cdc2 (Cdk1, p34cdc2) — S. pombe — review notes

UniProt: P04551 (CDK1_SCHPO). PomBase SPBC11B10.09. EC 2.7.11.22.

Core identity

Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1), the master regulator of the
fission-yeast mitotic and meiotic cell cycle (Nurse, Nobel Prize 2001). It drives both the G1/S and G2/M
transitions. It is catalytically inert as a monomer and is activated by binding a B-type cyclin (mitotic
cyclin Cdc13; G1/S cyclins Cig1/Cig2/Puc1), CAK-mediated activating phosphorylation of Thr167, and removal
of inhibitory Tyr15 phosphorylation by Cdc25; it is inhibited by Wee1/Mik1 phosphorylation of Tyr15 and by
the CDK inhibitor Rum1 in G1.

Key supporting evidence (verbatim)

• Founding genetic identification of dual G1/G2 roles: PMID:7254352
• Tyr15 phospho-regulation of mitotic entry: PMID:2682257
• Thr167 activating phosphorylation / cyclin association: PMID:1655416
• Master regulator + ORC2/Orp2 substrate, anti-rereplication: PMID:11486016
• suc1/Cks1 is a component of the holoenzyme: PMID:3322810
• Meiosis: PMID:7498766
• Single CDK can run the whole cell cycle; activity thresholds order substrate phosphorylation: PMID:27984725 and PMID:27984725. >200 substrates identified.
• Substrate dis1 (chromosome segregation): PMID:16920624
• G1 inhibition by pheromone via G1 cyclin B-CDK: PMID:9034336

Annotation review strategy

• MF kinase terms (GO:0004693 cyclin-dependent protein serine/threonine kinase activity; GO:0097472 CDK activity;
  GO:0004674 protein serine/threonine kinase activity; GO:0004672 protein kinase activity; GO:0106310 protein
  serine kinase activity) — all describe the CORE catalytic activity. GO:0004693 is the most informative; ACCEPT
  it as core. The many duplicate GO:0004693 / GO:0004674 entries (esp. ~70 from PMID:27984725, which are
  individual substrate-phosphorylation observations) are all valid IDA/EXP support for the same core MF; ACCEPT
  (one representative is the core; the rest are redundant duplicates of the same MF, also ACCEPT). GO:0004672 and
  GO:0004674 are less specific parents → MODIFY/ACCEPT-as-supporting; GO:0106310 protein serine kinase activity is
  a partial/over-narrow Rhea/ISS import (CDK is Ser/Thr) → KEEP_AS_NON_CORE/ACCEPT but not core.
• BP core: G1/S transition (GO:0000082), G2/M transition (GO:0000086), positive regulation of G1/S (GO:1900087),
  premeiotic DNA replication initiation (GO:1904514), positive regulation of meiotic cell cycle (GO:0051446) —
  ACCEPT as core cell-cycle driving functions.
• Numerous specific downstream/substrate-process BP terms (kinetochore assembly, sister chromatid biorientation,
  spindle elongation, chromosome condensation, contractile ring/cytokinesis inhibition, septum biogenesis, NHEJ
  restraint, telomere tethering, APC regulation, protein catabolism, mitotic exit, etc.) are genuine experimentally
  supported phosphorylation-substrate roles but are peripheral consequences of the single master kinase acting on
  many substrates → KEEP_AS_NON_CORE (real but not the core function). Mark clearly over-reaching/very narrow ones
  appropriately.
• CC: cyclin-dependent protein kinase holoenzyme complex (GO:0000307) is core. nucleus/cytoplasm/SPB/spindle/
  kinetochore/chromatin localizations are valid IDA active-site locations → ACCEPT/KEEP_AS_NON_CORE. IEA nucleus
  (ARBA) and IEA cytoplasm duplicate the experimental CC; ACCEPT/redundant.
• protein binding (GO:0005515, bare) — uninformative; MARK_AS_OVER_ANNOTATED, partners (orc2, pch1, rum1, cig2,
  cdc13, suc1, wos2) better captured by holoenzyme complex and specific BP terms.
• NOT nuclear pore complex assembly (GO:0051292, negated, PMID:35354597) — ACCEPT the negation.
• IEA GO:0004693 from EC/ARBA and InterPro GO:0004672 — redundant electronic versions of experimentally proven
  activity; ACCEPT (correct) but redundant.