KIF2A — curation notes

Deep research status

• First run (--fallback perplexity-lite) stopped (falcon 600 s default timeout; perplexity-lite
  unavailable). The 2400 s rerun was killed (exit 137); a second rerun SUCCEEDED
  (KIF2A-deep-research-falcon.md). It added Trofimova 2018 (PMID:29980677) and Vysloužil 2025
  (PMID:39930500), both cached and used, and noted cell-line variability of the spindle phenotype
  (largely normal bipolar spindles in RPE1).

Identity

• UniProt O00139, kinesin-like protein KIF2A (HK2); kinesin-13 family (central motor domain), with
  paralogs KIF2B and KIF2C/MCAK. Several isoforms.
• Disease: cortical dysplasia, complex, with other brain malformations 3 (CDCBM3).

Core biochemistry: ATP-dependent microtubule depolymerase

• PMID:15302853
• Purified KIF2A depolymerizes GMPCPP microtubules; TTBK2 phosphorylation inhibits it
  PMID:26323690;
  PMID:26323690.
• Historical motility: mouse KIF2 was reported as a plus-end-directed anterograde axonal motor in a
  gliding assay PMID:7535303.
  This contrasts with the kinesin-13 consensus (depolymerization without motile function). The
  motor/transport annotations are therefore kept but treated as non-core.

• GO has no "microtubule depolymerase" MF term (OLS search for "depolymerase" in GO returned only
  polyester depolymerases; MCAK itself is annotated only with motor activity / MT binding). I
  propose an NTR "ATP-dependent microtubule depolymerase activity".

• Structure: PMID:29980677;
  PMID:29980677.

Mitosis

• Required for bipolar spindle assembly; localizes to centrosomes/spindle poles
  PMID:15302853.
• DDA3/PSRC1 recruits KIF2A to spindle and poles and controls spindle dynamics
  PMID:18411309.
• esiRNA screen: Kif2A crucial for spindle formation PMID:15843429.
• Distinct from KIF2B/MCAK PMID:17538014.

Neurons and migration

• Kif2a-/- mice: overextended collateral branches; decreased MT depolymerization in growth cones
  PMID:12887924.
• TTBK2-EB1/3 removes KIF2A from MT ends to regulate MT dynamics in migrating cells PMID:26323690.

Cilium disassembly (module role)

• PMID:25660017
• PMID:25660017
• TTBK2 restrains KIF2A at the mother centriole during cilium growth
  PMID:39930500.
  KIF2A is therefore a negative regulator of cilium length/maintenance as well as the disassembly enzyme.
• PCS syndrome: constitutively active PLK1-KIF2A pathway impairs ciliogenesis PMID:25660017.
• Localization consistent with mother centriole: GOA has centriole and centriolar subdistal
  appendage IDA (PMID:23213374, 3D-SIM). KIF2A is not named in the cached text (probably supplementary
  data), so I defer to the curator.
• Comparator check for NEW/MODIFY to GO:0061523 cilium disassembly: human GOA annotates AURKA,
  NEDD9 and HDAC6 to GO:0061523 (IMP, PMID:17604723). KIF2A carries it in neither human nor mouse.
  KIF2A passes the participation test more directly than those regulators. It is the enzyme that
  depolymerizes the (axonemal/centriolar) microtubules, so it performs the step. I therefore
  re-point the cilium assembly IBA (MODIFY) to cilium disassembly with PMID:25660017 support.

Curation decisions summary

• ACCEPT: MT binding, ATP binding, ATP hydrolysis, MT depolymerization, spindle/spindle pole/
  centrosome/centriole/subdistal appendage, mitotic spindle assembly/organization, MT cytoskeleton
  organization, cytoplasm/cytosol.
• KEEP_AS_NON_CORE: motor activity, MT-based movement, transport (historical motility),
  dendrite/dendritic transport/GABA-ergic synapse/sperm principal piece (electronic, from mouse),
  cell migration regulation, nucleoplasm (HPA), mitotic sister chromatid segregation (ARBA).
• REMOVE: generic protein binding (PSRC1/DDA3 interaction is real but GO:0005515 is uninformative;
  HT screen hits).
• MARK_AS_OVER_ANNOTATED: membrane (HDA, NK-cell membrane proteome). KIF2A has no TM segment and is
  at most peripherally associated.
• MODIFY: cilium assembly (IBA) -> cilium disassembly.

HPA cilium atlas vs module role

• HPA v25: Basal body (Uncertain); Centrosome (Enhanced); main locations Annulus; Basal body;
  Centrosome; Nucleoli; Nucleoplasm. The HPA-sourced GOA rows (GO_REF:0000052) are centrosome,
  cytosol and nucleoplasm; there is no basal body row, consistent with the Uncertain grade. The HPA
  atlas paper (PMID:41005307) is cached as metadata only.
• Module role (stage 7: "MT depolymerase at basal body"): agrees with Miyamoto et al. 2015 (activity
  at the mother centriole), and the HPA centrosome (E) / basal body (U) calls are compatible with it.
  core_functions includes cilium disassembly. KIF2A is pleiotropic: its best-supported roles are
  mitotic spindle bipolarity and neuronal MT dynamics, and cilium disassembly rests on one primary
  study (abstract-only in cache). The module's assignment is reasonable, but KIF2A is not
  cilium-specific. Its common denominator is ATP-dependent MT depolymerization, used at the spindle
  pole, growth cone and mother centriole.