CDKN1B encodes p27Kip1 (p27), a 198-residue, largely intrinsically disordered member of the Cip/Kip family of cyclin-dependent kinase regulators (with p21/CDKN1A and p57/CDKN1C). It is not an enzyme: it acts stoichiometrically, through a bipartite N-terminal kinase-inhibitory (CDI) domain spanning roughly residues 25-93, whose subdomain 1 docks into the MRAIL groove of the cyclin box and whose subdomain 2 then folds onto the CDK, rearranging its N-terminal lobe and inserting a 3(10) helix into the catalytic cleft as an ATP mimic. The principal consequence is potent inhibition of cyclin E-CDK2 and cyclin A-CDK2 in the nucleus, which keeps retinoblastoma-family proteins hypophosphorylated, holds E2F-dependent transcription in check, and restrains the G1/S transition; p27 is the CKI through which antimitogenic inputs such as TGF-beta signalling and cell-cell contact impose quiescence, and it is maximal in quiescent cells and early G1. Toward cyclin D-CDK4/6 its role is different and context-dependent: p27 promotes assembly of the ternary complex, escorts it to the nucleus, and depending on abundance and tyrosine phosphorylation may inhibit or permit CDK4 activity, so the protein is better described as a CDK regulator with a dominant inhibitory mode than as a universal inhibitor. Its activity is set largely post-translationally: phosphorylation of Thr187 by cyclin-CDK2 creates the phosphodegron read by CKS1 and the SCF(SKP2) ubiquitin ligase, giving the switch-like positive feedback that destroys p27 at G1/S, while Ser10 phosphorylation (by UHMK1/KIS) drives CRM1/Ran-dependent nuclear export, Thr157/Thr198 phosphorylation by AKT and RSK promotes 14-3-3 binding and cytoplasmic retention, Tyr74/Tyr88 phosphorylation by Src-family and ABL kinases relieves CDK inhibition, and cytoplasmic p27 is also ubiquitinated by the KPC (RNF123-UBAC1) complex. The cytoplasmic pool has functions independent of CDK inhibition, binding RhoA to dampen RhoA-ROCK signalling and binding the microtubule-destabilising protein stathmin, thereby influencing actin and microtubule dynamics, cell migration and invasion. p27 is a haploinsufficient tumour suppressor: its protein levels are reduced, largely by enhanced proteasomal degradation, in many epithelial cancers, and germline loss-of-function variants cause multiple endocrine neoplasia type 4 (MEN4).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity | IDA PMID:8033212 Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and ... | ACCEPT | Summary: p27 regulates the activity of cyclin-dependent kinases: it binds cyclin E-CDK2 and cyclin A-CDK2 and blocks their activation, and also modulates cyclin D-CDK4. Reason: Core function, established in the cloning paper by direct kinase assays: p27 prevents activation of cyclin E-CDK2 and inhibits already-active complexes, and blocks Rb phosphorylation by cyclin E-CDK2, cyclin A-CDK2 and cyclin D2-CDK4. The parent 'regulation' term (rather than the negative-regulation child) is appropriate for this gene, because p27 is not a uniform inhibitor: at substoichiometric levels and when phosphorylated on Tyr74/Tyr88 it promotes assembly and can permit cyclin D-CDK4 activity. Supporting Evidence: PMID:8033212 p27Kip1 associates with cyclin E-Cdk2 PMID:8033212 prevents their activation, and inhibits PMID:8033212 p27Kip1 potently inhibits Rb phosphorylation by cyclin E-Cdk2, |
| GO:0000082 G1/S transition of mitotic cell cycle | IEA GO_REF:0000107 | ACCEPT | Summary: G1/S transition of mitotic cell cycle, transferred from the experimentally annotated mouse ortholog Cdkn1b (P46414). Reason: p27 acts precisely at this transition: it restrains cyclin E/A-CDK2 until CDK2-mediated Thr187 phosphorylation triggers its SCF(SKP2)-CKS1-dependent destruction, and its overexpression blocks entry into S phase. Mouse and human p27 are functionally equivalent in this role, so the orthology-based transfer is sound. Supporting Evidence: PMID:8033212 p27Kip1 overexpression obstructs cell entry PMID:16209941 Thr187 phosphorylation, which leads to the binding of the SCF(Skp2) |
| GO:0000082 G1/S transition of mitotic cell cycle | TAS Reactome:R-HSA-69206 | ACCEPT | Summary: G1/S transition, asserted by the Reactome G1/S Transition pathway in which CDKN1B is a participant. Reason: Pathway-level assertion that matches the primary literature: p27 is the CKI that gates the G1/S transition, and its degradation is a required step for S-phase entry. Redundant with the IEA row for the same term, which is acceptable. Supporting Evidence: PMID:8033212 p27Kip1 overexpression obstructs cell entry |
| GO:0004860 protein kinase inhibitor activity | IMP PMID:8684460 Crystal structure of the p27Kip1 cyclin-dependent-kinase inh... | MODIFY | Summary: Protein kinase inhibitor activity, from the crystal structure of the p27 kinase-inhibitory domain bound to phosphorylated cyclin A-CDK2. Reason: The activity is correct but stated one level too broadly. p27 does not inhibit protein kinases generally; it inhibits cyclin-dependent kinases, and the cited structure shows exactly how - the extended inhibitor binds both subunits, rearranging the CDK2 N-terminal lobe and inserting a 3(10) helix into the catalytic cleft as an ATP mimic. The specific child term GO:0004861 is the right level and is separately annotated with IDA and IBA support. Proposed replacements: cyclin-dependent protein serine/threonine kinase inhibitor activity Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity | IBA GO_REF:0000033 | ACCEPT | Summary: CDK inhibitor activity inferred from the Cip/Kip phylogeny (PANTHER:PTN004142838), with descendant evidence from Drosophila dacapo, mouse Cdkn1b, human CDKN1B itself and CDKN1C/p57. Reason: This is the defining molecular function of the Cip/Kip family and the node placement is sound: CDK-inhibitory activity is shared by p21, p27, p57 and the single invertebrate members (dacapo, cki-1/cki-2), all acting through the same bipartite cyclin-plus-CDK contact. Human P46527 appearing in its own WITH/FROM is expected and welcome - it marks that the IBD node was placed using experimental evidence that includes this gene, so the IBA adds the further claim that the activity is inherited rather than lineage-specific. Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity | IDA PMID:10918569 PTEN expression is reduced in a subset of sporadic thyroid c... | ACCEPT | Summary: CDK inhibitor activity, annotated from a study in which restored PTEN expression suppresses thyroid carcinoma cell growth through p27. Reason: The molecular function asserted is unambiguously correct for p27 and is supported many times over by direct biochemistry elsewhere in this review. The cached record for this paper is abstract-only, and the abstract reports the p27-dependence of PTEN-mediated growth suppression rather than a kinase assay, so the specific inhibition experiment is presumably in the full text the curator read; deferring to the curator is appropriate here rather than downgrading a correct function. Supporting Evidence: PMID:10918569 expression of the cyclin-dependent kinase inhibitor p27kip1 and can be overcome PMID:8033212 prevents their activation, and inhibits |
| GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity | IDA PMID:19170105 CDK inhibitors selectively diminish cell cycle controlled ac... | ACCEPT | Summary: CDK inhibitor activity shown by p27-mediated inhibition of CDK2-dependent phosphorylation of p220/NPAT and of histone H4 gene promoter activation. Reason: Direct, substrate-resolved demonstration of the core activity in cells: p27 (with p57) blocks CDK2-dependent phosphorylation of NPAT at subnuclear foci more effectively than p21, coupling CDK2 inhibition to loss of histone gene activation at the restriction point. Supporting Evidence: PMID:19170105 effective than p27(KIP1) and p57(KIP2) in inhibiting the CDK2 dependent |
| GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity | IDA PMID:28666995 Structural basis of divergent cyclin-dependent kinase activa... | ACCEPT | Summary: CDK inhibitor activity, from crystal structures of Cdk2-Spy1 and p27-Cdk2-Spy1 defining how p27 inhibits CDK2 and why Spy1/RINGO-bound CDK2 escapes it. Reason: Structurally direct and mechanistically informative: p27 inhibition requires the cyclin-binding site that Spy1 lacks, which is why p27 inhibits cyclin-CDK2 but barely inhibits CDK2-Spy1. This delimits the activity rather than contradicting it, and is the basis of the UniProt statement that p27 has little inhibitory activity on SPDYA-bound CDK2. Supporting Evidence: PMID:28666995 binding of inhibitors such as the p27 tumor suppressor PMID:28666995 explaining why Cdk-Spy1 is poorly inhibited |
| GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity | IDA PMID:8033212 Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and ... | ACCEPT | Summary: CDK inhibitor activity from the p27Kip1 cloning paper: p27 associates with cyclin E-CDK2, prevents its activation, inhibits pre-activated complexes, and blocks Rb phosphorylation by cyclin E-CDK2, cyclin A-CDK2 and cyclin D2-CDK4. Reason: The foundational direct assay for this gene's core molecular function, with the physiological context (TGF-beta- and contact-induced G1 arrest) established in the same work. Supporting Evidence: PMID:8033212 p27Kip1 associates with cyclin E-Cdk2 PMID:8033212 prevents their activation, and inhibits PMID:8033212 p27Kip1 potently inhibits Rb phosphorylation by cyclin E-Cdk2, |
| GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity | IEA GO_REF:0000120 | ACCEPT | Summary: CDK inhibitor activity from combined automated methods (ARBA rule, InterPro CDI domain IPR003175, mouse ortholog). Reason: The electronic inference agrees with direct experimental evidence and with the IBA: the CDI domain (Pfam PF02234) is the kinase-inhibitory module itself, so the InterPro-to-GO mapping is at the right level of specificity for this protein. Supporting Evidence: PMID:11790096 inhibition domain and full-length p27 are active as cyclin A-Cdk2 inhibitors. |
| GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity | TAS PMID:10208428 Comparison of the effectiveness of adenovirus vectors expres... | ACCEPT | Summary: CDK inhibitor activity, from adenoviral overexpression of p27 causing growth arrest, inhibition of DNA synthesis and loss of Rb phosphorylation in pRb-competent cells. Reason: The pRb-dependence of the arrest is a functional readout of CDK inhibition: the effect requires functional pRb, placing p27's action upstream of Rb phosphorylation, as expected for a cyclin-CDK2 inhibitor. Supporting Evidence: PMID:10208428 induced growth arrest, inhibited DNA synthesis, and prevented PMID:10208428 phosphorylation of the retinoblastoma protein (pRb) in cell lines expressing |
| GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity | TAS Reactome:R-HSA-187934 | ACCEPT | Summary: CDK inhibitor activity asserted by the Reactome reaction 'Inactivation of Cyclin A:Cdk2 complexes by p27/p21'. Reason: Reactome models the inhibitory step explicitly - p27/p21 binding inactivating cyclin A-CDK2 and cyclin E-CDK2 - which is the same assertion as the experimental rows for this term. Supporting Evidence: PMID:8033212 prevents their activation, and inhibits |
| GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity | TAS Reactome:R-HSA-69562 | ACCEPT | Summary: CDK inhibitor activity asserted by the Reactome reaction 'Inactivation of Cyclin E:Cdk2 complexes by p27/p21'. Reason: Reactome models the inhibitory step explicitly - p27/p21 binding inactivating cyclin A-CDK2 and cyclin E-CDK2 - which is the same assertion as the experimental rows for this term. Supporting Evidence: PMID:8033212 prevents their activation, and inhibits |
| GO:0005515 protein binding | IPI PMID:11961546 Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin liga... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and CUL1, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:11961546 Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. |
| GO:0005515 protein binding | IPI PMID:12082530 Interaction and colocalization of PGP9.5 with JAB1 and p27(K... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and COPS5/JAB1, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:12082530 Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1). |
| GO:0005515 protein binding | IPI PMID:12093740 A growth factor-dependent nuclear kinase phosphorylates p27(... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and UHMK1/KIS, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:12093740 A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression. |
| GO:0005515 protein binding | IPI PMID:15024385 p27 binds cyclin-CDK complexes through a sequential mechanis... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:15057270 14-3-3 suppresses the nuclear localization of threonine 157-... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and KPNA3, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:15057270 14-3-3 suppresses the nuclear localization of threonine 157-phosphorylated p27(Kip1). |
| GO:0005515 protein binding | IPI PMID:15057270 14-3-3 suppresses the nuclear localization of threonine 157-... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and KPNA5, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:15057270 14-3-3 suppresses the nuclear localization of threonine 157-phosphorylated p27(Kip1). |
| GO:0005515 protein binding | IPI PMID:15480426 Thioredoxin modulates activator protein 1 (AP-1) activity an... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and COPS5/JAB1, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:15480426 Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1. |
| GO:0005515 protein binding | IPI PMID:15652749 p27(Kip1)-stathmin interaction influences sarcoma cell migra... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and STMN1 (stathmin), recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:15652749 p27(Kip1)-stathmin interaction influences sarcoma cell migration and invasion. |
| GO:0005515 protein binding | IPI PMID:15890360 Molecular basis for the specificity of p27 toward cyclin-dep... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:15890360 Molecular basis for the specificity of p27 toward cyclin-dep... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:15890360 Molecular basis for the specificity of p27 toward cyclin-dep... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK5, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND3, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and TRAF2, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:16189514 Towards a proteome-scale map of the human protein-protein interaction network. |
| GO:0005515 protein binding | IPI PMID:16209941 Structural basis of the Cks1-dependent recognition of p27(Ki... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:16209941 Structural basis of the Cks1-dependent recognition of p27(Ki... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and SKP2, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:16209941 Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase. |
| GO:0005515 protein binding | IPI PMID:16289477 The cell cycle regulator p27Kip1 interacts with MCM7, a DNA ... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and MCM7, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:16289477 The cell cycle regulator p27Kip1 interacts with MCM7, a DNA replication licensing factor, to inhibit initiation of DNA replication. |
| GO:0005515 protein binding | IPI PMID:16326706 Shp-1 mediates the antiproliferative activity of tissue inhi... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:16326706 Shp-1 mediates the antiproliferative activity of tissue inhi... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:16431923 The nucleocapsid protein of severe acute respiratory syndrom... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:17053782 C-terminal phosphorylation controls the stability and functi... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:17053782 C-terminal phosphorylation controls the stability and functi... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and mouse Abl1, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases. |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and LYN, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases. |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:17254967 p27 phosphorylation by Src regulates inhibition of cyclin E-... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:17254967 p27 phosphorylation by Src regulates inhibition of cyclin E-... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:17418410 HIF-2alpha promotes hypoxic cell proliferation by enhancing ... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:17698606 SCAPER, a novel cyclin A-interacting protein that regulates ... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:18177895 Role of intrinsic flexibility in signal transduction mediate... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:18593906 Pim kinases promote cell cycle progression by phosphorylatin... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and PIM1, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:18593906 Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. |
| GO:0005515 protein binding | IPI PMID:18593906 Pim kinases promote cell cycle progression by phosphorylatin... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and PIM1, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:18593906 Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels. |
