ICY1 (YMR195W) — curator notes

UniProt: Q04329 (ICY1_YEAST). Systematic name YMR195W. SGD: S000004808.
Standard name ICY1 = "Interacting with CYtoskeleton" (SGD nomenclature; the name
predates and is not backed by a demonstrated molecular function). 127 aa, 14.3 kDa.
This is an UNDERSTUDIED ("dark") gene: molecular function and biological process
are officially undetermined (GO ND).

Provenance of primary facts

• Function (indirect / genetic): PMID:14504216 and PMID:14504216. Interpretation: ICY1 overexpression is a high-copy suppressor
  of the petite-negative phenotype of mitochondrial-import mutants, and icy1Δ cells
  cannot survive loss of mtDNA (become petite-negative). This paper describes ICY1
  as a cytosolic protein. It does NOT assign a molecular function.
• Subcellular location (GFP screen, HDA): PMID:14562095 Huh et al. global GFP
  localization — ICY1 is called to the vacuole membrane (SGD GO:0000329
  fungal-type vacuole membrane; UniProt "Vacuole membrane; Peripheral membrane
  protein"). Note the abstract is method-level; the ICY1 call is from the dataset.
  There is thus a localization discrepancy in the literature: cytosolic (14504216)
  vs. vacuole membrane (14562095). Both are recorded; neither pins a mechanism.
• Disruption phenotype: UniProt records "Invasive growth defect with elongated
  cell morphology" citing PMID:12673624 (Suzuki et al., transposon screen in a
  Sigma1278b pseudohyphal strain). The abstract is a general screen description and
  does not name ICY1; the ICY1-specific phenotype is in the full-text tables (curator
  read full text — do not overrule).
• Induction: PMID:15843968 ICY1 is induced by amino acid starvation
  (adhesion-inducing conditions). Abstract: ["adhesion can be induced by starvation
  for amino acids, and depends on the transcriptional activator of the general amino
  acid control system, Gcn4p"] and ["Twenty-two novel genes were identified as
  inducible by amino acid starvation"]. ICY1 is among the induced set (full-text
  table). UniProt: "Induced by amino acids starvation."
• Abundance: PMID:14562106 ~4050 molecules/cell in log-phase SD medium
  (UniProt MISCELLANEOUS). Consistent with a real, moderately expressed protein.
• SGD description (verbatim): "Protein of unknown function; required for
  viability in rich media of cells lacking mitochondrial DNA; mutants have an
  invasive growth defect with elongated morphology; induced by amino acid
  starvation." (yeastgenome.org locus S000004808).

Orthology / paralogy

• SGD lists ICY1's paralog (from the whole-genome duplication) as ATG41 /
  ICY2 (YPL250C), which functions in autophagosome formation. However, Icy1 has
  only low sequence similarity to Atg41/Icy2, and — unlike icy2Δ — icy1Δ does
  NOT show an autophagy defect. So the autophagy role of the paralog cannot be
  transferred to ICY1. (yeastgenome.org; Atg41 autophagy paper PMID via search.)
• No InterPro / Pfam / PANTHER / SUPFAM / PROSITE / SMART family is assigned in the
  UniProt record (checked: none). No transmembrane segment, no signal peptide, no
  coiled-coil, no recognizable catalytic motif. OrthoDB cluster 4033322at2759,
  HOGENOM CLU_149528_0_0_1 — small, fungal-restricted grouping.

Inline domain / sequence reasoning (done inline, no sub-agent)

Sequence (127 aa):
MSSNYATPLDDEVFPLSFANYQFTEHVSLGEHYSLNTSEDAKYNNLNGPFVVPRDTGKFDLNTSSASDETVFSLDNPQENNYKHQAMNNVQDCRMAVAAKTTQSCDKLTDLYANAAQQNYRLWLSSF

• Composition: Asn-rich (N 11.0%), Ser 10.2%, Thr 7.1%; net acidic (D+E 16 vs K+R 8);
  only 2 Cys, 1 Trp. This bias (Asn/Ser/Thr-rich, acidic, low aromatic/Cys) is
  typical of an intrinsically disordered / low-complexity small protein rather than
  a globular enzyme.
• No PROSITE-style catalytic signature is apparent by eye; the "MAVAAK" / "CDKLTD"
  stretches are not diagnostic motifs. UniProt annotates the whole chain as a single
  feature (PRO_0000203325) with no domains.
• The "Membrane / Vacuole; Peripheral membrane protein" keywords derive purely from
  the GFP localization; there is no hydrophobic membrane anchor in the sequence, so
  any membrane association is peripheral (consistent with the SubCell IEA).

KNOWN vs NOT-known summary

KNOWN (evidence-supported):
- Small (127 aa) fungal protein, moderately abundant (~4050 molecules/cell).
- Genetic role linked to survival of mtDNA-less (rho0) cells: high-copy suppressor
of petite-negativity in import mutants; icy1Δ is petite-negative PMID:14504216.
- Localizes to vacuole membrane in a genome-wide GFP screen PMID:14562095;
described as cytosolic in PMID:14504216 — location not fully settled.
- icy1Δ: invasive-growth defect with elongated morphology PMID:12673624; SGD also
lists abnormal vacuolar morphology, petite-negative, decreased growth.
- Transcriptionally induced by amino-acid starvation (Gcn4-linked context)
PMID:15843968.

NOT known (knowledge gaps — the real deliverable):
- Molecular function: NO biochemical activity, ligand, or catalytic role known
(GO MF = ND). No enzymatic motif; likely non-enzymatic. The "cytoskeleton
interaction" implied by the ICY1 name is not substantiated by any cited
molecular-interaction evidence I could verify.
- Biological process: the mtDNA-survival and invasive-growth phenotypes are
genetic/indirect; the direct pathway ICY1 acts in is undefined (GO BP = ND).
- Whether the vacuole-membrane localization is functionally meaningful or the
cytosolic pool is the active one is unresolved.
- Direct binding partners / whether it truly "interacts with the cytoskeleton" —
unverified in the sources available here.

Curation plan

• 4 GOA annotations. Localization terms (GO:0005774 IEA SubCell; GO:0000329 HDA)
  are supported by the GFP screen → keep. The vacuole-membrane call is the only
  positive experimental localization; keep as non-core (localization, not function).
• ND root terms (GO:0003674, GO:0008150) are placeholders indicating "no data";
  keep as-is (standard ND handling), do not invent MF/BP.
• core_functions: minimal/empty — no defensible molecular function to assert.
• knowledge_gaps: REQUIRED, primary deliverable (unknown MF, BP, mechanism of the
  petite-negative/invasive-growth phenotypes, reality of cytoskeleton interaction).