CDKN1B encodes p27Kip1, a largely disordered Cip/Kip-family regulator that binds cyclins and cyclin-dependent kinases. Its N-terminal inhibitory region folds on cyclinβCDK complexes and restrains CDK2 activity and the G1/S transition. p27 also bridges cyclin D1 and CDK4; the assembled complex can remain inhibited, while tyrosine phosphorylation, particularly at Tyr74, alters the inhibitory contact and permits substrate-dependent CDK4 activity. Nuclear and cytoplasmic p27 pools are regulated by phosphorylation, transport and ubiquitin-dependent turnover. Cytoplasmic interactions with RhoA and stathmin link p27 to actin and microtubule regulation, with effects on motility that depend on cell context. Loss or misregulation of p27 disrupts proliferative restraint and contributes to endocrine and other tumors.
| 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: The original PMID:8033212 cloning study directly assays p27 inhibition of cyclinβCDK activity. The broader regulator term also accommodates its distinct assembly function: unphosphorylated p27 can form cyclin D1βCDK4 trimers, while phosphorylation alters inhibition and substrate-dependent catalytic activity, as directly resolved in PMID:31831640. Assembly is not synonymous with activation. |
| 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. |
| 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: |
| 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: |
| 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: Retain the PAINT inference at PTN004142838. Human p27 has direct structural and biochemical CDK-inhibitory evidence, and the inherited Cip/Kip inhibitory module is consistent with the family-level judgment. The target appearing among descendant evidence is expected and is not circular. The full ancestral reconstruction was not repeated, and no target-specific loss contradicts this activity. |
| 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 assay behind this original annotation was not independently recovered; deferring to the curator is appropriate here rather than downgrading a correct function. |
| 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: |
| 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: |
| 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 |
| 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: |
| 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: |
| 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: |
| 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: |
| GO:0005515 protein binding | IPI PMID:11961546 Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin liga... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:Q13616 supports a context-bounded non-core interaction. Reason: The source-specific CUL1 pair from PMID:11961546 was not recovered in the bounded target-record query, and its protected cache is abstract-only. Independent PMID:18805092 has an exact human CUL1βp27 enzymatic-study record, retained in the evidence extract. That corroborates the low-resolution ligase-associated interaction without claiming a direct isolated CUL1 interface or retrospectively verifying the 2002 assay. |
| GO:0005515 protein binding | IPI PMID:12082530 Interaction and colocalization of PGP9.5 with JAB1 and p27(K... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:Q92905 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q92905, and PMID:12082530: EBI-1182050, EBI-1182075. The inspected methods are anti bait coimmunoprecipitation, fluorescence microscopy. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. |
| GO:0005515 protein binding | IPI PMID:12093740 A growth factor-dependent nuclear kinase phosphorylates p27(... | MODIFY | Summary: p27 association with UniProtKB:Q8TAS1 supports protein kinase binding. Reason: Selected full Results and Figure 1B of PMID:12093740 demonstrate human hKIS/UHMK1 binding to p27; the paper also assays p27 Ser10 phosphorylation. Its endogenous co-IP in Figure 6 uses mouse fibroblasts, distinct from the human recombinant binding experiment. This is binding to the kinase UHMK1, not kinase activity supplied by p27. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:15024385 p27 binds cyclin-CDK complexes through a sequential mechanis... | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: The original primary abstract of PMID:15024385 explicitly reports sequential binding of p27 to cyclin A and CDK2. Cyclin A engagement is the first step; this is a direct source-specific basis for the cyclin-binding refinement. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:15057270 14-3-3 suppresses the nuclear localization of threonine 157-... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:O00505 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:O00505, and PMID:15057270: EBI-540571, EBI-540594, EBI-591758, EBI-591792. The inspected methods are biochemical, pull down. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. |
| GO:0005515 protein binding | IPI PMID:15057270 14-3-3 suppresses the nuclear localization of threonine 157-... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:O15131 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:O15131, and PMID:15057270: EBI-540611, EBI-540624, EBI-540640, EBI-540655, EBI-591792. The inspected methods are anti tag coimmunoprecipitation, biochemical, pull down. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. |
| GO:0005515 protein binding | IPI PMID:15480426 Thioredoxin modulates activator protein 1 (AP-1) activity an... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:Q92905 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q92905, and PMID:15480426: EBI-594810. The inspected methods are pull down. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. |
| GO:0005515 protein binding | IPI PMID:15652749 p27(Kip1)-stathmin interaction influences sarcoma cell migra... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:P16949 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P16949, and PMID:15652749: EBI-1006412. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. |
| GO:0005515 protein binding | IPI PMID:15890360 Molecular basis for the specificity of p27 toward cyclin-dep... | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P20248, and PMID:15890360: EBI-1226480, EBI-1226497, EBI-1226697, EBI-1226714, EBI-1226785, EBI-1226800. The inspected methods are footprinting, nuclear magnetic resonance, surface plasmon resonance. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:15890360 Molecular basis for the specificity of p27 toward cyclin-dep... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:15890360: EBI-1226497, EBI-1226516, EBI-1226733. The inspected methods are footprinting, surface plasmon resonance. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:15890360 Molecular basis for the specificity of p27 toward cyclin-dep... | MODIFY | Summary: p27 association with UniProtKB:Q00535 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q00535, and PMID:15890360: EBI-1226530, EBI-1226546, EBI-1226745, EBI-1226760. The inspected methods are footprinting, surface plasmon resonance. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. CDK5 association is not proof of CDK5βp25 inhibition; p27 binding specificity and inhibitory potency are distinct. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MODIFY | Summary: p27 association with UniProtKB:P30279 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P30279, and PMID:16189514: EBI-758509. The inspected methods are two hybrid pooling approach. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MODIFY | Summary: p27 association with UniProtKB:P30281 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P30281, and PMID:16189514: EBI-760261. The inspected methods are two hybrid pooling approach. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:Q12933 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q12933, and PMID:16189514: EBI-758869. The inspected methods are two hybrid pooling approach. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. |
