CDK16 (formerly PCTAIRE1) encodes an atypical cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22) belonging to the PCTAIRE subfamily of the CMGC kinase family. Unlike canonical cell-cycle CDKs, CDK16 functions primarily in differentiated post-mitotic cells, with highest expression in brain, testis, and skeletal muscle. The enzyme is activated by cyclin Y (CCNY) and cyclin Y-like 1 (CCNYL1), and its cyclin association is uniquely regulated by PKA phosphorylation at Ser153. CDK16 phosphorylates multiple validated substrates including PRC1 (Thr481, regulating mitotic spindle formation), WIPI2B (Ser395, negatively regulating neuronal autophagosome biogenesis), Rb (promoting G1/S transition), p53 (Ser315, promoting degradation), and p27Kip1 (Ser10, destabilizing the inhibitor). CDK16 localizes dynamically to the cytoplasm, plasma membrane (via CCNY interaction), nucleus during mitosis, and autophagosomes in neurons. It participates in cell cycle regulation at both G2/M and G1/S transitions, neuronal autophagy downstream of AMPK signaling, canonical and non-canonical Wnt signaling via LRP6 phosphorylation, and vesicular transport including synaptic vesicle exocytosis. CDK16 is essential for spermatogenesis, as male Cdk16 knockout mice are sterile with impaired sperm motility and morphological defects. The protein is located on chromosome X in blue whale, consistent with X-linkage of CDK16 across mammals.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000166 nucleotide binding | IEA GO_REF:0000104 | MARK AS OVER ANNOTATED | Summary: CDK16 is a protein kinase that uses ATP as phosphate donor, so it is technically a nucleotide-binding protein. However, this term is extremely broad and is completely subsumed by the more specific GO:0005524 (ATP binding) and GO:0004693 (cyclin-dependent protein serine/threonine kinase activity) annotations already present. Reason: Redundant with the more specific ATP binding and kinase activity annotations. Adds no biological specificity. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: CDK16 is indeed a protein kinase, phosphorylating substrates such as PRC1, WIPI2B, Rb, p53, and p27Kip1. However, this general term is redundant with the more specific GO:0004693 (cyclin-dependent protein serine/threonine kinase activity) already annotated. Reason: The term is correct but too general. The specific CDK Ser/Thr kinase activity term (GO:0004693) captures the function more precisely and is already present. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: CDK16 catalyzes phosphorylation of serine and threonine residues on protein substrates using ATP, confirmed by in vitro kinase assays and identification of specific phosphosites (PRC1-Thr481, WIPI2B-Ser395, p53-Ser315, p27-Ser10). However, this term is a parent of the more specific GO:0004693 (cyclin-dependent protein serine/threonine kinase activity), which is also annotated. Reason: Correct but redundant with the more specific cyclin-dependent protein serine/threonine kinase activity term (GO:0004693). |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: This is the most specific and accurate molecular function term for CDK16. As an atypical CDK of the PCTAIRE subfamily, CDK16 is activated by cyclin Y (CCNY) and cyclin Y-like 1 (CCNYL1), and catalyzes cyclin-dependent phosphorylation of serine/threonine residues. Its EC number is 2.7.11.22 (cyclin-dependent kinase), consistent with this annotation. Although CDK16 may have some basal kinase activity independent of cyclin binding, its full activation requires cyclin association. Reason: This is the defining core molecular function of CDK16, directly matching its EC classification (2.7.11.22) and experimentally validated cyclin-dependent kinase activity. Supporting Evidence: file:BALMU/A0A8B8WEG2/A0A8B8WEG2-uniprot.txt RecName: Full=cyclin-dependent kinase file:BALMU/A0A8B8WEG2/A0A8B8WEG2-deep-research-falcon.md CDK16 functions as a serine/threonine protein kinase (EC 2.7.11.22) that catalyzes the transfer of phosphate groups from ATP to specific serine and threonine residues on target substrate proteins |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: CDK16 contains the protein kinase ATP-binding site (InterPro IPR017441, PROSITE PS00107) and uses ATP as a phosphate donor for its kinase reactions. ATP binding is an essential prerequisite for kinase activity. Reason: ATP binding is a core mechanistic requirement for CDK16 kinase activity, well-supported by domain analysis and consistent with the protein kinase superfamily membership. Supporting Evidence: file:BALMU/A0A8B8WEG2/A0A8B8WEG2-uniprot.txt KW ATP-binding |
| GO:0005634 nucleus | IEA GO_REF:0000118 | KEEP AS NON CORE | Summary: CDK16 can localize to the nucleus during specific cell cycle phases, particularly during mitosis, where it regulates cell cycle progression through phosphorylation of PRC1 and Rb. Nuclear localization has been observed in breast cancer cells and is functionally linked to cell cycle regulation. This TreeGrafter annotation is consistent with the literature. Reason: Nuclear localization is context-dependent (cell-cycle-phase specific) rather than the primary location where CDK16 carries out its main functions. The cytoplasm and plasma membrane are the predominant locations. Supporting Evidence: file:BALMU/A0A8B8WEG2/A0A8B8WEG2-deep-research-falcon.md During specific phases of the cell cycle, particularly during mitosis, CDK16 can localize to the nucleus where it regulates cell cycle progression |
