SLC3A1 review notes

Research provenance

Falcon deep research was attempted and failed with HTTP 402. The configured
Perplexity-lite fallback was then attempted and failed with HTTP 401 because the
API quota was unavailable. No provider-named output was retained. The review
therefore uses the reviewed UniProt Q07837 record, the complete local GOA seed,
official QuickGO term definitions, the three Reactome records in the seed, nine
cached primary publications, and the manual synthesis in
SLC3A1-deep-research-manual.md.

The six publications fetched from the GOA seed were all inspected. Three
additional primary papers were cached and read because they resolve the key
curation boundary: PMID:10588648 identifies SLC7A9 as the catalytic subunit,
PMID:16825196 establishes rBAT-dependent oligomerization, and PMID:9987991 is
the rat source underlying the vacuolar-membrane transfer.

Core biological interpretation

SLC3A1 encodes rBAT, the type II glycoprotein heavy chain of an apical
heteromeric amino-acid transporter. It forms a disulfide-linked heterodimer with
SLC7A9. Native human kidney brush-border membranes contain the complex
PMID:12167606,
and the complex accounts for essentially all apical cystine reabsorption in the
studied proximal-tubule context PMID:12167606.

The heavy/light-chain distinction is decisive for reviewing the old transporter
molecular-function annotations. SLC7A9 is the catalytic subunit
PMID:10588648.
The heavy chain instead supports trafficking and maturation
PMID:32817565.
SLC3A1 is therefore involved in cystine and dibasic-amino-acid transport and
renal absorption, but it does not independently enable the amino-acid
transmembrane transporter activity. The review represents the direct function
as transporter activator activity and the complex-level transporter function as
contributes_to_molecular_function.

Complex architecture and the extracellular domain

The rBAT-SLC7A9 heterodimer is the minimal functional unit, while rBAT-rBAT
contacts assemble two heterodimers into a heterotetramer. The title and abstract
of PMID:16825196 explicitly state that the heavy chain dictates oligomerization
and that "a single heterodimer is the functional unit." Cryo-EM independently
resolves rBAT-mediated dimerization PMID:32494597.

The large extracellular rBAT region has an alpha-amylase-like fold, which drives
an InterPro annotation to carbohydrate metabolic process. That inference is
experimentally contradicted: the purified complex had no detectable
alpha-glucosidase activity PMID:32494597.
The carbohydrate-process IEA is therefore removed rather than merely downgraded.

Localization boundaries

Brush-border, apical-plasma-membrane, plasma-membrane, and membrane annotations
all agree with the established epithelial site and are accepted. Urinary-exosome
detection comes from a large proteomic survey whose local abstract does not expose
the SLC3A1 peptide result PMID:19056867.
It is left undecided rather than treated as a verified functional exosome assignment.

The vacuolar-membrane transfer traces to rat forebrain immunoelectron microscopy
PMID:9987991.
Because the source-side experiment is explicit, the human IEA is kept as non-core;
its relevance to endogenous human neuronal biology remains unresolved.

Annotation decisions

Annotation group Decision
brush border membrane (4 evidence groups) ACCEPT
amino acid transport (3 evidence groups) ACCEPT
amino acid transmembrane transport ACCEPT as a process contribution
plasma membrane (7 evidence groups) ACCEPT
carbohydrate metabolic process REMOVE
membrane (2 evidence groups) ACCEPT
apical plasma membrane (2 evidence groups) ACCEPT
basic amino acid transmembrane transport ACCEPT as a process contribution
protein binding (2 evidence groups) MODIFY to protein heterodimerization activity
vacuolar membrane KEEP_AS_NON_CORE
protein-containing complex binding MODIFY to protein heterodimerization activity
transmembrane transporter complex MODIFY to amino acid transport complex
protein heterodimerization activity ACCEPT
extracellular exosome UNDECIDED
amino acid transmembrane transporter activity MODIFY to transporter activator activity
basic amino acid transmembrane transporter activity MODIFY to transporter activator activity
L-cystine transmembrane transporter activity MODIFY to transporter activator activity
basic amino acid transport ACCEPT
L-cystine transport ACCEPT
renal amino acid absorption NEW

Duplicate GO terms use consistent actions. No generic protein-binding annotation
is retained, and no experimental annotation is removed on the basis of missing
full text.

Open questions