CDK16 (PCTAIRE-1, PCTK1) — human, UniProt Q00536
Session log
2026-10-21 — initial review
just fetch-gene human CDK16 created the UniProt, GOA (65 rows) and stub files.
just deep-research human CDK16 --provider falcon FAILED: the Edison/falcon client
exited with Exception: Failed to authenticate ("All providers failed"). No
deep-research file was produced; this review is built from the cached publications
listed below, the UniProt record and PANTHER/PAINT data.
just fetch-gene-pmids human CDK16 cached all 16 GOA-cited PMIDs. A further set of
CDK16 papers was already cached in publications/ and was read here.
- Context: this review is the experimentally characterised comparator for the blue/minke
whale CDK16 model genes/BALMU/A0A8B8WEG2, which is placed in the same PANTHER
subfamily (PTHR24056:SF174, CYCLIN-DEPENDENT KINASE 16).
What is experimentally established, and in which species
Human protein (direct evidence)
- Ser/Thr protein kinase activity of recombinant and endogenous human PCTAIRE-1; optimal
motif needs Pro at +1 and a basic residue at +4; cyclin Y binding increases activity
100-fold PMID:22796189.
- Cyclin Y recruits CDK16 to the plasma membrane in human cells; S153 phosphorylation
(PKA site) blocks CCNY binding PMID:22184064.
- Activation requires cyclin Y phosphorylated at S100/S326 bound to 14-3-3
PMID:26205494; the cryo-EM structure shows
CDK16 contacting the CCNY cyclin box and 14-3-3 PMID:41857027.
- Crystal structures of the isolated kinase domain with inhibitors PMID:28057719.
- Substrates in human cells: p27 Ser10 PMID:25205104, PRC1 Thr481 PMID:30992425, CCNY Ser336 PMID:26205494.
- AMPK phosphorylates CCNY S326 to promote CCNY-CDK16 activation; CCNY/CDK16 is
sufficient to promote autophagy in cells PMID:32098961.
- Cytoplasmic localisation PMID:10511311.
- Direct interaction with the COPII subunit SEC23A; depletion or kinase-dead expression
impairs ER-to-Golgi cargo transport PMID:16091426.
- Proliferation/mitosis role is cancer-cell specific PMID:25205104.
- Candidate X-linked intellectual disability gene, not confirmed PMID:25644381; patient variants are
inactive and cannot bind CCNY PMID:26205494.
Mouse / rat (ortholog evidence; source of the ISS/IEA/IBA rows)
- Cdk16 knockout male mice are infertile with sperm annulus, head and residual-cytoplasm
defects; development otherwise normal PMID:22184064.
- CCNYL1 (not CCNY) is the partner required in testis; mutual stabilisation
PMID:26305884.
- Pctaire1 phosphorylates NSF Ser569 and restrains NSF oligomerisation; kinase-dead
Pctaire1 increases stimulated growth hormone (reporter) release from PC12 cells
PMID:16461345. The "growth hormone secretion" and "exocytosis" annotations derive
from this regulatory, reporter-based evidence.
- Cdk5/p35 phosphorylates Pctaire1 Ser95 and activates it PMID:12084709; knockdown in
hippocampal neurons abolishes dendrite development PMID:21335063. Neurite phenotypes
in Neuro-2A PMID:12154078; MRTF/Srf regulates Pctaire1 expression in brain
development PMID:20534669.
- Brain substrates from a chemical-genetic screen: AAK1, dynamin 1, synaptojanin 1
PMID:30880224 (abstract only).
- In MIN6 β-cells, BRSK2 phosphorylates PCTAIRE1 Ser12; overexpressed active PCTAIRE1
inhibits glucose-stimulated insulin secretion in a kinase-dependent manner
PMID:22798068.
- Mouse neurons / C. elegans: CDK16 phosphorylates WIPI2B S395, antagonised by PP2A, in
neuronal autophagosome biogenesis PMID:42774886 (2026; not yet in GOA).
Phylogenetic grounding
- PANTHER PTHR24056:SF174 (CYCLIN-DEPENDENT KINASE 16).
- PAINT PTN002373304 (taxon Eukaryota, a broad CDK node) carries GO:0004693, GO:0000307
and GO:0005737; CDK16 (Q00536) is itself one of the IBD seeds for GO:0000307 and
GO:0005737.
- PAINT PTN004656776 (taxon Euteleostomi, the vertebrate PCTAIRE node) carries GO:0006887
exocytosis, GO:0031175 neuron projection development and GO:0008021 synaptic vesicle;
it is seeded only by mouse Cdk16 (MGI:97516), i.e. the rodent NSF/neurite work.
- PAINT PTN000623091 (broad CMGC node) gives GO:0005634 nucleus; there is no CDK16-
specific evidence for nuclear activity and the endogenous protein is cytoplasmic.
Curation decisions in brief
- Kinase MF terms: the specific supported term is GO:0004693 (cyclin-dependent protein
serine/threonine kinase activity); general kinase terms are refined to it.
- Process terms from rodent overexpression/reporter assays are recast as regulation
(regulation of exocytosis; regulation of neuron projection development) rather than
participation.
- Protein-binding rows: CCNY/CCNYL1 → cyclin binding; 14-3-3 → 14-3-3 protein binding;
others removed as uninformative.
- No NEW terms were added. WIPI2B / autophagosome biogenesis evidence is recent, partly
worm-based, and recorded here and as a suggested question.