acn1 (SPBC3H7.05c / O74380) — curation notes

Fission yeast (Schizosaccharomyces pombe 972 / ATCC 24843). UniProt entry name YNV5_SCHPO.
PomBase standard name acn1; systematic name SPBC3H7.05c; UniProt accession O74380.

Summary / bottom line

acn1 is an understudied ("conserved unknown") gene encoding a polytopic
integral membrane protein of the membrane-bound O-acyltransferase (MBOAT)
superfamily. PomBase characterisation status is conserved unknown and UniProt
PE level is 4: Predicted. There is no dedicated functional/biochemical study
of acn1; essentially all annotations are either sequence/domain-based inference or
high-throughput screen phenotypes. The confident statements one can make are about
its domain architecture and localization; its specific molecular substrate,
biological process, and physiological role remain unknown.

Identity and provenance

• PomBase gene page (API www.pombase.org/api/v1/dataset/latest/data/gene/SPBC3H7.05c):
• name: acn1, product: "membrane bound O-Acyl transferase (MBOAT) family",
  characterisation_status: conserved unknown, deletion_viability: viable,
  uniprot_identifier: O74380.
• name_descriptions: ["ACetylation of Hy8Z (Nitrogen Signaling Factor (NSF)"] —
  i.e. the symbol acn1 was coined from a proposed "ACetylation of Nsf"
  hypothesis; this is a name derivation, not experimentally established
  function.
• Taxonomic distribution flags: conserved in eukaryotes, conserved in fungi,
  no apparent S. cerevisiae ortholog (PBO:0000055).

Domain / sequence analysis (from UniProt O74380 record, inline)

• 357 aa; 9 predicted TM helices (TRANSMEM 13-33, 44-64, 72-92, 148-168, 181-201,
  203-223, 266-286, 293-313, 327-347) — a multi-pass integral membrane protein.
• InterPro IPR032805 (Wax_synthase_dom) / Pfam PF13813 (MBOAT_2). This is the
  wax-synthase branch of the MBOAT superfamily (distinct Pfam clan member from the
  "core" MBOAT PF03062). Pfam PF13813 = "Membrane bound O-acyl transferase family";
  associated activity is O-acyltransferase (verified via InterPro API PF13813).
• MBOAT enzymes carry a conserved catalytic His in a hydrophobic stretch and an
  invariant upstream Asn/His. In acn1 the His residues fall at 65/66, 250, 287, 326;
  H287 sits in the conserved "...ALFHDFAY..." block (the LYHDFAF fingerprint that
  UniProt's OMA record captured), and H250 in "...WSRDWH...". Presence of these
  His/Asn residues is consistent with a retained catalytic capacity but does not
  by itself prove activity or identify a substrate. [inline sequence inspection]

Existing GO annotations (from acn1-goa.tsv; 4 GOA lines)

1. GO:0031966 mitochondrial membrane — IEA, GO_REF:0000044 (UniProtKB-SubCell
   mapping SL-0171). Derived from the UniProt subcellular-location statement
   "Mitochondrion membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}".
   ECO:0000305 = curator inference (not direct assay). The primary evidence for a
   mitochondrial localization is the ORFeome GFP screen PMID:16823372.
2. GO:0005575 cellular_component — ND, GO_REF:0000015 (root "no data" placeholder).
3. GO:0008150 biological_process — ND, GO_REF:0000015 (root "no data" placeholder).
4. GO:0016747 acyltransferase activity, transferring groups other than amino-acyl
   groups — ISS, GO_REF:0000024, WITH/FROM: PomBase:SPAC24H6.01c. Transferred by
   curator judgment of sequence similarity from gup1 (SPAC24H6.01c, Q09758), an
   MBOAT (product "membrane bound O-acyltransferase, MBOAT Gup1"; annotated to
   GO:0006506 GPI anchor biosynthetic process). NOTE: gup1 uses Pfam PF03062
   (MBOAT_fam) whereas acn1 uses PF13813 (Wax_synthase_dom) — related superfamily,
   different subfamily; the ISS supports family-level acyltransferase activity but
   NOT gup1's specific GPI-anchor function.

Also present in the UniProt DR block (not in GOA TSV): GO:0005739 mitochondrion
HDA:PomBase (from the ORFeome localization dataset), and the now-obsolete
GO:0008374 O-acyltransferase (superseded by GO:0016747). Verified GO:0008374 is
obsolete via QuickGO.

Localization evidence

• Mitochondrion / mitochondrial membrane: ORFeome-wide GFP localization study
  PMID:16823372 underlies the HDA mitochondrion call and
  the UniProt SubCell statement. This is a genome-scale screen (moderate confidence
  for any single protein); a mitochondrial membrane MBOAT is somewhat atypical (most
  characterized MBOATs are ER/Golgi/plasma-membrane), so localization deserves a
  caveat but is the only localization datum available.

