BIT2 (YBR270C) curation notes

Journal-style working notes for the AI GO-annotation review of Saccharomyces cerevisiae BIT2.
Provenance is recorded inline as [PMID:xxxx "verbatim supporting text"] or [source "..."].
BIT2-specific evidence is kept strictly separate from evidence about its paralog BIT61.

Identity (from UniProt P38346 / SGD S000000474)

Family / domain (inline domain analysis of the UniProt record)

KNOWN about BIT2 specifically (BIT2, not BIT61)

  1. BIT2 is a subunit of TORC2 (part of the TOR complex 2).
  2. GOA: GO:0031932 TORC2 complex, IDA, PMID:15689497, assigned by SGD (part_of). This is the
    experimental anchor for complex membership.
  3. The TORC2 subunit inventory in the cryo-EM paper explicitly names BIT2 as an alternative
    paralog subunit: PMID:29170376. NOTE: TORC2 contains Bit61 or Bit2 — the two paralogs are alternative,
    largely interchangeable accessory subunits of the same complex.
  4. BIT2 physically interacts with TORC2 components / effectors.
  5. UniProt SUBUNIT: "Interacts with the target of rapamycin complex 2 (TORC2) subunit TSC11 and
    the TORC2 effectors SLM1 and SLM2." {ECO:0000269|PubMed:11283351, ECO:0000269|PubMed:15689497}.
  6. These are the physical-interaction data (Ito et al. 2001 genome-wide two-hybrid PMID:11283351;
    Fadri et al. 2005 PMID:15689497) that place BIT2 in the TORC2/Slm1-Slm2 interaction network.
  7. CAUTION: PMID:15689497 is cached abstract-only (full_text_available: false); its abstract
    foregrounds Slm1/Slm2 binding Avo2 and Bit61 PMID:15689497. The BIT2 IDA to
    TORC2 complex is attributed by the SGD curator to this paper, so the BIT2-specific data are in
    the full text / figures that I cannot see. Per project rules I do NOT remove or downgrade the
    experimental IDA on the basis that the abstract names the paralog.
  8. Non-essential; viable null. bit2Δ is viable in S288C; high-throughput phenotyping reports
    decreased resistance to oxidative stress and to a farnesyltransferase inhibitor (SGD phenotype
    summary, high-throughput screens) [https://yeastgenome.org/locus/S000000474]. No strong,
    specific single-mutant growth phenotype is documented, consistent with paralog redundancy with
    BIT61.

KNOWN about the paralog BIT61 (kept separate — do NOT attribute to BIT2)

NOT known about BIT2 (the knowledge gaps)

  1. BIT2's specific molecular activity within TORC2 is undefined. The Bit61/PRR5 (HbrB) domain
    has no catalytic activity; BIT2 is an accessory/regulatory subunit whose molecular contribution
    (does it modulate substrate selection? complex stability? localization? effector, e.g. Slm1/Slm2,
    engagement?) has not been demonstrated for BIT2 specifically. GOA already flags this: the SGD MF
    annotation is GO:0003674 molecular_function ND (no data).
  2. BIT2's non-redundant function vs BIT61 is unknown. TORC2 contains "Bit61 or its paralog Bit2";
    whether the two paralogs are functionally distinct (differential expression, condition-specific
    incorporation, distinct effector bias) or fully redundant is not established. No bit2Δ bit61Δ
    double-mutant phenotype is annotated at SGD.
  3. No strong single-mutant loss-of-function phenotype pins down a BIT2-specific biological role;
    the reported phenotypes are high-throughput sensitivities (oxidative stress; farnesyltransferase
    inhibitor), not a mechanistic assignment.

GOA annotations to review (7 rows in BIT2-goa.tsv)

  1. GO:0007163 establishment or maintenance of cell polarity — IBA (GO_REF:0000033), involved_in.
    Phylogenetic (IBA). TORC2/Slm-actin axis does regulate polarized growth/actin, so this is
    plausible at the family level but is a downstream/process-level inference, not BIT2-specific
    experimental data. → KEEP_AS_NON_CORE (family/process-level, not core BIT2 activity).
  2. GO:0019887 protein kinase regulator activity — IBA (GO_REF:0000033), enables. IBA-projected MF.
    BIT2 as a TORC2 accessory subunit plausibly contributes to regulating the Tor2 kinase, but there
    is no BIT2 experimental MF; "regulator of the kinase" via being part of the complex is the family
    rationale. This is the least uninformative MF available. → KEEP_AS_NON_CORE (IBA family MF; not an
    independently demonstrated BIT2 activity; better captured as contributes_to at the complex level).
  3. GO:0031932 TORC2 complex — IBA (GO_REF:0000033), part_of. → ACCEPT (redundant with the IDA row
    but phylogenetically well-supported; core).
  4. GO:0038203 TORC2 signaling — IBA (GO_REF:0000033), involved_in. → ACCEPT/KEEP (core BP; TORC2
    membership implies participation in TORC2 signaling).
  5. GO:0031932 TORC2 complex — IDA, PMID:15689497, part_of. → ACCEPT (experimental anchor;
    core). Defer to SGD curator; do not REMOVE despite abstract-only cache foregrounding Bit61.
  6. GO:0038203 TORC2 signaling — IC (inferred from GO:0031932 complex membership),
    PMID:15689497, involved_in. → ACCEPT (IC directly from the experimental complex membership; core).
  7. GO:0003674 molecular_function — ND (GO_REF:0000015), enables. Root MF, no data. → ACCEPT/KEEP
    (honestly reflects that BIT2's specific MF is undetermined — the MF-dark gap; this is the correct
    use of ND, not a defect).

Core function synthesis

Deep-research provider status

Automated deep research was attempted twice via just deep-research-falcon yeast BIT2 --fallback perplexity-lite. Both attempts failed: the falcon provider timed out/was killed
(exit 143/144) and the perplexity-lite fallback returned HTTP 401 (API quota exceeded). No
-deep-research-{provider}.md file was produced, and none was fabricated. This review is
therefore grounded directly in the UniProt record (P38346), the GOA TSV, the cached primary
literature (PMID:15689497, PMID:11283351, PMID:29170376), the PANTHER/InterPro family record
(PTHR32428 / IPR013745 / PF08539), and the SGD locus page — all cited with provenance above.

References gathered / cached