MCM4 (CDC54, YPR019W; UniProt P30665), Saccharomyces cerevisiae

2026-10-21 — Full re-review, independent of the ProtNLM2 predictions

Context: reviewed as the experimentally characterised reference for transfer to the
PTHR11630:SF66 (MCM4) subfamily, including Neurospora NCU02539. No ProtNLM2 output was
consulted.

Deep research

just deep-research-falcon yeast MCM4 --fallback perplexity-lite failed: falcon returned
"Failed to authenticate", and the perplexity-lite fallback returned HTTP 401 (insufficient
quota). There is no deep-research file. The review rests on the cached publications for the 31
GOA-cited PMIDs (14 with full text), the UniProt record and the PANTHER/PAINT data in
interpro/panther/PTHR11630/.

Evolutionary placement

• UniProt: PANTHER; PTHR11630:SF66; DNA REPLICATION LICENSING FACTOR MCM4, with the
  MCM_4 InterPro signature IPR008047 and a WHD_MCM4 Pfam domain.
• PAINT (PTHR11630-paint.tsv):
• PTN000179711 (MCM2-7 node): IBD for MCM complex, ssDNA binding (seeded by SGD
  S000006223 = this gene alone) and ssDNA helicase activity.
• PTN000179712: nucleus.
• PTN000179968 (Mcm4 subfamily node, taxon 2759): GO:0000727 BIR and GO:0006271 strand
  elongation, both seeded by this gene; GO:1902975 mitotic replication initiation, seeded by
  S. pombe cdc21.
• Not propagated at any node: pre-RC assembly (GO:0006267), origin binding (GO:0003688),
  premeiotic replication, four-way junction helicase and 3'-5' helicase. If these are
  transferred to orthologs, the omission should be treated as a deliberate PAINT decision.
• There are IRD (NOT) nodes for Drosophila and Deuterostomia branches. They do not affect
  yeast.

Experimentally established in S. cerevisiae (direct evidence)

• Subunit of Mcm2-7, reconstituted from recombinant subunits PMID:12480933.
• Loaded by ORC-Cdc6-Cdt1 onto origins as head-to-head double hexamers that encircle and slide on dsDNA
  PMID:19896182;
  PMID:19910535.
• Required continuously for fork progression
  PMID:10834843.
• Mcm467 helicase with leading-strand tracking, polarity opposite to DnaB (3'->5')
  PMID:13679365.
• Mcm2-7 helicase reconstituted; Mcm4 Walker A K574A abolishes it
  PMID:18657510.
• ATP-dependent ssDNA binding
  PMID:17895243.
• CMG subunit PMID:26854665.
• Principal DDK target at firing
  PMID:26854664.
• Required for BIR PMID:20516198.
• CDK-driven nuclear exclusion
  PMID:10559985.

Inferred or not experimentally established here

• Zinc binding rests on the RCA zinc-proteome survey and on the MCM family N-terminal zinc
  motif. In the P30665 sequence I found a C4 cluster at Cys349/Cys352/Cys371/Cys376 (CX2C-X18-CX4C)
  by a simple sequence scan. That is my own observation, not a published structural assignment.
• Premeiotic DNA replication (GO:0006279): the only experimental row cites PMID:20484375, whose
  full text has no meiotic data. I marked it UNDECIDED and flagged it as a possible mis-keyed
  reference.

Key decisions

• 27 protein-binding IPI rows: REMOVE under the GO:0005515 policy. The interactions are real
  but are captured by the complex terms.
• DNA helicase activity / helicase activity rows: MODIFY to GO:0043138 3'-5' DNA helicase
  activity plus GO:0017116, qualified contributes_to. The isolated subunit has no helicase
  activity on its own.
• DNA replication (GO:0006260) and nuclear DNA replication (GO:0033260): MODIFY to the
  specific terms the gene already carries (GO:0006271, GO:1902975).
• Origin binding: KEEP_AS_NON_CORE. ORC recognises the origin; MCM encircles DNA without
  sequence specificity.
• MCM core complex (Mcm467), four-way junction helicase and cytoplasm: KEEP_AS_NON_CORE. These
  are in vitro or regulatory-state findings.