CDK16 (PCTAIRE-1) is an atypical, cyclin-activated, proline-directed serine/threonine protein kinase of the PCTAIRE branch of the CDK family, highly expressed in brain and testis. It consists of a disordered N-terminal extension, a central kinase domain and a short C-terminal tail. Unlike classical CDKs it is activated by cyclin Y (CCNY) or cyclin Y-like 1 (CCNYL1): cyclin Y phosphorylated at Ser100/Ser326 and bound to a 14-3-3 dimer binds the CDK16 kinase domain and N-terminal extension, raising activity more than 100-fold, while phosphorylation of CDK16 Ser153 (PKA) blocks cyclin binding. Myristoylated cyclin Y recruits CDK16 from the cytoplasm to the inner face of the plasma membrane. CDK16 prefers substrates with Pro at +1 and a basic residue at +4; reported substrates include NSF Ser569, p27/CDKN1B Ser10, PRC1 Thr481 and cyclin Y Ser336. In rodents it modulates regulated exocytosis and early secretory traffic, dendrite and neurite growth, and insulin secretion, and in mouse it is required with CCNYL1 for male fertility (sperm annulus and spermiation). In human cells the cyclin Y/CDK16 complex acts downstream of AMPK to promote autophagy, and it supports proliferation of some cancer cell lines.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the eukaryotic CDK node PTN002373304, for which human CDK16 is itself one of the IBD seeds. CDK16 forms a heterodimeric holoenzyme with cyclin Y (or cyclin Y-like 1), with 14-3-3 bound to phospho-cyclin Y. Reason: Cyclin Y/CCNYL1-bound CDK16 is the active form of the kinase; biochemical activation, cryo-EM structure and in-cell recruitment all support the holoenzyme. Supporting Evidence: PMID:41857027 CDK16 interacts with the cyclin box of CCNY, while 14-3-3 provides additional contacts, including with the activation segment of CDK16. PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IPI PMID:19524571 Cyclin Y, a novel membrane-associated cyclin, interacts with... | ACCEPT | Summary: IPI from Jiang et al. 2009 (cyclin Y as a membrane-associated cyclin). The cached abstract foregrounds PFTK1 (CDK14); the full text is not cached. Reason: The abstract names PFTK1, but the curator read the full text and the CDK16-CCNY complex itself is firmly established by independent biochemical and structural work, so the annotation is accepted rather than second-guessed. Supporting Evidence: PMID:41857027 CDK16 interacts with the cyclin box of CCNY, while 14-3-3 provides additional contacts, including with the activation segment of CDK16. PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping (Ser/Thr kinase active site) to protein kinase activity. Reason: Correct but general. CDK16 has experimentally demonstrated cyclin Y-stimulated Ser/Thr kinase activity, so the specific term GO:0004693, which the gene already carries by IBA, is preferred. Proposed replacements: cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. PMID:22184064 CDK16 isolated from murine testis was unphosphorylated, interacted with CCNY, and exhibited kinase activity. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22184064 Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by ... | MODIFY | Summary: IDA for Ser/Thr kinase activity from PMID:22184064; kinase activity of CDK16 was measured directly and is activated by cyclin Y. Reason: The activity is real but the same papers show that it depends on cyclin Y binding, so the more specific GO:0004693 cyclin-dependent protein serine/threonine kinase activity (already on the gene by IBA) captures it. Proposed replacements: cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. PMID:22184064 CDK16 isolated from murine testis was unphosphorylated, interacted with CCNY, and exhibited kinase activity. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22796189 Analysis of substrate specificity and cyclin Y binding of PC... | MODIFY | Summary: IDA for Ser/Thr kinase activity from PMID:22796189; kinase activity of CDK16 was measured directly and is activated by cyclin Y. Reason: The activity is real but the same papers show that it depends on cyclin Y binding, so the more specific GO:0004693 cyclin-dependent protein serine/threonine kinase activity (already on the gene by IBA) captures it. Proposed replacements: cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. PMID:22184064 CDK16 isolated from murine testis was unphosphorylated, interacted with CCNY, and exhibited kinase activity. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl Compara transfer from mouse Cdk16 of Ser/Thr kinase activity. Reason: Correct but general; refine to GO:0004693 as for the experimental rows. Proposed replacements: cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. PMID:22184064 CDK16 isolated from murine testis was unphosphorylated, interacted with CCNY, and exhibited kinase activity. |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN002373304 (eukaryotic CDK node). Reason: Human CDK16 is a bona fide cyclin-activated proline-directed Ser/Thr kinase (cyclin Y raises activity >100-fold); this is the core molecular function. Supporting Evidence: PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. PMID:22184064 CDK16 isolated from murine testis was unphosphorylated, interacted with CCNY, and exhibited kinase activity. |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC 2.7.11.22 mapping to cyclin-dependent protein serine/threonine kinase activity. Reason: The EC assignment is backed by experimental kinase assays with cyclin Y activation. Supporting Evidence: PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. PMID:22184064 CDK16 isolated from murine testis was unphosphorylated, interacted with CCNY, and exhibited kinase activity. |
