assembled by hand from PubMed and
the cached publications/PMID_*.md records.

Literature synthesis

Core activity: sodium-coupled uptake of sulfated steroids

SOAT was cloned and characterized by Geyer and colleagues. In stably transfected
HEK293 cells it mediates sodium-dependent uptake of the three canonical steroid
sulfates with low-micromolar affinity
PMID:17491011.
UniProt records the symport stoichiometry as 2 Na+ per steroid sulfate
(e.g. Rhea:RHEA:71083 for estrone 3-sulfate).

The substrate spectrum was extended by LC-MS/MS-based transport assays to
17alpha-hydroxypregnenolone sulfate, 17beta-estradiol-17-sulfate, androsterone
sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate
and 5alpha-dihydrotestosterone sulfate, and the structural requirements were
defined PMID:28951227,
PMID:28951227 — note
that a second sulfate group abolishes recognition (17beta-estradiol-3,17-disulfate
is not transported).

Beta-estradiol-3-sulfate and androstenediol-3-sulfate were added as substrates in
the testis study PMID:23667501, and the
placental estriol precursor 16alpha-OH-DHEAS is a low-affinity substrate
PMID:24717977.

The current review of the field states the specificity plainly
PMID:37373074.

Bile acids: the decisive specificity question for this review

SOAT sits in the bile acid:sodium symporter (BASS, SLC10) family and is the
closest paralog of ASBT (48% identity), but the canonical bile acids are not
substrates PMID:17491011,
PMID:34079822.

Reactome itself makes the same point in the summary of the very reaction that
grounds its TAS annotations
[Reactome:R-HSA-433089 "Unlike the other SLC10A gene products, SOAT shows no
affinity for binding bile acids. However, SOAT is able to transport
sulpho-conjugated bile acids such as taurolithocholate 3-sulphate (Geyer J et al,
2007)."].

However, the bile-acid terms are not simply false for SOAT. The systematic
three-carrier comparison found that taurolithocholic acid — an unsulfated,
taurine-conjugated bile salt — is a sodium-dependent SOAT substrate, with Km
19.3 uM, comparable to NTCP (18.4 uM) and ASBT (5.9 uM)
PMID:34079822. The restriction is positional: additional
7'/12' hydroxylation abolishes it
PMID:34079822.

Crucially for reviewing the IBA rows, the authors explicitly leave the
evolutionary question open
PMID:34079822.

Consequence for the IBA node placement. The IBA rows for GO:0008508 and
GO:0015721 derive from PANTHER:PTN000040761, the node ancestral to the
Na+-dependent SLC10 clade (human SLC10A1/A2/A4/A6 all receive rows from it),
seeded by the rat descendants RGD:3681 (Slc10a1/Ntcp) and RGD:3682
(Slc10a2/Asbt). I did not find grounds to reject that node placement for
SLC10A6: SOAT retains sodium-coupled symport of a genuine bile salt (TLC), so
the inherited activity has been narrowed rather than lost, and the literature
states that whether TLC transport is ancestral or convergent cannot currently be
decided. The honest reading is therefore "retained but narrowed, and not the core
function" — i.e. KEEP_AS_NON_CORE, not REMOVE. What is wrong is only the
implication that this is what SOAT is for.

Localization

Sorting studies place the protein at the plasma membrane
PMID:37373074,
PMID:28743544.
In placenta, SOAT is at the apical (maternal-facing microvillous) membrane of
syncytiotrophoblasts and in vessel endothelium
PMID:24717977.
All functional assays are uptake assays on intact cells, which independently
require the carrier to be in the plasma membrane. UniProt records only the generic
Membrane location (multi-pass), consistent with the IEA GO:0016020 row.

Expression and physiology

Testis-dominant, with placenta and pancreas next
PMID:17491011. In testis the protein is
in germ cells (zygotene/pachytene spermatocytes, round spermatids), and expression
is reduced in disorders of spermatogenesis
PMID:23667501.

The proposed physiological role is delivery of circulating, biologically inert
steroid sulfates into target cells for intracrine reactivation by steroid
sulfatase. Note that the knockout does not support a required role in
reproduction
PMID:28743544, although
male knockouts have raised serum cholesterol sulfate
PMID:28743544.
This is the reason no spermatogenesis or hormone-biosynthesis process term is
proposed here.

A disease-relevant consequence of the transport activity: SOAT expression renders
breast cancer cells responsive to estrone-3-sulfate
PMID:30186172. This is a downstream consequence of substrate
uptake, not a separate SOAT activity, so it is not annotated.

Protein interactions

SOAT homo- and heterodimerizes within the SLC10 family
PMID:31256060. With NTCP it co-localizes and co-immunoprecipitates, but unlike
SLC10A4 it does not impair NTCP transport
PMID:22029531,
PMID:22029531.
This is targeted, informative interaction evidence — and it is not the source of
any GOA row. The 144 GO:0005515 protein binding rows all come from the HuRI
proteome-scale binary interactome map PMID:32296183, give no functional
information, and are removed under the repository's generic-protein-binding
policy. Removal is not a claim that any interaction is false.

Ontology work

Verified against OLS4 (ols4/api/ontologies/go/terms/...):

• GO:0008508 bile acid:sodium symporter activity — current. Definition is the
  symport reaction bile acid(out) + Na+(out) = bile acid(in) + Na+(in). Parents:
  GO:0005343 organic acid:sodium symporter activity, GO:0015125 bile acid
  transmembrane transporter activity, GO:0015355 secondary active monocarboxylate
  transmembrane transporter activity. The monocarboxylate parentage is one reason
  this term cannot represent steroid-sulfate symport.
• GO:0015721 bile acid and bile salt transport — current.
• GO:0043251 sodium-dependent organic anion transport — current; sole parent
  GO:0055085 transmembrane transport (so it is neither ancestor nor descendant of
  GO:0015721). This is the correct and best-available BP for SOAT.
• GO:0043252 sodium-independent organic anion transport — current (not applicable).
• GO:0015711 organic anion transport — obsolete.
• GO:0008514 organic anion transmembrane transporter activity — obsolete,
  term replaced by GO:0022857 transmembrane transporter activity (uninformative).
• GO:0005886 plasma membrane, GO:0016020 membrane — current.

Gap: there is no molecular-function term for sodium-coupled steroid-sulfate
symport. Searching GO via OLS for "steroid sulfate", "estrone sulfate" and
"organosulfate" returns only sulfotransferase/sulfatase activities and ChEBI
chemicals; the children of GO:0015370 solute:sodium symporter activity cover
amino acids, sugars, nucleosides, bile acids, monocarboxylates, taurine,
ascorbate, inositol, choline and inorganic ions, with nothing for sulfate esters
of steroids. A new term steroid sulfate:sodium symporter activity under
GO:0015370 is therefore proposed, and the core function uses
proposed_molecular_function rather than forcing GO:0008508.

Review decisions

No NEW annotation rows were added. The one genuine gap is a molecular function
with no GO term, which is raised as a proposed_new_terms entry instead.