Phenotype data (all high-throughput or overexpression; PomBase FYPO)

• PMID:37787768 (Bähler lab broad phenomics / machine-learning profiling of fission
  yeast proteins) contributes ~20 FYPO annotations for acn1delta, e.g. multidrug
  resistance/sensitivity (resistance to diamide, KCl, terbinafine, tert-butyl
  hydroperoxide; sensitivity to cadmium, rapamycin, torin1, tunicamycin, brefeldin A,
  vanadate, X-rays), and nitrogen/carbon-source growth changes (FYPO:0009091 decreased
  growth on lysine+proline N source; FYPO:0009076 increased growth on sucrose). These
  are pleiotropic screen hits, not evidence of a specific molecular function.
• PMID:23695302 (fission-yeast TF overexpression analysis) contributes low-throughput
  overexpression phenotypes (FYPO:0001406 increased septum thickness; multiseptate /
  mono-septate binucleate-anucleate cells). Overexpression phenotypes are weak evidence
  for endogenous function.
• PMID:40424131 (Formation of giant ER sheets by pentadecanoic acid causes
  lipotoxicity in fission yeast, PNAS 2025) contributes FYPO:0010042 "normal growth on
  pentadecanoic acid" for acn1delta — i.e. acn1 was screened in a lipotoxicity study
  and its deletion did not alter C15:0 sensitivity (a negative result). acn1 is
  not discussed in that paper's body text.

KNOWN vs NOT-known

KNOWN (well-supported):
- It is a polytopic integral membrane protein (9 TM helices; UniProt/DeepTMHMM).
- It belongs to the MBOAT superfamily, wax-synthase (PF13813/IPR032805) branch.
- It localizes to mitochondria / mitochondrial membrane (ORFeome GFP screen; single
moderate-confidence line of evidence).
- Deletion is viable with no gross morphology defect (FYPO:0002177), consistent
with a non-essential gene.
- It has no apparent S. cerevisiae ortholog but is conserved across fungi/eukaryotes.

NOT known (knowledge gaps):
- Molecular function / catalytic activity: whether acn1 is a catalytically active
acyltransferase, and if so its acyl-donor and acceptor substrates, are unknown. The
MF annotation is ISS-from-paralog at the general "acyltransferase, non-amino-acyl"
level only.
- Biological process: unknown. The "acn1 = ACetylation of Nsf" name is a hypothesis,
not established. No BP annotation with experimental support exists.
- Physiological role / pathway: unknown. Phenotypes are broad pleiotropic
screen/overexpression hits that do not converge on a mechanism.
- Localization detail: sub-mitochondrial location and topology unverified beyond a
single genome-scale GFP dataset; a mitochondrial-membrane MBOAT is atypical.
- Direct interactors / regulation: none experimentally established for function.

Candidate MF for core_functions

• GO:0016747 (acyltransferase activity, transferring groups other than amino-acyl
  groups) is the most specific defensible MF: it is the current (non-obsolete) term,
  it is family/domain-appropriate for an MBOAT, and it is what GOA already carries via
  ISS. Anything more specific (wax-ester synthase, DGAT, GPI-anchor acyltransferase,
  protein-serine O-palmitoleoyltransferase, etc.) would be an over-annotation given no
  substrate data. core_functions should carry at most this one MF with an explicit
  low-confidence/uncertainty note, plus the mitochondrial-membrane location; the primary
  deliverable is the knowledge_gaps section.

Falcon deep research (acn1-deep-research-falcon.md, Edison, 26 citations)

The falcon report (completed 2026-07-06, 1659 s) independently reached the same
conclusion and adds useful comparative context. Key points (all secondary/inferential,
about the MBOAT family, NOT direct acn1 data):
- No primary research article has characterized acn1/SPBC3H7.05c function, activity, or
role; all inference is domain/homology-based. (converges with my analysis.)
- MBOAT superfamily = integral-membrane acyltransferases with conserved catalytic His
(in a TM stretch) + upstream Asn; three functional subgroups (sterol/DAG acylation
e.g. ACAT/DGAT1; protein/peptide acylation e.g. PORCN/HHAT/GOAT; lyso-phospholipid
re-acylation e.g. LPCAT/MBOAT7). The wax-synthase (WS) branch acylates fatty
alcohols with fatty-acyl-CoA to make wax esters, and DGAT1-type members make TAG.
- Predicted acn1 activity: acyl-CoA-dependent acyltransferase, most consistent with
wax-ester-synthase and/or DGAT1-type chemistry — but substrate is unknown.
- S. pombe neutral-lipid context: TAG synthesis is by dga1 (DGAT2 fold, structurally
UNRELATED to MBOAT) and plh1 (PDAT); sterol esterification by Are1/Are2 homologs
(Zhang et al. 2003, JBC). acn1 (MBOAT/DGAT1-type) is therefore a distinct enzyme
class and, if catalytically active, would be an additional/accessory acyltransferase.
- Predicted localization by MBOAT analogy: endoplasmic reticulum (DGAT1/ACAT are
ER-resident). NOTE this CONFLICTS with the only experimental localization datum for
acn1 (mitochondrion, ORFeome GFP screen PMID:16823372). This discrepancy is itself a
knowledge gap — the family prior says ER, the single S. pombe screen says mitochondrion.
- CAVEAT on the report: it treats "Wax_synthase_dom (IPR032805)" and "MBOAT_2 (PF13813)"
as two domains; they are the SAME domain (InterPro IPR032805 is the InterPro entry for
Pfam PF13813). Do not double-count. The falcon DOI citations are family reviews, not
acn1-specific; I will NOT cite them as supporting acn1 function directly.