| GO:0005515 protein binding | IPI PMID:12154078 Regulation of the CDK-related protein kinase PCTAIRE-1 and i... | MODIFY | Summary: interaction of CDK16 with the 14-3-3 isoform YWHAZ reported in PMID:12154078 (Graeser et al. 2002). Reason: Bare protein binding is uninformative. CDK16 contains a phosphorylation-dependent 14-3-3 docking site (pSer119) shown to bind 14-3-3 in vitro and in cells, and 14-3-3 is also part of the CCNY-14-3-3 activating complex; 14-3-3 protein binding is the informative MF. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:12154078 Phosphorylation of one of these sites, Ser119, generates a 14-3-3 binding site, which is functional in vitro as well as in vivo. PMID:9197417 the eta, theta (also known as tau) and zeta isoforms of 14-3-3 proteins |
| GO:0005515 protein binding | IPI PMID:16091426 PCTAIRE protein kinases interact directly with the COPII com... | REMOVE | Summary: Interaction of CDK16 with SEC23A reported in PMID:16091426 (Palmer et al. 2005). Reason: Generic protein binding is uninformative; removal does not mean the interaction is false. The direct CDK16-SEC23A (COPII) interaction is genuine and supports a role in early secretory traffic, but no GO MF term captures a COPII-subunit binding activity informatively. |
| GO:0005515 protein binding | IPI PMID:22184064 Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by ... | MODIFY | Summary: interaction of CDK16 with CCNYL1 reported in PMID:22184064. Reason: Bare protein binding is uninformative. The CCNYL1 interaction is the defining cyclin-partner interaction of CDK16, independently established in low-throughput biochemical and structural work, so the informative MF is cyclin binding. Proposed replacements: cyclin binding Supporting Evidence: PMID:26305884 CCNYL1 interacted with CDK16 and this interaction mutually increased the stability of these two proteins |
| GO:0005515 protein binding | IPI PMID:22184064 Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by ... | MODIFY | Summary: interaction of CDK16 with CCNY reported in PMID:22184064. Reason: Bare protein binding is uninformative. The CCNY interaction is the defining cyclin-partner interaction of CDK16, independently established in low-throughput biochemical and structural work, so the informative MF is cyclin binding. Proposed replacements: cyclin binding Supporting Evidence: PMID:41857027 CDK16 interacts with the cyclin box of CCNY, while 14-3-3 provides additional contacts, including with the activation segment of CDK16. PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. |
| GO:0005515 protein binding | IPI PMID:22184064 Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by ... | MODIFY | Summary: interaction of CDK16 with CCNY isoform 1 reported in PMID:22184064. Reason: Bare protein binding is uninformative. The CCNY isoform 1 interaction is the defining cyclin-partner interaction of CDK16, independently established in low-throughput biochemical and structural work, so the informative MF is cyclin binding. Proposed replacements: cyclin binding Supporting Evidence: PMID:41857027 CDK16 interacts with the cyclin box of CCNY, while 14-3-3 provides additional contacts, including with the activation segment of CDK16. PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Interaction of CDK16 with ZBTB14 reported in the HuRI yeast two-hybrid map PMID:25416956. Reason: Generic protein binding is uninformative; removal does not mean the interaction is false. Binary screen hit with no functional follow-up. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Interaction of CDK16 with APPBP2 reported in the HuRI yeast two-hybrid map PMID:25416956. Reason: Generic protein binding is uninformative; removal does not mean the interaction is false. Binary screen hit with no functional follow-up. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: High-throughput interaction of CDK16 with the 14-3-3 isoform YWHAE reported in the kinase interaction network PMID:25852190. Reason: Bare protein binding is uninformative. CDK16 contains a phosphorylation-dependent 14-3-3 docking site (pSer119) shown to bind 14-3-3 in vitro and in cells, and 14-3-3 is also part of the CCNY-14-3-3 activating complex; 14-3-3 protein binding is the informative MF. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:12154078 Phosphorylation of one of these sites, Ser119, generates a 14-3-3 binding site, which is functional in vitro as well as in vivo. PMID:9197417 the eta, theta (also known as tau) and zeta isoforms of 14-3-3 proteins |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: High-throughput interaction of CDK16 with the 14-3-3 isoform YWHAZ reported in the kinase interaction network PMID:25852190. Reason: Bare protein binding is uninformative. CDK16 contains a phosphorylation-dependent 14-3-3 docking site (pSer119) shown to bind 14-3-3 in vitro and in cells, and 14-3-3 is also part of the CCNY-14-3-3 activating complex; 14-3-3 protein binding is the informative MF. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:12154078 Phosphorylation of one of these sites, Ser119, generates a 14-3-3 binding site, which is functional in vitro as well as in vivo. PMID:9197417 the eta, theta (also known as tau) and zeta isoforms of 14-3-3 proteins |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: High-throughput interaction of CDK16 with CCNYL1 reported in PMID:25852190. Reason: Bare protein binding is uninformative. The CCNYL1 interaction is the defining cyclin-partner interaction of CDK16, independently established in low-throughput biochemical and structural work, so the informative MF is cyclin binding. Proposed replacements: cyclin binding Supporting Evidence: PMID:26305884 CCNYL1 interacted with CDK16 and this interaction mutually increased the stability of these two proteins |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: High-throughput interaction of CDK16 with CCNYL1 reported in PMID:26496610. Reason: Bare protein binding is uninformative. The CCNYL1 interaction is the defining cyclin-partner interaction of CDK16, independently established in low-throughput biochemical and structural work, so the informative MF is cyclin binding. Proposed replacements: cyclin binding Supporting Evidence: PMID:26305884 CCNYL1 interacted with CDK16 and this interaction mutually increased the stability of these two proteins |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Interaction of CDK16 with CDK17 reported in the BioPlex AP-MS map PMID:28514442. Reason: Generic protein binding is uninformative; removal does not mean the interaction is false. A co-purification of two PCTAIRE kinases most likely reflects shared cyclin Y/CCNYL1 or 14-3-3 partners rather than a direct informative activity. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: High-throughput interaction of CDK16 with the 14-3-3 isoform YWHAE reported in the kinase interaction network PMID:32707033. Reason: Bare protein binding is uninformative. CDK16 contains a phosphorylation-dependent 14-3-3 docking site (pSer119) shown to bind 14-3-3 in vitro and in cells, and 14-3-3 is also part of the CCNY-14-3-3 activating complex; 14-3-3 protein binding is the informative MF. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:12154078 Phosphorylation of one of these sites, Ser119, generates a 14-3-3 binding site, which is functional in vitro as well as in vivo. PMID:9197417 the eta, theta (also known as tau) and zeta isoforms of 14-3-3 proteins |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: High-throughput interaction of CDK16 with CCNYL1 reported in PMID:32707033. Reason: Bare protein binding is uninformative. The CCNYL1 interaction is the defining cyclin-partner interaction of CDK16, independently established in low-throughput biochemical and structural work, so the informative MF is cyclin binding. Proposed replacements: cyclin binding Supporting Evidence: PMID:26305884 CCNYL1 interacted with CDK16 and this interaction mutually increased the stability of these two proteins |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: High-throughput interaction of CDK16 with CCNY reported in PMID:32707033. Reason: Bare protein binding is uninformative. The CCNY interaction is the defining cyclin-partner interaction of CDK16, independently established in low-throughput biochemical and structural work, so the informative MF is cyclin binding. Proposed replacements: cyclin binding Supporting Evidence: PMID:41857027 CDK16 interacts with the cyclin box of CCNY, while 14-3-3 provides additional contacts, including with the activation segment of CDK16. PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction of CDK16 with CDK17 reported in the BioPlex dual-cell-line AP-MS map PMID:33961781. Reason: Generic protein binding is uninformative; removal does not mean the interaction is false. A co-purification of two PCTAIRE kinases most likely reflects shared cyclin or 14-3-3 partners. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: High-throughput interaction of CDK16 with CCNYL1 reported in PMID:33961781. Reason: Bare protein binding is uninformative. The CCNYL1 interaction is the defining cyclin-partner interaction of CDK16, independently established in low-throughput biochemical and structural work, so the informative MF is cyclin binding. Proposed replacements: cyclin binding Supporting Evidence: PMID:26305884 CCNYL1 interacted with CDK16 and this interaction mutually increased the stability of these two proteins |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: High-throughput interaction of CDK16 with CCNY reported in PMID:33961781. Reason: Bare protein binding is uninformative. The CCNY interaction is the defining cyclin-partner interaction of CDK16, independently established in low-throughput biochemical and structural work, so the informative MF is cyclin binding. Proposed replacements: cyclin binding Supporting Evidence: PMID:41857027 CDK16 interacts with the cyclin box of CCNY, while 14-3-3 provides additional contacts, including with the activation segment of CDK16. PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: High-throughput interaction of CDK16 with the 14-3-3 isoform YWHAE reported in OpenCell PMID:35271311. Reason: Bare protein binding is uninformative. CDK16 contains a phosphorylation-dependent 14-3-3 docking site (pSer119) shown to bind 14-3-3 in vitro and in cells, and 14-3-3 is also part of the CCNY-14-3-3 activating complex; 14-3-3 protein binding is the informative MF. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:12154078 Phosphorylation of one of these sites, Ser119, generates a 14-3-3 binding site, which is functional in vitro as well as in vivo. PMID:9197417 the eta, theta (also known as tau) and zeta isoforms of 14-3-3 proteins |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: High-throughput interaction of CDK16 with the 14-3-3 isoform YWHAZ reported in OpenCell PMID:35271311. Reason: Bare protein binding is uninformative. CDK16 contains a phosphorylation-dependent 14-3-3 docking site (pSer119) shown to bind 14-3-3 in vitro and in cells, and 14-3-3 is also part of the CCNY-14-3-3 activating complex; 14-3-3 protein binding is the informative MF. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:12154078 Phosphorylation of one of these sites, Ser119, generates a 14-3-3 binding site, which is functional in vitro as well as in vivo. PMID:9197417 the eta, theta (also known as tau) and zeta isoforms of 14-3-3 proteins |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: High-throughput interaction of CDK16 with the 14-3-3 isoform YWHAE reported in the 14-3-3 interactome PMID:36931259. Reason: Bare protein binding is uninformative. CDK16 contains a phosphorylation-dependent 14-3-3 docking site (pSer119) shown to bind 14-3-3 in vitro and in cells, and 14-3-3 is also part of the CCNY-14-3-3 activating complex; 14-3-3 protein binding is the informative MF. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:12154078 Phosphorylation of one of these sites, Ser119, generates a 14-3-3 binding site, which is functional in vitro as well as in vivo. PMID:9197417 the eta, theta (also known as tau) and zeta isoforms of 14-3-3 proteins |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro mapping (protein kinase domain, ATP-binding signature) to ATP binding. Reason: CDK16 has a canonical kinase domain with the glycine-rich ATP-binding loop and the catalytic Lys; ATP binding is true and is a cofactor-level property of the kinase activity rather than a distinct function. Supporting Evidence: file:human/CDK16/CDK16-uniprot.txt Belongs to the protein kinase superfamily. CMGC Ser/Thr |
| GO:0005634 nucleus | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT IBA for nucleus (is_active_in) from the broad CMGC node PTN000623091, seeded by many CDKs and MAPKs. Reason: There is no CDK16-specific evidence of nuclear activity. Endogenous and tagged CDK16 are cytoplasmic and are recruited to the plasma membrane by cyclin Y; CDK16 inhibition causes its substrate PRC1 to move into the nucleus rather than CDK16 acting there. The nuclear role belongs to other branches of the node (e.g. transcriptional CDKs). Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000623091 SUPPORTS SOURCE BUT NOT TARGET Broad CMGC ancestor whose nuclear IBD is grounded in transcriptional/cell-cycle CDKs and MAPKs; the PCTAIRE branch, including CDK16, has only cytoplasmic and plasma-membrane localisation evidence. Supporting Evidence: PMID:10511311 Indirect immunofluorescence indicated that PCTAIRE-1 exhibits cytoplasmic distribution throughout the cell cycle. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for cytoplasm from PTN002373304; CDK16 is one of the IBD seeds. Reason: CDK16 is cytoplasmic in multiple cell types. Supporting Evidence: PMID:10511311 Indirect immunofluorescence indicated that PCTAIRE-1 exhibits cytoplasmic distribution throughout the cell cycle. PMID:22798068 In MIN6 cells, BRSK2 co-localizes with PCTAIRE1 in the cytoplasm |
| GO:0005737 cytoplasm | IDA PMID:22798068 Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1... | ACCEPT | Summary: IDA: PCTAIRE1 co-localises with BRSK2 in the cytoplasm of MIN6 cells. Reason: Consistent with all localisation data for CDK16. Supporting Evidence: PMID:10511311 Indirect immunofluorescence indicated that PCTAIRE-1 exhibits cytoplasmic distribution throughout the cell cycle. PMID:22798068 In MIN6 cells, BRSK2 co-localizes with PCTAIRE1 in the cytoplasm |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA for cytoplasm. Reason: Consistent with experimental localisation. Supporting Evidence: PMID:10511311 Indirect immunofluorescence indicated that PCTAIRE-1 exhibits cytoplasmic distribution throughout the cell cycle. PMID:22798068 In MIN6 cells, BRSK2 co-localizes with PCTAIRE1 in the cytoplasm |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence (cytosol). Reason: Soluble cytoplasmic kinase; cytosol is consistent with the IF data. Supporting Evidence: PMID:10511311 Indirect immunofluorescence indicated that PCTAIRE-1 exhibits cytoplasmic distribution throughout the cell cycle. |