| GO:0005515 protein binding | IPI PMID:18692475 A protein domain-based interactome network for C. elegans ea... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:18805092 Structural insights into NEDD8 activation of cullin-RING lig... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and SKP2, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:18805092 Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. |
| GO:0005515 protein binding | IPI PMID:18805092 Structural insights into NEDD8 activation of cullin-RING lig... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and CUL1, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:18805092 Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and RHOA, recorded by curators under the bare term 'protein binding'. Reason: Here the cited paper does support a more informative molecular function, so the generic term should be replaced rather than dropped. RSK1-mediated Thr198 phosphorylation increases p27 binding to RhoA in vitro and in cells, and the consequence is measurable RhoA pathway inhibition - reduced RhoA-GTP, reduced phospho-cofilin, loss of actin stress fibres - all reversed by p27 knockdown. That is a small GTPase binding activity (GO:0031267; the former 'Rho GTPase binding' GO:0017048 has been merged into it) and it is the molecular basis of the CDK-independent cytoplasmic function of p27. Proposed replacements: small GTPase binding Supporting Evidence: PMID:19470470 increase RhoA-p27 binding and cell motility. PMID:19470470 increased motility, and reduced RhoA-GTP, phospho-cofilin, |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and RPS6KA1/RSK1, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility. |
| GO:0005515 protein binding | IPI PMID:20596027 SCF(Cyclin F) controls centrosome homeostasis and mitotic fi... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:21423214 Phosphorylation of p27Kip1 by JAK2 directly links cytokine r... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and mouse Jak2, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:21423214 Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control. |
| GO:0005515 protein binding | IPI PMID:21423803 Role of T198 modification in the regulation of p27(Kip1) pro... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and STMN1 (stathmin), recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:21423803 Role of T198 modification in the regulation of p27(Kip1) protein stability and function. |
| GO:0005515 protein binding | IPI PMID:21423803 Role of T198 modification in the regulation of p27(Kip1) pro... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:22632967 Cyclin F-mediated degradation of ribonucleotide reductase M2... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and SKP2, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:22632967 Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. |
| GO:0005515 protein binding | IPI PMID:22770219 Acetylation-dependent regulation of Skp2 function. | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and KPNA5, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:22770219 Acetylation-dependent regulation of Skp2 function. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK5, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK1, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:23602409 A NIK-IKKΞ± module expands ErbB2-induced tumor-initiating cel... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and CHUK/IKKalpha, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:23602409 A NIK-IKKΞ± module expands ErbB2-induced tumor-initiating cells by stimulating nuclear export of p27/Kip1. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK1, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK5, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding a... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding a... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK1, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding a... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding a... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and SCML2, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and TRAF2, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:25241761 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK5, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and TRAF2, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:25910212 Widespread macromolecular interaction perturbations in human genetic disorders. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and BANP, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:25910212 Widespread macromolecular interaction perturbations in human genetic disorders. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and THAP1, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:25910212 Widespread macromolecular interaction perturbations in human genetic disorders. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNB1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:26775844 Salivary protein histatin 3 regulates cell proliferation by ... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and HSPA8, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:26775844 Salivary protein histatin 3 regulates cell proliferation by enhancing p27(Kip1) and heat shock cognate protein 70 ubiquitination. |
| GO:0005515 protein binding | IPI PMID:28425505 Novel interactions of the von Hippel-Lindau (pVHL) tumor sup... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and VHL, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:28425505 Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK1, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND3, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK5, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and TRAF2, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and MTUS2, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and SPDYA/Spy1, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK1, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK5, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK1, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNB1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND3, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK5, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK1, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNB1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND3, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK5, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and FBXW7, recorded by curators under the bare term 'protein binding'. Reason: Removal reflects the term, not the data: the reported interaction may well be real, but 'protein binding' asserts nothing about what p27 does and cannot be graded as a molecular function. Per curation guidance the generic term should be replaced by an informative MF term where the paper supports one; this partner does not support a specific p27 molecular activity beyond what the CDK-inhibitory and cyclin/CDK-binding annotations already state. Supporting Evidence: PMID:35512704 Systematic discovery of mutation-directed neo-protein-protein interactions in cancer. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK2, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:8684460 Crystal structure of the p27Kip1 cyclin-dependent-kinase inh... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNA2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNB1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the kinase CDK4, recorded by curators under the bare term 'protein binding'. Reason: The interaction is well supported but the bare term is uninformative. The partner is a cyclin-dependent kinase, and the crystal structure of the p27 kinase-inhibitory domain bound to cyclin A-CDK2 shows p27 contacting and rearranging the CDK N-terminal lobe and inserting into the catalytic cleft; protein kinase binding (GO:0019901) is the evidence-backed informative replacement, with the functional consequence captured separately by GO:0004861. Proposed replacements: protein kinase binding Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCND1, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005515 protein binding | IPI PMID:9840943 Cyclin E2, a novel human G1 cyclin and activating partner of... | MODIFY | Summary: Experimental physical interaction (IPI) between p27/CDKN1B and the cyclin CCNE2, recorded by curators under the bare term 'protein binding'. Reason: The interaction data are sound, but bare 'protein binding' conveys no functional information. The partner is a cyclin, and p27 engages cyclins through a defined mechanism: its N-terminal subdomain 1 docks into the MRAIL groove of the cyclin box first, tethering the inhibitor before subdomain 2 folds onto the CDK. That is exactly cyclin binding (GO:0030332), which is the informative replacement here and is already separately annotated from PMID:15024385. Proposed replacements: cyclin binding Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: p27 is active in the nucleus, inferred across the Cip/Kip family (fly dacapo, worm cki-1, mouse Cdkn1a/Cdkn1b, human CDKN1B/CDKN1C). Reason: The nucleus is where the core activity is executed - nuclear p27 is the pool that binds cyclin E/A-CDK2 and enforces G1 restraint, and it is nuclear in G0 and early G1. The is_active_in assertion is therefore stronger and more useful than a bare located_in, and the conserved nuclear function across the family supports the node placement. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005634 nucleus | IDA PMID:11800646 Immunohistochemical analysis of p18INK4C and p14ARF protein ... | ACCEPT | Summary: Nuclear localisation of p27, annotated by immunohistochemistry in a tumour series. Reason: The localisation claim is correct and abundantly corroborated: p27 is nuclear in G0/early G1 and is imported by importin alpha3/alpha5 through a bipartite NLS. The cached record for this reference is abstract-only and its abstract reports p18INK4C and p14ARF staining, so the p27 staining data are presumably in the full text; the rule against overruling an experimental annotation on incomplete cached evidence applies, and the localisation itself is not in doubt. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears PMID:15057270 14-3-3 suppresses importin alpha/beta-dependent nuclear |
| GO:0005634 nucleus | IDA PMID:12093740 A growth factor-dependent nuclear kinase phosphorylates p27(... | ACCEPT | Summary: Nuclear localisation of p27, shown alongside the nuclear kinase KIS/UHMK1 that phosphorylates it on Ser10. Reason: Direct and well-grounded: KIS is a nuclear protein that binds the p27 C-terminus and phosphorylates Ser10 there, promoting subsequent export, so both proteins are demonstrated in the nucleus. Supporting Evidence: PMID:12093740 hKIS is a nuclear protein that binds the C-terminal domain of PMID:12093740 nuclear export to the cytoplasm |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nucleus, from combined automated methods (ARBA, UniProt subcellular location SL-0191, mouse ortholog). Reason: Consistent with the IDA and IBA rows and with the UniProt subcellular-location annotation; no conflict. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasm, from curated immunofluorescence (Human Protein Atlas). Reason: The nucleoplasm is the precise compartment for the core function and is more informative than the parent 'nucleus'; consistent with cell-cycle-dependent nuclear localisation of p27. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1226094 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Cyclin D:Cdk4/6 mediated phosphorylation of p130 (RBL2) and dissociation of phosphorylated p130 (RBL2) from DP1:E2F4/5 complex', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1226095 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Cyclin D:CDK4/6 mediated phosphorylation of p107 (RBL1) and dissociation of phosphorylated p107 (p-RBL1) from DP1:E2F4 complex', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187506 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Translocation of p27 to the nucleoplasm', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187520 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Cyclin E/A:Cdk2-mediated phosphorylation of p27/p21', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187552 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Binding of phospho-p27/p21:Cdk2:Cyclin E/A to the SCF(Skp2):Cks1 complex', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187574 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Degradation of ubiquitinated p27/p21 by the 26S proteasome', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187575 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Ubiquitination of phospho-p27/p21', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187916 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Cyclin A:Cdk2 mediated phosphorylation of p27/p21', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-187934 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Inactivation of Cyclin A:Cdk2 complexes by p27/p21', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69227 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Cyclin D:CDK4/6 phosphorylates RB1 and prevents RB1 binding to E2F1/2/3:DP1/2 complexes', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69562 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Inactivation of Cyclin E:Cdk2 complexes by p27/p21', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8942803 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'Translocation of CDK4/6:CCND complexes from the cytoplasm to the nucleus', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8942836 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'CDK4/6:CCND complexes are activated by T-loop phosphorylation of CDK4/6', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9632868 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'CDKN1B is phosphorylated in response to estrogen', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9632873 | ACCEPT | Summary: Nucleoplasm localisation asserted by the Reactome reaction 'p-S10 CDKN1B translocates to the cytosol', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: p27 is active in the cytoplasm, inferred across the Cip/Kip family. Reason: Cytoplasmic p27 is functional rather than merely mislocalised: Thr198-phosphorylated p27 binds RhoA and inhibits RhoA-ROCK signalling, and p27 binds and neutralises the microtubule-destabiliser stathmin. Family-wide is_active_in is therefore justified, and the nuclear and cytoplasmic pools are both annotated. Supporting Evidence: PMID:19470470 increased motility, and reduced RhoA-GTP, phospho-cofilin, PMID:15652749 ability to bind and impair the function of the MT-destabilizing protein |
| GO:0005737 cytoplasm | IDA PMID:12093740 A growth factor-dependent nuclear kinase phosphorylates p27(... | ACCEPT | Summary: Cytoplasmic localisation of p27 following Ser10 phosphorylation by KIS/UHMK1. Reason: Directly shown: Ser10 phosphorylation by the mitogen-activated nuclear kinase KIS promotes p27 export to the cytoplasm, which is how mitogens relieve p27-imposed arrest. Supporting Evidence: PMID:12093740 nuclear export to the cytoplasm PMID:12093740 and expression of hKIS overcomes growth arrest induced by p27(Kip1). |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasm, from combined automated methods (UniProt SL-0086, mouse ortholog). Reason: Agrees with the IDA and IBA rows; p27 is nuclear and cytoplasmic in quiescent cells and is actively exported via CRM1 in early G1. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005768 endosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Endosome, mapped from the UniProt subcellular-location vocabulary (SL-0101). Reason: The underlying UniProt statement is that p27 colocalises with SNX6 at the endosome and is thereby routed to lysosomal degradation, and it carries a 'By similarity' qualifier. Even taken at face value this is a site where p27 is disposed of rather than a compartment where it acts, so it should not be read as a functional location; retained as a non-core localisation because the underlying observation is not contradicted. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol, from curated immunofluorescence (Human Protein Atlas). Reason: Consistent with the cytoplasmic pool of p27 generated by Ser10/Thr198-dependent export and 14-3-3 binding; the cytosolic pool has documented RhoA- and stathmin-directed activities. Supporting Evidence: PMID:12093740 nuclear export to the cytoplasm PMID:19470470 increase RhoA-p27 binding and cell motility. |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Cytosol, from combined automated methods (ARBA, mouse ortholog). Reason: Redundant with the IDA row but not incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-187506 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'Translocation of p27 to the nucleoplasm', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-198613 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'AKT phosphorylates p21Cip1 and p27Kip1', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2399969 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'AKT1 E17K mutant phosphorylates p21Cip1 and p27Kip1', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8848414 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'Activated PTK6 binds CDKN1B', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8848436 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'PTK6 phosphorylates CDKN1B', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8941915 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'Cip/Kip CDK inhibitors bind CDK4/6:CCND complexes', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8942607 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'Tyrosine kinases phosphorylate Cip/Kip inhibitors bound to CDK4/6:CCND complexes', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8942803 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'Translocation of CDK4/6:CCND complexes from the cytoplasm to the nucleus', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9632873 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'p-S10 CDKN1B translocates to the cytosol', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9699575 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'FOXO3-dependent CDKN1B gene expression', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9699578 | ACCEPT | Summary: Cytosol localisation asserted by the Reactome reaction 'Active FLT3 phosphorylates CDKN1B', in which CDKN1B is a participant. Reason: Consistent with curated immunofluorescence and with p27 biology: the nuclear/nucleoplasmic pool executes cyclin E/A-CDK2 inhibition, while Ser10 phosphorylation and 14-3-3 binding to Thr198 generate the cytosolic pool. Reactome asserts one compartment per reaction, so these rows are numerous and mutually redundant, but none is incorrect. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and |
