MIH1 (YMR036C, UniProt P23748) curation notes

2026-09-25 — first full review

Sole budding-yeast Cdc25 homolog; MPI phosphatase family, rhodanese fold, PROSITE
rhodanese domain 261-373, active-site Cys320 (UniProt, by similarity). 554 aa,
63 kDa (the 1989 paper predicted 54 kDa from a partial/erroneous ORF).
PANTHER PTHR10828:SF17. PAINT nodes used in the IBA rows: PTN000089071 (G2/M
process node, MIH1 itself among the descendant evidences) and PTN000850864
(PTP activity / localisation node).
The repository module modules/g2_m_transition.yaml uses Mih1 as the
budding-yeast exemplar of the Cdc25 annoton.

Founding paper: MIH1 cloned as the gene counteracting fission-yeast wee1+ in
S. cerevisiae PMID:2649252; PMID:2649252.
The mih1 G2 delay is entirely Swe1-dependent PMID:8253069.
Reaction: Cdc28-pTyr19 -> Cdc28-Tyr19 PMID:16688214; PMID:21536748.
Not essential, unlike pombe cdc25 PMID:22918234.
Morphogenesis checkpoint: PMID:8930890; septin mutants
PMID:10805747; hsl1
mih1 and hsl7 mih1 double mutants inviable PMID:10805747; MIH1 overexpression suppresses GAL-SWE1 lethality
PMID:9744879.
Regulation: hyperphosphorylated in interphase, dephosphorylated at mitotic entry
PMID:22918234; PP2A-Cdc55 is the phosphatase
PMID:23861665; cdc55 / zds1
zds2 mutants keep Mih1 hyperphosphorylated and are rescued by MIH1 overexpression
PMID:21536748. Cdc5 targets Mih1
PMID:20126259. Mck1 co-precipitates with
Mih1 PMID:22918234.
Spindle: PMID:30072442; PMID:30072442. Abstract only cached.
Meiosis (2026, full text cached): PMID:41927924; PMID:41927924;
localisation: PMID:41927924.

Kennedy et al. 2016 Genetics 202:903 "Redundant Regulation of Cdk1 Tyrosine
Dephosphorylation in Saccharomyces cerevisiae" — PMID:26715668. Per the falcon
deep-research summary: purified Mih1 directly dephosphorylates Swe1-phosphorylated
Cdc28-Clb2 in vitro; mih1Δ retains ~65% mitotic Cdk1 activity; Ptp1 and PP2A-Rts1
are redundant Tyr19 phosphatases; mih1Δ ptp1Δ rts1Δ is lethal unless SWE1 is
deleted. This is the direct-assay evidence that would justify upgrading the SGD
ISS PTP row to IDA.
Keaton et al. 2008 Mol Biol Cell 19:4006 "Nucleocytoplasmic trafficking of G2/M
regulators in yeast" — PMID:18562688. Mih1-12Myc mostly cytoplasmic; nuclear in
~75% of post-anaphase cells; K31-33A blocks nuclear entry, cytoplasm-restricted
Mih1 is less effective, SV40 NLS rescues.
Pal, Paraz and Kellogg 2008 J Cell Biol "Regulation of Mih1/Cdc25 by protein
phosphatase 2A and casein kinase 1" — PMID:18316413. PP2A-Cdc55 dephosphorylates
Mih1 at mitotic entry; CK1 (Yck1/2) phosphorylates it.
Harvey et al. 2011 Mol Biol Cell "A phosphatase threshold sets the level of Cdk1
activity in early mitosis in budding yeast" — PMID:21849476.
Galli et al. 2021 Front Cell Dev Biol "Haspin Modulates the G2/M Transition Delay
in Response to Polarization Failures in Budding Yeast" — PMID:33585466. Alk1 loss
allows premature nuclear division in cdc24-1; MIH1 deletion restores the delay.

All GO:0004725 rows (IBA, IEA, two ISS): ACCEPT. Core MF, directly demonstrated.
GO:0000086 IBA + IMP and GO:0010971 IBA: ACCEPT (core process).
GO:1902751 IEA (InterPro2GO): MODIFY -> GO:0010971, mirroring the SCHPO cdc25
review; the generic parent adds nothing.
Nucleus / cytoplasm (HDA x2, IBA x2): ACCEPT. Shuttling enzyme; both pools
functional (Keaton 2008), nuclear pool more effective.
GO:0051231 spindle elongation IMP (acts_upstream_of_or_within): KEEP_AS_NON_CORE;
genuine phenotype, indirect via Cdc28/Bik1; GO:0000022 would be the more precise
mitotic child if SGD refines.
GO:0110032 meiotic G2/MI IBA: KEEP_AS_NON_CORE; now backed by direct
S. cerevisiae evidence (PMID:41927924), same activity deployed in meiosis.
No NEW terms. Considered "morphogenesis checkpoint" type terms (Mih1 is the
dosage-sensitive output of the checkpoint), but Mih1 is the regulated effector
rather than a signalling component and SGD has not annotated it; raised in
suggested_questions/experiments instead.
No bare protein-binding IPI rows exist in GOA for MIH1, so the protein-binding
policy did not need to be applied.

Searched for 2024-2026 MIH1/YMR036C literature. The direct new paper remains
the 2026 meiotic prophase I study already incorporated as PMID:41927924; no
newer paper was found that changes the core Cdc28-Tyr19 phosphatase model.
Re-checked current PTHR10828 PAINT. PTN000089071 still carries
GO:0000086, GO:0010971, and GO:0110032; PTN000850864 still carries
GO:0004725, GO:0005634, and GO:0005737.
The existing IBA decisions stand. All MIH1 IBA rows are either core positive
controls or, for meiotic G2/MI, a genuine non-core deployment of the same
Cdc28-activating activity.