| GO:0005886 plasma membrane | EXP PMID:22184064 Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by ... | ACCEPT | Summary: EXP: CCNY-dependent recruitment of CDK16 to the plasma membrane in human cells. Reason: Membrane recruitment by myristoylated cyclin Y is a defining, phosphorylation-regulated property of CDK16. Supporting Evidence: PMID:22184064 a fraction of CDK16-GFP was recruited to the plasma membrane PMID:22184064 Thus, CDK16 is a membrane-targeted CDK essential for spermatogenesis. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence (plasma membrane). Reason: Consistent with CCNY-dependent membrane targeting. Supporting Evidence: PMID:22184064 a fraction of CDK16-GFP was recruited to the plasma membrane PMID:22184064 Thus, CDK16 is a membrane-targeted CDK essential for spermatogenesis. |
| GO:0005886 plasma membrane | IDA PMID:19524571 Cyclin Y, a novel membrane-associated cyclin, interacts with... | ACCEPT | Summary: IDA from Jiang et al. 2009 (cyclin Y paper; abstract foregrounds PFTK1/CDK14). Reason: Deferring to the curator, who read the full text; plasma membrane localisation of CDK16 via cyclin Y is independently established. Supporting Evidence: PMID:22184064 a fraction of CDK16-GFP was recruited to the plasma membrane PMID:22184064 Thus, CDK16 is a membrane-targeted CDK essential for spermatogenesis. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA for plasma membrane. Reason: Consistent with experimental data. Supporting Evidence: PMID:22184064 a fraction of CDK16-GFP was recruited to the plasma membrane PMID:22184064 Thus, CDK16 is a membrane-targeted CDK essential for spermatogenesis. |
| GO:0006468 protein phosphorylation | TAS PMID:1437147 PCTAIRE-1 and PCTAIRE-3, two members of a novel cdc2/CDC28-r... | ACCEPT | Summary: TAS from the original cloning paper describing PCTAIRE-1 as a putative Ser/Thr kinase. Reason: Protein phosphorylation is the process directly executed by the kinase; later work confirmed activity and substrates (p27 Ser10, NSF Ser569, PRC1 Thr481). Supporting Evidence: PMID:1437147 encode putative serine/threonine-specific protein kinases PMID:25205104 In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. |
| GO:0006887 exocytosis | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA for exocytosis from the vertebrate PCTAIRE node PTN004656776. Reason: The underlying rodent evidence is regulatory: Pctaire1 phosphorylates NSF Ser569 and restrains NSF oligomerisation, and kinase-dead Pctaire1 increases stimulated reporter release. CDK16 does not execute membrane fusion; it modulates it. The PAINT node PTN004656776 (Euteleostomi) is seeded only by mouse Cdk16, so placement is not in question, but the term should be the regulation term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN004656776 SUPPORTS TRANSFER Euteleostomi PCTAIRE node seeded by mouse Cdk16 (MGI:97516); human CDK16 is inside the clade, but the seed evidence shows a regulatory kinase role, so the transferred term should be the regulation term. Proposed replacements: regulation of exocytosis Supporting Evidence: PMID:16461345 binds directly to and is phosphorylated by Pctaire1 on serine 569 PMID:16461345 expression of either Pctaire1-KD or NSF-S569A in PC12 cells significantly increases high K(+)-stimulated growth hormone release |
| GO:0006887 exocytosis | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl Compara transfer of exocytosis from mouse Cdk16. Reason: The underlying rodent evidence is regulatory: Pctaire1 phosphorylates NSF Ser569 and restrains NSF oligomerisation, and kinase-dead Pctaire1 increases stimulated reporter release. CDK16 does not execute membrane fusion; it modulates it. The PAINT node PTN004656776 (Euteleostomi) is seeded only by mouse Cdk16, so placement is not in question, but the term should be the regulation term. Proposed replacements: regulation of exocytosis Supporting Evidence: PMID:16461345 binds directly to and is phosphorylated by Pctaire1 on serine 569 PMID:16461345 expression of either Pctaire1-KD or NSF-S569A in PC12 cells significantly increases high K(+)-stimulated growth hormone release |
| GO:0006887 exocytosis | ISS GO_REF:0000024 | MODIFY | Summary: ISS from mouse Cdk16 (Q04735) for exocytosis. Reason: The underlying rodent evidence is regulatory: Pctaire1 phosphorylates NSF Ser569 and restrains NSF oligomerisation, and kinase-dead Pctaire1 increases stimulated reporter release. CDK16 does not execute membrane fusion; it modulates it. The PAINT node PTN004656776 (Euteleostomi) is seeded only by mouse Cdk16, so placement is not in question, but the term should be the regulation term. Proposed replacements: regulation of exocytosis Supporting Evidence: PMID:16461345 binds directly to and is phosphorylated by Pctaire1 on serine 569 PMID:16461345 expression of either Pctaire1-KD or NSF-S569A in PC12 cells significantly increases high K(+)-stimulated growth hormone release |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of spermatogenesis from mouse Cdk16. Reason: Mouse Cdk16 knockout males are infertile with sperm annulus, head and residual-cytoplasm defects, and CDK16 acts within spermatids with its partner CCNYL1. This is established in mouse only, and the specific step CDK16 phosphorylates is unknown, so it is kept as a non-core developmental role transferred by orthology. Supporting Evidence: PMID:22184064 Thus, CDK16 is a membrane-targeted CDK essential for spermatogenesis. PMID:26305884 CCNYL1 interacted with CDK16 and this interaction mutually increased the stability of these two proteins |