| GO:0005737 cytoplasm | IEA GO_REF:0000118 | ACCEPT | Summary: CDK16 is predominantly localized to the cytoplasm in most cell types. Immunohistochemical analysis in triple-negative breast cancer tissues shows CDK16 is mainly distributed in the cytoplasm. This is the primary location for CDK16 in most cellular contexts. Reason: Cytoplasmic localization is the predominant and best-characterized location for CDK16, supported by immunohistochemistry and cell fractionation studies. Supporting Evidence: file:BALMU/A0A8B8WEG2/A0A8B8WEG2-deep-research-falcon.md CDK16 is predominantly localized to the cytoplasm in most cell types, including breast cancer cells and neurons |
| GO:0006887 exocytosis | IEA GO_REF:0000118 | KEEP AS NON CORE | Summary: CDK16 has documented roles in vesicular transport processes. The CCNY/CDK16 complex regulates vesicular trafficking, and forward genetic analysis in C. elegans identified cyclin Y as necessary for targeting presynaptic components to the axon. CDK16 regulates synaptic vesicle dynamics and exocytosis in neuronal contexts. This TreeGrafter annotation is biologically plausible for CDK16. Reason: Exocytosis is a legitimate biological process for CDK16, particularly in neurons, but it is a secondary consequence of CDK16's role in vesicular transport and cytoskeletal regulation rather than a core evolved function of the kinase. Supporting Evidence: file:BALMU/A0A8B8WEG2/A0A8B8WEG2-deep-research-falcon.md Forward genetic analysis in C. elegans identified cyclin Y as necessary for targeting presynaptic components to the axon, indicating a role in vesicular trafficking |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000118 | UNDECIDED | Summary: CDK16 has been linked to synaptic vesicle dynamics through its role in presynaptic component targeting and vesicular transport. In neurons, CDK16 colocalizes with WIPI2B at autophagosomes, and cyclin Y is required for targeting presynaptic components to the axon. However, direct localization of CDK16 itself to synaptic vesicles (as opposed to regulatory involvement in synaptic vesicle processes) is less firmly established. Reason: The TreeGrafter annotation is plausible given CDK16's neuronal functions and involvement in vesicular transport, but the deep research literature primarily describes functional regulation of synaptic vesicle processes rather than direct physical localization of CDK16 to synaptic vesicles. Full-text evidence from primary studies would be needed to confirm. |
| GO:0016301 kinase activity | IEA GO_REF:0000104 | MARK AS OVER ANNOTATED | Summary: CDK16 is unambiguously a kinase, but this extremely general term is completely subsumed by more specific annotations already present (GO:0004693 cyclin-dependent protein serine/threonine kinase activity, GO:0004674 protein serine/threonine kinase activity, GO:0004672 protein kinase activity). Reason: This is the broadest kinase term in the hierarchy and is fully redundant with the more specific kinase activity terms present. |
| GO:0016740 transferase activity | IEA GO_REF:0000104 | MARK AS OVER ANNOTATED | Summary: As a kinase, CDK16 is technically a transferase (phosphotransferase), but this is an extremely broad parent term that adds no biological information beyond what is captured by the specific kinase terms. Reason: This is the broadest transferase category and is fully redundant with all of the more specific kinase/CDK activity terms present. |
| GO:0031175 neuron projection development | IEA GO_REF:0000118 | KEEP AS NON CORE | Summary: CDK16 is highly expressed in post-mitotic neurons and has documented roles in neurite outgrowth. Proteomic studies in neuroblastoma cells identified CDK16 as a regulator of ERK phosphorylation and neurite outgrowth, a morphological marker of neuronal differentiation. CDK16 also regulates actin dynamics relevant to dendritic spine morphology and synaptic function. This TreeGrafter annotation is well-supported. Reason: Neuron projection development is a legitimate biological process for CDK16, supported by experimental evidence in neuronal cell types. However, it represents a tissue-specific downstream effect rather than the core evolved function of this widely expressed kinase. Supporting Evidence: file:BALMU/A0A8B8WEG2/A0A8B8WEG2-deep-research-falcon.md Proteomic studies in neuroblastoma cells identified CDK16 as a regulator of extracellular signal-regulated kinase (ERK) phosphorylation and neurite outgrowth, a morphological marker of neuronal differentiation |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000108 | ACCEPT | Summary: CDK16 regulates the cell cycle at multiple checkpoints. It controls the G2/M transition through phosphorylation of PRC1 at Thr481 (regulating mitotic spindle formation) and the G1/S transition through phosphorylation of Rb (regulating E2F target gene expression). CDK16 depletion causes G2/M cell cycle arrest and apoptosis. This annotation was inferred from CDK16's cyclin-dependent kinase activity via GO logical inference (GO_REF:0000108), which is appropriate. Reason: Cell cycle regulation is a well-established and experimentally validated function of CDK16, operating through phosphorylation of multiple cell-cycle regulatory substrates (PRC1, Rb, p53, p27Kip1). Supporting Evidence: file:BALMU/A0A8B8WEG2/A0A8B8WEG2-deep-research-falcon.md CDK16 plays dual roles in cell cycle control, regulating both G2/M and G1/S transitions through distinct mechanisms |
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Download this section (compressed HTML)These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
View prediction review YAML · A0A8B8WEG2-protnlm-predictions-review.yaml · Review status: COMPLETE
ProtNLM2 made no predictions (GO or subcellular location) for Protein kinase domain-containing protein (blue whale). The model returned only a protein name.
Source documents: genes/BALMU/A0A8B8WEG2/A0A8B8WEG2-uniprot.txt · genes/BALMU/A0A8B8WEG2/A0A8B8WEG2-goa.tsv
No GO/EC predictions in the reviewed source.
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