spa1 (SPBC577.14c) — S. pombe ornithine decarboxylase antizyme — review notes
Deep-research note: the automated deep-research job
(scripts/deep_research_wrapper.py SCHPO spa1 falcon --fallback perplexity-lite)
produced no output and did not create a report file after ~25 min; it was stopped.
This review is therefore grounded directly in the UniProt record (Q9USQ5), the GOA
annotations, the PomBase API record, verified GO term definitions (QuickGO), and the
cached primary literature (PMID:10775274 full text; PMID:10871270 abstract). No
-deep-research-*.md file was fabricated.
Identity (verified — NOT the mammalian SPA1 GAP)
- UniProt Q9USQ5 (
OAZ_SCHPO), 226 aa; gene spa1 (synonym spa); systematic SPBC577.14c; NCBI taxon 284812.
- RecName: Ornithine decarboxylase antizyme (ODC-Az) [spa1-uniprot.txt lines 6–8].
- Family: ODC antizyme family (
ECO:0000305) [spa1-uniprot.txt line 83]. Domain signatures: Pfam PF02100 (ODC_AZ), InterPro IPR002993 (ODC_AZ) + IPR038581 (ODC_AZ_sf); Gene3D 3.40.630.60; SUPFAM SSF55729 (Acyl-CoA N-acyltransferase / NAT fold) [spa1-uniprot.txt lines 115–122]. The single antizyme domain spans essentially the whole ORF2-encoded chain.
- PANTHER family PTHR10279 ORNITHINE DECARBOXYLASE ANTIZYME (subfamily SF10) — the source of the IBA annotations [spa1-uniprot.txt lines 119–120].
- This is the fission-yeast antizyme, unrelated to human/mouse SPA1 (SIPA1) Rap GTPase-activating protein. Domain analysis (antizyme domain only; no GAP/RapGAP domain, no GTPase signature) confirms it is a bona fide OAZ-family protein, matching the name.
Provenance for function — this gene is directly, experimentally characterized
Despite being an understudied ORF, spa1 was functionally characterized in a dedicated primary
paper:
PMID:10775274 (Ivanov, Matsufuji, Murakami, Gesteland, Atkins, EMBO J 2000, "Conservation of
polyamine regulation by translational frameshifting from yeast to mammals"). Full text cached.
Key experimental results on the S. pombe gene itself (named "SPA" in the paper):
- ODC inhibitory activity (direct assay). Recombinant GST–SPA fusion protein expressed in
E. coli and purified inhibits S. pombe ODC in vitro; GST alone does not
PMID:10775274. → supports GO:0008073 ornithine decarboxylase inhibitor activity (experimental, IDA-grade).
- Negative regulation of polyamine biosynthesis (loss-of-function genetics). Δspa knockouts
accumulate putrescine, spermidine and cadaverine, most dramatically in stationary phase (up to
~40× putrescine)
PMID:10775274.
Overexpression depletes all polyamines
PMID:10775274.
→ SPA is a negative regulator of polyamine biosynthesis. The authors conclude "SPA is the
primary regulator of ODC activity in S.pombe"
PMID:10775274.
- Autoregulatory +1 ribosomal frameshifting. Expression of full-length SPA requires a
polyamine-responsive +1 frameshift between ORF1 and ORF2
PMID:10775274;
frameshift efficiency rises with spermidine
PMID:10775274
and falls when polyamines are depleted by SPA overexpression, closing the autoregulatory loop
PMID:10775274.
UniProt records the frameshift between Ser-67 and Glu-68 [spa1-uniprot.txt lines 76–82].
- Deletion phenotype. Δspa is viable with no overt growth/morphology/mating defect
PMID:10775274.
PMID:10871270 (Zhu, Karplus, Grate, Coffino, Bioinformatics 2000). HMM-based identification of
the S. pombe antizyme homolog; abstract-only cached. Establishes the sequence/family assignment
and the conserved frameshift signal
PMID:10871270.
Note: sequence identity to metazoan antizymes is low (~10% identity / ~24% similarity per
PMID:10775274; 18–22% in the most conserved C-terminal regions per PMID:10871270).
Mechanism by orthology (mammalian AZ1, UniProt Q02803)
UniProt propagates by similarity (ISS from Q02803 = rat AZ1): antizyme binds ODC monomers,
sterically blocking assembly of the active ODC homodimer, and targets ODC monomers for
ubiquitin-independent degradation by the 26S proteasome
[spa1-uniprot.txt lines 67–75 "Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimer, and targets the monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome"].