| GO:0007283 spermatogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Cdk16 for spermatogenesis. Reason: Mouse Cdk16 knockout males are infertile with sperm annulus, head and residual-cytoplasm defects, and CDK16 acts within spermatids with its partner CCNYL1. This is established in mouse only, and the specific step CDK16 phosphorylates is unknown, so it is kept as a non-core developmental role transferred by orthology. Supporting Evidence: PMID:22184064 Thus, CDK16 is a membrane-targeted CDK essential for spermatogenesis. PMID:26305884 CCNYL1 interacted with CDK16 and this interaction mutually increased the stability of these two proteins |
| GO:0007283 spermatogenesis | NAS PMID:19524571 Cyclin Y, a novel membrane-associated cyclin, interacts with... | KEEP AS NON CORE | Summary: NAS citing the cyclin Y paper (PMID:19524571). Reason: Mouse Cdk16 knockout males are infertile with sperm annulus, head and residual-cytoplasm defects, and CDK16 acts within spermatids with its partner CCNYL1. This is established in mouse only, and the specific step CDK16 phosphorylates is unknown, so it is kept as a non-core developmental role transferred by orthology. Supporting Evidence: PMID:22184064 Thus, CDK16 is a membrane-targeted CDK essential for spermatogenesis. PMID:26305884 CCNYL1 interacted with CDK16 and this interaction mutually increased the stability of these two proteins |
| GO:0008021 synaptic vesicle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA (colocalizes_with) from PTN004656776. Reason: Rat brain co-immunoprecipitation places Pctaire1 with NSF and synaptic vesicle proteins; colocalizes_with is an appropriately weak claim, but synaptic vesicles are not where the core activity is defined. Supporting Evidence: PMID:16461345 Pctaire1 associates with NSF and synaptic vesicle-associated proteins in adult rat brain |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer (colocalizes_with synaptic vesicle). Reason: Rat brain co-immunoprecipitation places Pctaire1 with NSF and synaptic vesicle proteins; colocalizes_with is an appropriately weak claim, but synaptic vesicles are not where the core activity is defined. Supporting Evidence: PMID:16461345 Pctaire1 associates with NSF and synaptic vesicle-associated proteins in adult rat brain |
| GO:0008021 synaptic vesicle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Cdk16 (colocalizes_with synaptic vesicle). Reason: Rat brain co-immunoprecipitation places Pctaire1 with NSF and synaptic vesicle proteins; colocalizes_with is an appropriately weak claim, but synaptic vesicles are not where the core activity is defined. Supporting Evidence: PMID:16461345 Pctaire1 associates with NSF and synaptic vesicle-associated proteins in adult rat brain |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:22184064 Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by ... | ACCEPT | Summary: IDA: CCNY-dependent recruitment to the inner face of the plasma membrane. Reason: CDK16 is a peripheral membrane protein brought to the cytoplasmic face of the plasma membrane by myristoylated cyclin Y. Supporting Evidence: PMID:22184064 a fraction of CDK16-GFP was recruited to the plasma membrane PMID:22184064 Thus, CDK16 is a membrane-targeted CDK essential for spermatogenesis. |
| GO:0010508 positive regulation of autophagy | IDA PMID:32098961 AMPK-dependent activation of the Cyclin Y/CDK16 complex cont... | KEEP AS NON CORE | Summary: IDA: Cyclin Y/CDK16 overexpression promotes autophagy and is required for efficient AMPK-induced autophagy in human cells. Reason: Regulation is the right relation: AMPK phosphorylates cyclin Y S326 to activate CDK16, and the complex promotes autophagy. The relevant CDK16 substrate in this pathway is not fully defined (WIPI2B S395 has been proposed in neurons), so this is kept as a supported but non-core regulatory role. Supporting Evidence: PMID:32098961 When expressed in cells, Cyclin Y/CDK16 is sufficient to promote autophagy. PMID:42774886 purified mammalian PP2A and CDK16 directly modified WIPI2B S395 phosphorylation in vitro |
| GO:0030133 transport vesicle | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt SubCell mapping (secretory vesicle, by similarity to rat). Reason: Vesicle association is supported in rodent brain and is consistent with the trafficking roles, but is not experimentally shown for the human protein. Supporting Evidence: PMID:16461345 Pctaire1 associates with NSF and synaptic vesicle-associated proteins in adult rat brain |