| GO:0007165 signal transduction | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Signal transduction, from an ARBA machine-learning model (ARBA00029050). Reason: p27 sits at the receiving end of signalling rather than transducing it: TGF-beta, contact inhibition, PI3K-AKT, RAS-MAPK/RSK and Src-family inputs converge on p27's synthesis, phosphorylation, localisation and degradation, and p27's own output is inhibition of cyclin-CDK complexes. A root-level 'signal transduction' term adds no information that the cell-cycle regulation terms do not already carry, and it invites propagation of an inappropriate signalling role. Not removed outright because p27 genuinely is the effector through which antimitogenic signals are relayed to the cell cycle. Supporting Evidence: PMID:8033212 a cyclin-dependent kinase inhibitor implicated in G1 phase |
| GO:0007507 heart development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Heart development, from the mouse ortholog: p21 and p27 peak around postnatal day 5 and are required for cardiomyocyte cell-cycle exit. Reason: Real but downstream and tissue-specific. p21/p27 knockout cardiomyocytes fail to exit the cycle at G1 and undergo endoreplication, so the developmental phenotype follows directly from the same cyclin E/A-CDK2 inhibitory activity annotated as core rather than representing a distinct cardiac function. Typical of the many organ-development terms a pleiotropic CKI attracts; kept, but explicitly non-core. Supporting Evidence: PMID:24380855 cyclin E, cyclin A and CDK2 at postnatal stages. PMID:24380855 showed failure in the cell cycle exit at G1-phase, and endoreplication. |
| GO:0007507 heart development | ISS PMID:24380855 CDK inhibitors, p21(Cip1) and p27(Kip1), participate in cell... | KEEP AS NON CORE | Summary: Heart development, from the mouse ortholog: p21 and p27 peak around postnatal day 5 and are required for cardiomyocyte cell-cycle exit. Reason: Real but downstream and tissue-specific. p21/p27 knockout cardiomyocytes fail to exit the cycle at G1 and undergo endoreplication, so the developmental phenotype follows directly from the same cyclin E/A-CDK2 inhibitory activity annotated as core rather than representing a distinct cardiac function. Typical of the many organ-development terms a pleiotropic CKI attracts; kept, but explicitly non-core. Supporting Evidence: PMID:24380855 cyclin E, cyclin A and CDK2 at postnatal stages. PMID:24380855 showed failure in the cell cycle exit at G1-phase, and endoreplication. |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000117 | ACCEPT | Summary: Negative regulation of cell population proliferation, from an ARBA model (ARBA00027539). Reason: Broad but squarely correct and well supported: p27 overexpression blocks S-phase entry and arrests growth across many cell types, and loss of p27 protein is a recurrent feature of epithelial tumours. An acceptable broader electronic annotation alongside the specific G1/S terms. Supporting Evidence: PMID:8033212 p27Kip1 overexpression obstructs cell entry PMID:10208428 induced growth arrest, inhibited DNA synthesis, and prevented |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:19838216 Knockdown of protein tyrosine phosphatase SHP-1 inhibits G1/... | ACCEPT | Summary: Negative regulation of proliferation, from SHP-1 knockdown in prostate carcinoma cells, which raises p27 stability and nuclear localisation and arrests cells in G1. Reason: The genetic manipulation links p27 abundance to proliferative arrest in the expected direction. The same paper notes that co-depletion of p27 does not restore cycling, so p27 is not the sole mediator in that system - which argues for keeping this at the general 'negative regulation of proliferation' level rather than reading a stronger claim into it. Supporting Evidence: PMID:19838216 increases p27(Kip1) (p27) protein stability, its nuclear localization and p27 PMID:19838216 induced by small interfering RNAs causes G1 phase cell-cycle arrest accompanied |
| GO:0019901 protein kinase binding | IPI PMID:15024385 p27 binds cyclin-CDK complexes through a sequential mechanis... | ACCEPT | Summary: Protein kinase binding: p27 binds CDK2 within the cyclin A-CDK2 complex, as the second step of a sequential, folding-on-binding mechanism. Reason: Informative and mechanistically precise. Subdomain 1 of p27 binds cyclin A first, tethering the inhibitor; subdomain 2 then binds CDK2 and folds into the kinase-inhibitory conformation. This is the CDK-contacting half of the bipartite interaction that produces GO:0004861, so the binding term earns its place rather than duplicating the activity term. Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:8684460 inserts into the catalytic cleft, mimicking ATP. |
| GO:0019903 protein phosphatase binding | IPI PMID:19838216 Knockdown of protein tyrosine phosphatase SHP-1 inhibits G1/... | KEEP AS NON CORE | Summary: Protein phosphatase binding, annotated with PTPN6/SHP-1 as partner. Reason: Phosphatases do act on p27 - PPM1H dephosphorylates Thr187 and stabilises it - so an interaction with a phosphatase is biologically plausible, and phosphatase binding is at least more informative than bare protein binding. But the cached abstract for this reference describes SHP-1 knockdown raising p27 stability and nuclear localisation, and an SHP-1-PI3K interaction, without stating a direct p27-SHP-1 complex; the binding evidence must lie in the full text. Kept on the curator's reading, but as a peripheral regulatory interaction rather than any part of p27's core function. Supporting Evidence: PMID:19838216 increases p27(Kip1) (p27) protein stability, its nuclear localization and p27 |
| GO:0019914 cyclin-dependent protein kinase regulator activity | EXP PMID:8684460 Crystal structure of the p27Kip1 cyclin-dependent-kinase inh... | ACCEPT | Summary: Cyclin-dependent protein kinase regulator activity, from the p27-cyclin A-CDK2 structure. Reason: The parent regulator term is genuinely the right shape for this protein, which is why it should not be collapsed into the inhibitor child. p27 inhibits cyclin E/A-CDK2, but it also promotes assembly of cyclin D-CDK4, directs it to the nucleus, and when phosphorylated on Tyr74/Tyr88 can permit CDK4 activity. 'Regulator' covers both signs; GO:0004861 covers the inhibitory sign and is separately annotated. Supporting Evidence: PMID:8684460 On cyclin A, it binds in a groove PMID:9106657 p21(CIP), p27(KIP), and p57(KIP2) all promote the association of cdk4 with the |