The Ivanov paper directly demonstrated ODC inhibition by SPA but did NOT test the
degradation-targeting or monomer-binding mechanism in S. pombe — that specific mechanistic step
is inferred from the mammalian ortholog, not shown for spa1.
Localization — KNOWN vs NOT known
- No experimental localization exists for spa1. PomBase curated CC is only GO:0005829
cytosol, and it derives from GO_REF:0000051 (S. pombe keyword mapping / NAS) — an
inference from the antizyme keyword, not from microscopy (verified via PomBase API: the CC
annotation for SPBC577.14c cites GO_REF:0000051).
- The GOA nucleus (GO:0005634) and cytoplasm (GO:0005737) annotations are IBA
(GO_REF:0000033), propagated from the PANTHER antizyme tree (mammalian AZ1/AZ2 shuttle between
cytoplasm and nucleus). Neither is experimentally supported in S. pombe.
- The Ivanov paper does not report where SPA acts in the cell.
Biological role and phenotypes (context; not GO-review targets)
- Core role: feedback control of intracellular polyamine (putrescine/spermidine) levels by
inhibiting ODC (the rate-limiting biosynthetic enzyme), sensed via polyamine-dependent
frameshifting. spa1 appears to be the principal negative regulator of ODC in S. pombe.
- PomBase records many single-locus deletion phenotypes from high-throughput screens (verified via
PomBase API): viable vegetative population (FYPO:0002060; PMID:20473289, PMID:23697806),
loss of viability in stationary phase (FYPO:0000245; PMID:34250083), sensitivity to hydroxyurea
(FYPO:0000088; PMID:23173672), tert-butyl hydroperoxide (FYPO:0000797), NaCl (FYPO:0005889), and
others (mostly PMID:37787768). These are consistent with polyamine dysregulation having
pleiotropic, condition-dependent effects but do not by themselves define new GO functions.
Annotation-review plan
| Term |
Aspect |
Ev |
Ref |
Planned action |
Rationale |
| GO:0008073 ornithine decarboxylase inhibitor activity |
MF |
IBA |
GO_REF:0000033 |
ACCEPT (core) |
Correct; also directly demonstrated in PMID:10775274 |
| GO:0008073 ornithine decarboxylase inhibitor activity |
MF |
IEA |
GO_REF:0000002 (InterPro IPR002993) |
ACCEPT (core) |
Same term, domain-supported; redundant but correct |
| GO:1901305 negative regulation of spermidine biosynthetic process |
BP |
NAS |
GO_REF:0000051 |
KEEP_AS_NON_CORE (or MODIFY) |
Real (Δspa raises spermidine) but overly specific; broader "negative regulation of polyamine biosynthetic process" (GO:0170066, which UniProt/PomBase now use as TAS) better captures the function |
| GO:0005829 cytosol |
CC |
NAS |
GO_REF:0000051 |
KEEP_AS_NON_CORE |
Plausible but keyword-inferred, no experimental localization |
| GO:0005634 nucleus |
CC |
IBA |
GO_REF:0000033 |
MARK_AS_OVER_ANNOTATED / REMOVE |
Propagated from mammalian AZ nuclear shuttling; no evidence in S. pombe |
| GO:0005737 cytoplasm |
CC |
IBA |
GO_REF:0000033 |
KEEP_AS_NON_CORE |
Broad, consistent with cytosolic action; uninformative but not wrong |
Note UniProt DR lines show PomBase now curates GO:0170066 negative regulation of polyamine
biosynthetic process (TAS) [spa1-uniprot.txt line 114], the more appropriate parent of the
GOA GO:1901305 spermidine-specific term.
Knowledge gaps (for the review)
- Localization is unknown (CC-dark): no microscopy has placed spa1 in a compartment; all CC
annotations are inference/propagation.
- Mechanism in S. pombe (residual sub-gap): whether spa1 targets S. pombe ODC for
ubiquitin-independent proteasomal degradation (as mammalian AZ1 does) vs. only steric
inhibition of ODC dimerization is not established in fission yeast; only ODC inhibition was
assayed.
- Physiological role of polyamine feedback (biology): why the antizyme frameshift circuit is
so deeply conserved yet dispensable for growth is explicitly unresolved by the authors
PMID:10775274.
- Second target (polyamine transporter)? In mammals AZ also inhibits the polyamine
transporter; the Ivanov paper raised but did not resolve whether SPA does so in S. pombe
PMID:10775274.