| GO:0030252 growth hormone secretion | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl Compara transfer of growth hormone secretion from mouse Cdk16. Reason: The growth hormone release measured in PC12 cells is a transfected reporter of Ca2+-regulated exocytosis, not physiological GH secretion by somatotrophs, and kinase-dead Pctaire1 increased it. The evidence therefore supports regulation of exocytosis, not involvement in growth hormone secretion. Proposed replacements: regulation of exocytosis Supporting Evidence: PMID:16461345 binds directly to and is phosphorylated by Pctaire1 on serine 569 PMID:16461345 expression of either Pctaire1-KD or NSF-S569A in PC12 cells significantly increases high K(+)-stimulated growth hormone release |
| GO:0030252 growth hormone secretion | ISS GO_REF:0000024 | MODIFY | Summary: ISS from mouse Cdk16 for growth hormone secretion. Reason: The growth hormone release measured in PC12 cells is a transfected reporter of Ca2+-regulated exocytosis, not physiological GH secretion by somatotrophs, and kinase-dead Pctaire1 increased it. The evidence therefore supports regulation of exocytosis, not involvement in growth hormone secretion. Proposed replacements: regulation of exocytosis Supporting Evidence: PMID:16461345 binds directly to and is phosphorylated by Pctaire1 on serine 569 PMID:16461345 expression of either Pctaire1-KD or NSF-S569A in PC12 cells significantly increases high K(+)-stimulated growth hormone release |
| GO:0031175 neuron projection development | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA for neuron projection development from PTN004656776. Reason: Rodent knockdown and overexpression show that Pctaire1 kinase signalling (downstream of Cdk5 phosphorylation at Ser95) controls neurite and dendrite growth, with different forms promoting or inhibiting outgrowth. That is evidence of a regulatory kinase, not of a component that executes projection development, so the regulation term is preferred. Node placement at PTN004656776 (seeded by mouse Cdk16) is not disputed. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN004656776 SUPPORTS TRANSFER Euteleostomi PCTAIRE node seeded by mouse Cdk16 (MGI:97516); human CDK16 is inside the clade, but the seed evidence shows a regulatory kinase role, so the transferred term should be the regulation term. Proposed replacements: regulation of neuron projection development Supporting Evidence: PMID:21335063 Knockdown of Pctaire1 abolishes dendrite development PMID:12154078 various forms of PCTAIRE-1 transfected into neuroblastoma cell lines could either promote or inhibit neurite outgrowth |
| GO:0031175 neuron projection development | IEA GO_REF:0000107 | MODIFY | Summary: Ensembl Compara transfer of neuron projection development from mouse Cdk16. Reason: Rodent knockdown and overexpression show that Pctaire1 kinase signalling (downstream of Cdk5 phosphorylation at Ser95) controls neurite and dendrite growth, with different forms promoting or inhibiting outgrowth. That is evidence of a regulatory kinase, not of a component that executes projection development, so the regulation term is preferred. Node placement at PTN004656776 (seeded by mouse Cdk16) is not disputed. Proposed replacements: regulation of neuron projection development Supporting Evidence: PMID:21335063 Knockdown of Pctaire1 abolishes dendrite development PMID:12154078 various forms of PCTAIRE-1 transfected into neuroblastoma cell lines could either promote or inhibit neurite outgrowth |
| GO:0031175 neuron projection development | ISS GO_REF:0000024 | MODIFY | Summary: ISS from mouse Cdk16 for neuron projection development. Reason: Rodent knockdown and overexpression show that Pctaire1 kinase signalling (downstream of Cdk5 phosphorylation at Ser95) controls neurite and dendrite growth, with different forms promoting or inhibiting outgrowth. That is evidence of a regulatory kinase, not of a component that executes projection development, so the regulation term is preferred. Node placement at PTN004656776 (seeded by mouse Cdk16) is not disputed. Proposed replacements: regulation of neuron projection development Supporting Evidence: PMID:21335063 Knockdown of Pctaire1 abolishes dendrite development PMID:12154078 various forms of PCTAIRE-1 transfected into neuroblastoma cell lines could either promote or inhibit neurite outgrowth |
| GO:0045202 synapse | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt SubCell mapping (synaptosome, by similarity to rat). Reason: Pctaire1 is found as dendritic puncta with synaptic markers and with synaptic vesicle proteins in rodent brain; plausible but not shown for human. Supporting Evidence: PMID:21335063 Pctiare1 is expressed as puncta and co-localized with synaptic marker in dendrites |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Inter-ontology inference from GO:0004693 to regulation of cell cycle. Reason: This is a mechanical inference from the CDK MF term. CDK16 knockout mice develop normally, and the evidence for a cell-cycle role (p27 Ser10 and PRC1 Thr481 phosphorylation, mitotic defects on knockdown) is restricted to transformed cells. Kept as non-core. Supporting Evidence: PMID:25205104 PCTAIRE1 was not similarly involved in proliferation of nontransformed cells PMID:30992425 we identified PRC1 as the first substrate of the CDK16/CCNY complex |