| GO:0030308 negative regulation of cell growth | IDA PMID:10208428 Comparison of the effectiveness of adenovirus vectors expres... | MODIFY | Summary: Negative regulation of cell growth, from adenoviral p27 overexpression causing arrest and inhibition of DNA synthesis. Reason: The assay measures proliferation, not growth. In GO, 'growth' is increase in size or mass of a cell, whereas what was observed - growth arrest, inhibited DNA synthesis, hypophosphorylated Rb, delayed tumour formation - is restraint of cell division. Nothing in p27 biology indicates control of cell size; the accurate term is negative regulation of cell population proliferation (GO:0008285). Proposed replacements: negative regulation of cell population proliferation Supporting Evidence: PMID:10208428 induced growth arrest, inhibited DNA synthesis, and prevented PMID:10208428 phosphorylation of the retinoblastoma protein (pRb) in cell lines expressing |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | TAS Reactome:R-HSA-6791312 | MARK AS OVER ANNOTATED | Summary: DNA damage response, signal transduction by p53 class mediator, asserted via the Reactome pathway 'TP53 Regulates Transcription of Cell Cycle Genes', in which CDKN1B appears as a participant. Reason: The p53-responsive CKI is p21/CDKN1A, not p27. Direct evidence: gamma-irradiation induces p21(CIP1/WAF1) but not p27 or p57, so p27 is not part of the p53-driven damage response even though it inhibits the same CDK2 complexes. The annotation arises from pathway membership - p27 is drawn in because 'Inactivation of Cyclin E/A:Cdk2 by p27/p21' is a sub-event of the p53-dependent G1 checkpoint - rather than from evidence that p27 transduces the damage signal. Flagged as over-annotation rather than removed, since p27 can contribute to arrest downstream of damage in some settings. Supporting Evidence: PMID:19170105 gamma-irradiation induces p21(CIP1/WAF1) but not the other two CKIs, while |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | TAS Reactome:R-HSA-69563 | MARK AS OVER ANNOTATED | Summary: DNA damage response, signal transduction by p53 class mediator, asserted via the Reactome pathway 'p53-Dependent G1 DNA Damage Response', in which CDKN1B appears as a participant. Reason: The p53-responsive CKI is p21/CDKN1A, not p27. Direct evidence: gamma-irradiation induces p21(CIP1/WAF1) but not p27 or p57, so p27 is not part of the p53-driven damage response even though it inhibits the same CDK2 complexes. The annotation arises from pathway membership - p27 is drawn in because 'Inactivation of Cyclin E/A:Cdk2 by p27/p21' is a sub-event of the p53-dependent G1 checkpoint - rather than from evidence that p27 transduces the damage signal. Flagged as over-annotation rather than removed, since p27 can contribute to arrest downstream of damage in some settings. Supporting Evidence: PMID:19170105 gamma-irradiation induces p21(CIP1/WAF1) but not the other two CKIs, while |
| GO:0030332 cyclin binding | IEA GO_REF:0000120 | ACCEPT | Summary: Cyclin binding, from combined automated methods (ARBA, mouse ortholog). Reason: Correct and central: cyclin binding via the MRAIL groove is the first and obligatory step of p27's engagement with cyclin-CDK complexes and is the main determinant of its specificity for cell-cycle CDKs. Supporting Evidence: PMID:15890360 p27/cyclin interactions are an important determinant of p27 specificity towards |
| GO:0030332 cyclin binding | IPI PMID:15024385 p27 binds cyclin-CDK complexes through a sequential mechanis... | ACCEPT | Summary: Cyclin binding, from kinetic and structural analysis of p27 binding to cyclin A within cyclin A-CDK2. Reason: Directly measured and mechanistically decisive. Rapid binding of p27 subdomain 1 to the cyclin A groove precedes and enables the slow folding of subdomain 2 onto CDK2; the same study shows p27 fails to engage p25 in CDK5-p25, which lacks the MRAIL motif, explaining why p27 regulates cell-cycle CDKs specifically. Supporting Evidence: PMID:15024385 Binding to Cdk2-cyclin A is accompanied by p27 folding, and kinetic PMID:15890360 p27 fails to interact with p25 within the |
| GO:0030332 cyclin binding | ISS PMID:24380855 CDK inhibitors, p21(Cip1) and p27(Kip1), participate in cell... | ACCEPT | Summary: Cyclin binding, inferred from the mouse ortholog: p21 and p27 bind cyclin E, cyclin A and CDK2 in postnatal cardiomyocytes. Reason: Concordant with the direct human evidence; the sequence-similarity transfer adds the in vivo, endogenous-complex context. Supporting Evidence: PMID:24380855 cyclin E, cyclin A and CDK2 at postnatal stages. |
| GO:0031464 Cul4A-RING E3 ubiquitin ligase complex | IDA PMID:21628527 Selective ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G ... | MODIFY | Summary: Annotated as part_of the CUL4A-RING E3 ubiquitin ligase complex. Reason: p27 is cargo of a cullin-4 ligase, not a subunit of it. The CRL4 complex is CUL4A/B-RBX1-DDB1 plus a DCAF substrate receptor; p27 is one of the proteins such complexes destroy - CUL4A physically interacts with p27 in Wnt-responding cells and both CUL4A and CUL4B are required for Wnt-induced p27 degradation. Note also that the cited paper's own subject is selective ubiquitylation of p21 and Cdt1 by CRL4(Cdt2). A part_of complex annotation asserts subunit composition and overstates a substrate-ligase encounter; the supportable statement is ubiquitin protein ligase binding (GO:0031625), which p27 already carries from the SCF(SKP2)-CKS1 structure. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:19056892 interacted with p27(KIP1) in Wnt-responding cells PMID:19056892 both Cul4A and Cul4B were required for Wnt-induced p27(KIP1) degradation PMID:21628527 Substrates for CRL4(Cdt2) E3 ubiquitin ligase include the replication |
| GO:0031625 ubiquitin protein ligase binding | EXP PMID:16209941 Structural basis of the Cks1-dependent recognition of p27(Ki... | KEEP AS NON CORE | Summary: Ubiquitin protein ligase binding: Thr187-phosphorylated p27 is bound by the SCF(SKP2) ligase via the accessory subunit CKS1, as shown by the Skp1-Skp2-Cks1/p27-phosphopeptide crystal structure. Reason: Structurally direct and correctly stated as binding. It belongs to how p27 is regulated rather than to what p27 does: the phospho-Thr187 side chain is read out by a CKS1 phosphate-binding site while Glu185 wedges into the SKP2-CKS1 interface, recruiting p27 for ubiquitination and destruction at G1/S. Retained as a non-core interaction that is essential context for the core inhibitory function. Supporting Evidence: PMID:16209941 phosphorylated Thr187 side chain of p27(Kip1) is recognized by a Cks1 phosphate PMID:16209941 Thr187 phosphorylation, which leads to the binding of the SCF(Skp2) |
| GO:0044877 protein-containing complex binding | IPI PMID:15024385 p27 binds cyclin-CDK complexes through a sequential mechanis... | KEEP AS NON CORE | Summary: Protein-containing complex binding, with the cyclin A-CDK2 holoenzyme (ComplexPortal CPX-2006) as the partner. Reason: Accurate and non-trivial - p27 binds the assembled binary holoenzyme rather than free subunits, which is why it can inhibit pre-activated complexes - but as a molecular function statement it is generic. The informative decomposition is already annotated: cyclin binding (GO:0030332), protein kinase binding (GO:0019901) and the resulting CDK-inhibitory activity (GO:0004861). Kept as non-core. Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8033212 prevents their activation, and inhibits |
| GO:0044877 protein-containing complex binding | IPI PMID:8684460 Crystal structure of the p27Kip1 cyclin-dependent-kinase inh... | KEEP AS NON CORE | Summary: Protein-containing complex binding, with the cyclin A-CDK2 holoenzyme (ComplexPortal CPX-2006) as the partner. Reason: Accurate and non-trivial - p27 binds the assembled binary holoenzyme rather than free subunits, which is why it can inhibit pre-activated complexes - but as a molecular function statement it is generic. The informative decomposition is already annotated: cyclin binding (GO:0030332), protein kinase binding (GO:0019901) and the resulting CDK-inhibitory activity (GO:0004861). Kept as non-core. Supporting Evidence: PMID:8684460 p27Kip1 binds the complex as an extended structure PMID:8033212 prevents their activation, and inhibits |
| GO:0045732 positive regulation of protein catabolic process | IDA PMID:19056892 A functional link between Wnt signaling and SKP2-independent... | REMOVE | Summary: Positive regulation of protein catabolic process, annotated acts_upstream_of_or_within from the study of Wnt-induced, SKP2-independent p27 turnover. Reason: The direction of the relationship is inverted: in this work p27 is the protein being catabolised, not a regulator of catabolism. Wnt signalling induces CUL4A/CUL4B, which interact with p27 and are required for its degradation and for S-phase progression. Being a substrate is not participation - the ligase and proteasome perform the proteolysis - and there is no evidence that p27 promotes turnover of any other protein. Removal concerns the annotation, not the underlying data. Supporting Evidence: PMID:19056892 Wnt-induced turnover of p27(KIP1) was independent from classical PMID:19056892 interacted with p27(KIP1) in Wnt-responding cells PMID:19056892 both Cul4A and Cul4B were required for Wnt-induced p27(KIP1) degradation |
| GO:0045740 positive regulation of DNA replication | TAS Reactome:R-HSA-69656 | MODIFY | Summary: Positive regulation of DNA replication, asserted via the Reactome pathway 'Cyclin A:Cdk2-associated events at S phase entry', in which CDKN1B participates. Reason: The sign is wrong. p27 restrains replication: it blocks cyclin E/A-CDK2, its overexpression obstructs entry into S phase, and independently of CDK inhibition its C-terminus binds MCM7 and inhibits initiation of replication. p27 appears in this Reactome pathway as the inhibitor that must be phosphorylated and destroyed for replication to begin, which is presumably how the positive sign arose. The supportable term is negative regulation of DNA replication (GO:0008156). Proposed replacements: negative regulation of DNA replication Supporting Evidence: PMID:16289477 to inhibit initiation of DNA replication PMID:16289477 inhibits DNA replication independent of its function as a PMID:8033212 p27Kip1 overexpression obstructs cell entry |
| GO:0045926 negative regulation of growth | IEA GO_REF:0000117 | MODIFY | Summary: Negative regulation of growth, from an ARBA model (ARBA00028151). Reason: Same category error as the GO:0030308 row, one level more general: the phenotypes behind this inference are reduced proliferation and arrested cell-cycle progression, not reduced cell or organism size. Negative regulation of cell population proliferation (GO:0008285) states what the evidence supports. Proposed replacements: negative regulation of cell population proliferation Supporting Evidence: PMID:8033212 p27Kip1 overexpression obstructs cell entry PMID:10208428 induced growth arrest, inhibited DNA synthesis, and prevented |
| GO:0048102 autophagic cell death | IDA PMID:12698196 Antitumour effect of cyclin-dependent kinase inhibitors (p16... | MARK AS OVER ANNOTATED | Summary: Autophagic cell death, from adenoviral overexpression of p27 in malignant glioma cell lines. Reason: The observation is real but the annotation generalises a strong-overexpression phenotype in tumour lines into a function of the gene. Adenoviral p27 suppressed growth of all glioma lines tested and induced autophagic rather than apoptotic death - yet the same construct neither reduced viability of normal astrocytes nor induced autophagy in them, so the death response is a property of the transformed context and the delivered dose. p27-null mice are viable and hyperplastic, with no indication that physiological p27 executes autophagic death. Supporting Evidence: PMID:12698196 overexpression of p27(KIP1) induced autophagic cell death, but PMID:12698196 ability to suppress the growth of all tumour cells tested than other CDKIs. |
| GO:0051168 nuclear export | IMP PMID:12529437 CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuc... | REMOVE | Summary: Nuclear export, annotated involved_in from the demonstration that p27 is exported by CRM1/Ran via a nuclear export signal. Reason: p27 is the cargo, not a component of the export machinery. CRM1 and RanGTP perform the translocation; p27 contributes only the NES that CRM1 reads, and mutating Ser10 or the NES reduces its own export. Being the transported molecule is not participating in transport - the same reasoning that keeps substrates out of the process terms of the enzymes that act on them - and p27 is not known to export any other protein. The genuine finding, that p27 localisation is cell-cycle-regulated and its export precedes cytoplasmic proteolysis, is captured by the nucleus and cytoplasm/cytosol location annotations. Supporting Evidence: PMID:12529437 p27 undergoes active, CRM1-dependent nuclear export and PMID:12529437 p27-CRM1 binding and nuclear export were inhibited by S10A mutation PMID:12529437 p27 is nuclear in G0 and early G1 and appears |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000120 | ACCEPT | Summary: Regulation of cell cycle, from combined automated methods (InterPro CDI domain, mouse ortholog). Reason: Correct, if general; the CDI domain mapping to cell-cycle regulation is appropriate for this family, and the specific G1/S terms are annotated separately. Supporting Evidence: PMID:11790096 p27(Kip1) contributes to cell-cycle regulation by inhibiting cyclin-dependent |
| GO:0051726 regulation of cell cycle | IMP PMID:12093740 A growth factor-dependent nuclear kinase phosphorylates p27(... | ACCEPT | Summary: Regulation of cell cycle, from KIS/UHMK1 experiments in which p27 is the target through which mitogens control progression. Reason: Genetically well-grounded: KIS overexpression overcomes p27-imposed arrest, KIS depletion blocks Ser10 phosphorylation and enhances arrest, and p27-null cells are refractory to KIS depletion, identifying p27 as the critical target. Supports p27 as a regulator of cell-cycle progression, here at a general level. Supporting Evidence: PMID:12093740 and expression of hKIS overcomes growth arrest induced by p27(Kip1). PMID:12093740 implicating p27(Kip1) as the |
| GO:0051726 regulation of cell cycle | ISS PMID:24380855 CDK inhibitors, p21(Cip1) and p27(Kip1), participate in cell... | ACCEPT | Summary: Regulation of cell cycle, inferred from the mouse ortholog in postnatal cardiomyocytes. Reason: Sound but general; the informative content of this paper for p27 is the G1 cell-cycle-exit phenotype, annotated elsewhere in this review. Supporting Evidence: PMID:24380855 showed failure in the cell cycle exit at G1-phase, and endoreplication. |
| GO:0060090 molecular adaptor activity | EXP PMID:8684460 Crystal structure of the p27Kip1 cyclin-dependent-kinase inh... | ACCEPT | Summary: Molecular adaptor activity, reflecting p27's non-inhibitory role in bringing CDK4 and D-type cyclins together. Reason: This is p27's second genuine molecular function, and it is why the protein cannot be described as a pure inhibitor. p21, p27 and p57 all promote association of CDK4 with D-type cyclins, increasing complex affinity mainly by lowering the off-rate, and they target the assembled cyclin D1-CDK4 to the nucleus; LaBaer et al. proposed exactly the adaptor reading. Note the annotation's own reference is the cyclin A-CDK2 inhibitory structure, so the adaptor claim rests on the assembly literature cited here rather than on that structure. Supporting Evidence: PMID:9106657 p21(CIP), p27(KIP), and p57(KIP2) all promote the association of cdk4 with the PMID:9106657 we find that all three CIP/KIP inhibitors target cdk4 and cyclin D1 to PMID:9106657 originally identified as inhibitors, may also have roles as |
| GO:0071285 cellular response to lithium ion | IDA PMID:19056892 A functional link between Wnt signaling and SKP2-independent... | MARK AS OVER ANNOTATED | Summary: Cellular response to lithium ion, annotated acts_upstream_of_or_within from experiments in which lithium was used to activate Wnt signalling. Reason: Lithium here is a pharmacological tool - a GSK3 inhibitor used to switch on Wnt signalling - and the biology under study is Wnt-induced, CUL4A/CUL4B-dependent p27 turnover. Reading the reagent into a term for the cellular response to a metal ion converts an experimental manipulation into a biological role, and p27 is the substrate whose level falls rather than an executor of any lithium response. Not removed outright because p27 abundance does demonstrably change under the treatment. Supporting Evidence: PMID:19056892 Wnt-induced turnover of p27(KIP1) was independent from classical PMID:19056892 both Cul4A and Cul4B were required for Wnt-induced p27(KIP1) degradation |
| GO:0090398 cellular senescence | TAS Reactome:R-HSA-2559583 | KEEP AS NON CORE | Summary: Cellular senescence, asserted via Reactome's Cellular Senescence pathway. Reason: Plausible and unsurprising for a CKI - stable CDK2 inhibition contributes to the senescent arrest, and p27 participates in senescence programmes in some settings - but the principal CKIs of the senescence programme are p16INK4A and p21, and this is a pathway-membership assertion rather than direct evidence for p27. Kept as a non-core process. Supporting Evidence: PMID:10208428 induced growth arrest, inhibited DNA synthesis, and prevented |
| GO:0140678 molecular function inhibitor activity | IMP PMID:11790096 Functional consequences of preorganized helical structure in... | MODIFY | Summary: Molecular function inhibitor activity, from biophysical analysis of the intrinsically disordered p27 kinase-inhibitory domain. Reason: Correct but at the top of the inhibitor hierarchy, where it says almost nothing. The cited work shows both the isolated inhibitory domain and full-length p27 acting as cyclin A-CDK2 inhibitors, and that the domain's marginally preformed helix gives a kinetic advantage in forming the inhibited complex - evidence for the specific term GO:0004861, which is the appropriate level. Proposed replacements: cyclin-dependent protein serine/threonine kinase inhibitor activity Supporting Evidence: PMID:11790096 inhibition domain and full-length p27 are active as cyclin A-Cdk2 inhibitors. PMID:11790096 p27(Kip1) contributes to cell-cycle regulation by inhibiting cyclin-dependent |
| GO:1901990 regulation of mitotic cell cycle phase transition | IEA GO_REF:0000117 | ACCEPT | Summary: Regulation of mitotic cell cycle phase transition, from an ARBA model (ARBA00029095). Reason: A correct broader parent of the G1/S-specific terms annotated elsewhere; acceptable as an electronic annotation at this level. Supporting Evidence: PMID:16209941 The ubiquitin-mediated proteolysis of the Cdk2 inhibitor p27(Kip1) plays a |