| GO:0061178 regulation of insulin secretion involved in cellular response to glucose stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer from mouse. Reason: Overexpression of active PCTAIRE1 in MIN6 Ξ²-cells inhibited glucose-stimulated insulin secretion in a kinase-dependent manner downstream of BRSK2. Regulation is the right relation, but the evidence is from a mouse cell line with overexpression, so it is non-core. Supporting Evidence: PMID:22798068 Importantly, this function of PCTAIRE1 depends on its kinase activity. PMID:22798068 Upon activation, BRSK2 interacted with and phosphorylated PCTAIRE1 on its Ser-12 residue, leading to inhibition of insulin secretion in MIN6 cells. |
| GO:0061178 regulation of insulin secretion involved in cellular response to glucose stimulus | IMP PMID:22798068 Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1... | KEEP AS NON CORE | Summary: IMP in MIN6 Ξ²-cells (BRSK2-PCTAIRE1 axis). Reason: Overexpression of active PCTAIRE1 in MIN6 Ξ²-cells inhibited glucose-stimulated insulin secretion in a kinase-dependent manner downstream of BRSK2. Regulation is the right relation, but the evidence is from a mouse cell line with overexpression, so it is non-core. Supporting Evidence: PMID:22798068 Importantly, this function of PCTAIRE1 depends on its kinase activity. PMID:22798068 Upon activation, BRSK2 interacted with and phosphorylated PCTAIRE1 on its Ser-12 residue, leading to inhibition of insulin secretion in MIN6 cells. |
| GO:0106310 protein serine kinase activity | EXP PMID:22184064 Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by ... | ACCEPT | Summary: EXP for protein serine kinase activity from PMID:22184064. Reason: CDK16 phosphorylates serine residues on peptide and protein substrates (PCTAIRE-tide, NSF Ser569, p27 Ser10, CCNY Ser336). The term is accurate; it is a reaction-level description complementary to GO:0004693, which is not its descendant. Supporting Evidence: PMID:16461345 binds directly to and is phosphorylated by Pctaire1 on serine 569 PMID:25205104 In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. |
| GO:0106310 protein serine kinase activity | EXP PMID:22796189 Analysis of substrate specificity and cyclin Y binding of PC... | ACCEPT | Summary: EXP for protein serine kinase activity from PMID:22796189. Reason: CDK16 phosphorylates serine residues on peptide and protein substrates (PCTAIRE-tide, NSF Ser569, p27 Ser10, CCNY Ser336). The term is accurate; it is a reaction-level description complementary to GO:0004693, which is not its descendant. Supporting Evidence: PMID:16461345 binds directly to and is phosphorylated by Pctaire1 on serine 569 PMID:25205104 In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. |
| GO:0106310 protein serine kinase activity | EXP PMID:22798068 Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1... | ACCEPT | Summary: EXP for protein serine kinase activity from PMID:22798068. Reason: CDK16 phosphorylates serine residues on peptide and protein substrates (PCTAIRE-tide, NSF Ser569, p27 Ser10, CCNY Ser336). The term is accurate; it is a reaction-level description complementary to GO:0004693, which is not its descendant. Supporting Evidence: PMID:16461345 binds directly to and is phosphorylated by Pctaire1 on serine 569 PMID:25205104 In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea mapping (RHEA:17989, L-seryl-[protein] phosphorylation). Reason: CDK16 phosphorylates serine residues on peptide and protein substrates (PCTAIRE-tide, NSF Ser569, p27 Ser10, CCNY Ser336). The term is accurate; it is a reaction-level description complementary to GO:0004693, which is not its descendant. Supporting Evidence: PMID:16461345 binds directly to and is phosphorylated by Pctaire1 on serine 569 PMID:25205104 In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PMID:22796189 Here we demonstrate that binding of PCTAIRE-1 to cyclin Y increases (> 100-fold) PCTAIRE-1 activity towards PCTAIRE-tide. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Which CDK16 substrate mediates its effect on autophagy in non-neuronal human cells, and is WIPI2B S395 phosphorylation conserved outside neurons?
Q: Should rodent-derived process annotations (exocytosis, neuron projection development, growth hormone secretion) be represented as regulation terms across the PCTAIRE PAINT node PTN004656776?
Q: Does CDK16 have any nuclear activity that would justify the CMGC-wide nucleus IBA, or is its nuclear absence a PCTAIRE-branch property?
Experiment: Phosphoproteomics in CCNYL1/CDK16 knockout mouse spermatids, using analog-sensitive CDK16, to identify the substrates that act at the sperm annulus.
Hypothesis: CDK16-CCNYL1 phosphorylates septin-ring or annulus-associated proteins required for annulus positioning and spermiation.
Type: chemical-genetic phosphoproteomics
Experiment: Test whether endogenous human CDK16 phosphorylates NSF Ser569 in neurons or Ξ²-cells, and whether NSF S569A rescues the exocytosis phenotype of CDK16 loss.
Hypothesis: NSF Ser569 phosphorylation is the mechanism by which CDK16 restrains regulated exocytosis in human cells.
Type: phosphosite-specific rescue and secretion assay
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)