| GO:1902806 regulation of cell cycle G1/S phase transition | IMP PMID:8033212 Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and ... | ACCEPT | Summary: Regulation of the G1/S phase transition, from the cloning and functional characterisation of p27Kip1. Reason: Core process annotation, directly supported: p27 associates with cyclin E-CDK2 and prevents its activation, and its overexpression obstructs entry into S phase, with TGF-beta and cell-cell contact as the physiological triggers. Supporting Evidence: PMID:8033212 p27Kip1 associates with cyclin E-Cdk2 PMID:8033212 p27Kip1 overexpression obstructs cell entry PMID:8033212 a cyclin-dependent kinase inhibitor implicated in G1 phase |
| GO:1904706 negative regulation of vascular associated smooth muscle cell proliferation | IMP PMID:19088079 Induction of microRNA-221 by platelet-derived growth factor ... | KEEP AS NON CORE | Summary: Negative regulation of vascular smooth muscle cell proliferation, from PDGF induction of miR-221, which downregulates p27 and thereby permits vSMC proliferation. Reason: The evidence supports p27 restraining proliferation in this cell type, and the direction is right: relieving p27 is required for PDGF-driven proliferation. It is nonetheless one tissue-specific instance of the general antiproliferative function already annotated (GO:0008285), and the manipulation acts on p27 rather than through it. Kept as non-core. Supporting Evidence: PMID:19088079 down-regulation of the targets c-Kit and p27Kip1. PMID:19088079 miR-221 is critical for PDGF-mediated induction of cell proliferation. |
| GO:1905179 negative regulation of cardiac muscle tissue regeneration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of cardiac muscle tissue regeneration, from the mouse ortholog. Reason: A downstream consequence rather than a distinct activity: because p21/p27 enforce cardiomyocyte cell-cycle exit after birth, and that exit is what makes the mammalian heart refractory to regeneration by proliferation of pre-existing cardiomyocytes, loss of p27 permits continued cycling and endoreplication. Correct to record, but it is the organ-level readout of the core CDK2 inhibitory function, not a separate one. Supporting Evidence: PMID:24380855 showed failure in the cell cycle exit at G1-phase, and endoreplication. PMID:24380855 cycle exit inhibits cardiac regeneration by the proliferation of pre-existing |
| GO:1905179 negative regulation of cardiac muscle tissue regeneration | ISS PMID:24380855 CDK inhibitors, p21(Cip1) and p27(Kip1), participate in cell... | KEEP AS NON CORE | Summary: Negative regulation of cardiac muscle tissue regeneration, from the mouse ortholog. Reason: A downstream consequence rather than a distinct activity: because p21/p27 enforce cardiomyocyte cell-cycle exit after birth, and that exit is what makes the mammalian heart refractory to regeneration by proliferation of pre-existing cardiomyocytes, loss of p27 permits continued cycling and endoreplication. Correct to record, but it is the organ-level readout of the core CDK2 inhibitory function, not a separate one. Supporting Evidence: PMID:24380855 showed failure in the cell cycle exit at G1-phase, and endoreplication. PMID:24380855 cycle exit inhibits cardiac regeneration by the proliferation of pre-existing |
| GO:1990757 ubiquitin ligase activator activity | EXP PMID:16209941 Structural basis of the Cks1-dependent recognition of p27(Ki... | REMOVE | Summary: Ubiquitin ligase activator activity, annotated from the Skp1-Skp2-Cks1/phospho-p27 crystal structure. Reason: The structure establishes the opposite relationship: p27 is the substrate the ligase recognises, not an activator of it. Thr187 phosphorylation by cyclin-CDK2 creates the phosphodegron that CKS1 reads, and Glu185 inserts into the SKP2-CKS1 interface - this is how a substrate is recruited, and SCF(SKP2)-CKS1 assembles and functions on other substrates without p27. Nothing in the work shows p27 increasing ligase activity. The supportable statement from this same reference is ubiquitin protein ligase binding (GO:0031625), which is separately annotated, so no information is lost by removal. Supporting Evidence: PMID:16209941 phosphorylated Thr187 side chain of p27(Kip1) is recognized by a Cks1 phosphate PMID:16209941 Thr187 phosphorylation, which leads to the binding of the SCF(Skp2) PMID:16209941 The ubiquitin-mediated proteolysis of the Cdk2 inhibitor p27(Kip1) plays a |
| GO:2000045 regulation of G1/S transition of mitotic cell cycle | IDA PMID:10208428 Comparison of the effectiveness of adenovirus vectors expres... | MODIFY | Summary: Regulation of the G1/S transition of the mitotic cell cycle, from adenoviral p27 expression causing arrest and blocking Rb phosphorylation. Reason: The evidence is directional and the term should be too: p27 delivery arrested growth, inhibited DNA synthesis and prevented Rb phosphorylation, and the arrest required functional pRb. That is negative regulation of the G1/S transition (GO:2000134), the term already carried by IBA, and the more specific child is preferable to the sign-neutral parent here. Proposed replacements: negative regulation of G1/S transition of mitotic cell cycle Supporting Evidence: PMID:10208428 induced growth arrest, inhibited DNA synthesis, and prevented PMID:10208428 phosphorylation of the retinoblastoma protein (pRb) in cell lines expressing |
| GO:2000134 negative regulation of G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Negative regulation of the G1/S transition, inferred from the Cip/Kip phylogeny (PANTHER:PTN004142838) with descendant evidence from Drosophila dacapo and C. elegans cki-1/cki-2. Reason: This is the core process for p27 and the node placement is well judged: restraint of the G1/S transition through inhibition of G1 cyclin-CDK complexes is what dacapo and cki-1 do in flies and worms, and what p27 does in mammals, where CDK2-dependent Thr187 phosphorylation and SCF(SKP2)-CKS1 degradation form the switch that releases the block. Supporting Evidence: PMID:8033212 p27Kip1 overexpression obstructs cell entry PMID:16209941 Thr187 phosphorylation, which leads to the binding of the SCF(Skp2) |
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Download this section (compressed HTML)Q: Cytoplasmic p27 has been reported both to increase motility (RSK1/Thr198-dependent RhoA inhibition) and to decrease it (sequestration of stathmin). Which direction dominates in a given cell type, and should GO capture cytoplasmic p27's cytoskeletal role with a directional process term at all, or only as RhoA/stathmin binding plus the cytosolic location?
Suggested experts: Slingerland JM, Baldassarre G
Q: p27 acts as both inhibitor and assembly factor. Would GO be better served by an explicit 'cyclin-CDK complex assembly' molecular-function or process annotation for Cip/Kip proteins, rather than the generic molecular adaptor activity term currently used?
Suggested experts: Sherr CJ, Kriwacki RW
Q: Numerous process terms on CDKN1B (heart development, cardiac regeneration, vSMC proliferation, senescence, autophagic cell death) derive from perturbing p27 abundance. Which of these should be retained at all, given that they are consequences of one conserved activity - inhibition of G1 cyclin-CDK2 - in different tissues?
Suggested experts: Nakayama KI, Roberts JM
Experiment: Reconstitute cyclin D1-CDK4 and cyclin E-CDK2 with recombinant p27 variants (wild type, Y74F/Y88F, phosphomimetic, subdomain-1 and subdomain-2 point mutants) and measure complex assembly kinetics by surface plasmon resonance alongside kinase activity, then test the same alleles for rescue of G1 arrest and of cyclin D-CDK4 nuclear import in CDKN1B-null cells.
Hypothesis: The inhibitory and assembly-factor modes of p27 are separable, and the assembly mode requires Tyr74/Tyr88 phosphorylation rather than loss of cyclin binding.
Type: structure-function reconstitution and separation-of-function rescue
Experiment: Express compartment-restricted p27 (NLS-forced and NES-forced, in a CDK-binding-dead background) in CDKN1B-null cells and compare proximity-labelling interactomes, RhoA-GTP levels, microtubule dynamics, migration and cell-cycle distribution.
Hypothesis: Nuclear and cytoplasmic p27 have non-overlapping interactomes and phenotypes, and the cytoplasmic pool acts through RhoA and stathmin rather than through any CDK.
Type: compartment-restricted expression with proximity labelling
Experiment: Quantify CDKN1B transcript and p27 protein, with p21 as positive control, across a damage panel (ionising radiation, UV, doxorubicin) in isogenic TP53 wild-type and TP53-null cells, combined with TP53 ChIP-seq/ChIP-qPCR at the CDKN1B locus.
Hypothesis: CDKN1B is not a p53-responsive CKI, so the p53-class DNA damage response annotations reflect pathway membership rather than regulation of p27.
Type: transcriptional and protein-level damage-response profiling
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