| GO:0005515 protein binding | IPI PMID:16209941 Structural basis of the Cks1-dependent recognition of p27(Ki... | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P20248, and PMID:16209941: EBI-6860098. The inspected methods are molecular sieving. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:16209941 Structural basis of the Cks1-dependent recognition of p27(Ki... | MODIFY | Summary: p27 association with UniProtKB:Q13309 supports ubiquitin protein ligase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q13309, and PMID:16209941: EBI-6859798, EBI-6859889. The inspected methods are isothermal titration calorimetry, x-ray crystallography. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants ubiquitin protein ligase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:16289477 The cell cycle regulator p27Kip1 interacts with MCM7, a DNA ... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:P33993 supports a context-bounded non-core interaction. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P33993, and PMID:16289477: EBI-7900973, EBI-7901039, MINT-1779946, MINT-1779996. The inspected methods are pull down, two hybrid fragment pooling approach. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. |
| GO:0005515 protein binding | IPI PMID:16326706 Shp-1 mediates the antiproliferative activity of tissue inhi... | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P11802, and PMID:16326706: EBI-978118. The inspected methods are anti bait coimmunoprecipitation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:16326706 Shp-1 mediates the antiproliferative activity of tissue inhi... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:16326706: EBI-978130. The inspected methods are anti bait coimmunoprecipitation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:16431923 The nucleocapsid protein of severe acute respiratory syndrom... | MODIFY | Summary: p27 association with UniProtKB:P24385 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24385, and PMID:16431923: EBI-25746753. The inspected methods are anti bait coimmunoprecipitation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:17053782 C-terminal phosphorylation controls the stability and functi... | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P11802, and PMID:17053782: EBI-7046926, MINT-3379718. The inspected methods are anti bait coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:17053782 C-terminal phosphorylation controls the stability and functi... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P24941, and PMID:17053782: EBI-7046896, MINT-3379700. The inspected methods are anti bait coimmunoprecipitation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | MODIFY | Summary: p27 association with UniProtKB:P00520 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P00520, and PMID:17254966: EBI-1201706, EBI-1201742. The inspected methods are protein kinase assay. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The source records explicitly pair human p27 with mouse ABL1/P00520; that organism scope is preserved. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | MODIFY | Summary: p27 association with UniProtKB:P07948 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P07948, and PMID:17254966: EBI-1201624, EBI-1201690. The inspected methods are anti bait coimmunoprecipitation, protein kinase assay. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P20248, and PMID:17254966: EBI-1201766, EBI-1201786, EBI-1201829, EBI-1201881, EBI-1201901. The inspected methods are anti bait coimmunoprecipitation, molecular sieving, nuclear magnetic resonance, surface plasmon resonance. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | MODIFY | Summary: p27 association with UniProtKB:P24385 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24385, and PMID:17254966: EBI-1201861. The inspected methods are anti bait coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | MODIFY | Summary: p27 association with UniProtKB:P24864 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24864, and PMID:17254966: EBI-1201858. The inspected methods are anti bait coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:17254966: EBI-1201786, EBI-1201819. The inspected methods are surface plasmon resonance. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:17254967 p27 phosphorylation by Src regulates inhibition of cyclin E-... | MODIFY | Summary: p27 association with UniProtKB:P24864 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24864, and PMID:17254967: EBI-1201114, EBI-1201133, EBI-1201257, EBI-1201337. The inspected methods are anti bait coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:17254967 p27 phosphorylation by Src regulates inhibition of cyclin E-... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:17254967: EBI-1201114, EBI-1201133, EBI-1201257, EBI-1201327. The inspected methods are anti bait coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:17418410 HIF-2alpha promotes hypoxic cell proliferation by enhancing ... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:17418410: EBI-1236805, EBI-1238644. The inspected methods are anti bait coimmunoprecipitation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:17698606 SCAPER, a novel cyclin A-interacting protein that regulates ... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:17698606: EBI-21458188. The inspected methods are anti bait coimmunoprecipitation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:18177895 Role of intrinsic flexibility in signal transduction mediate... | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: The original PMID:18177895 study analyzes p27 bound to the CDK2βcyclin A complex with NMR, small-angle X-ray scattering and modeling. Its selected accessible text supports cyclin A contact; flexible p27 regions couple kinase regulation and phosphorylation without making p27 an enzyme. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:18593906 Pim kinases promote cell cycle progression by phosphorylatin... | MODIFY | Summary: p27 association with UniProtKB:P11309-1 supports protein kinase binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P11309-1, and PMID:18593906: EBI-10901619, EBI-10901723. The inspected methods are anti bait coimmunoprecipitation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:18593906 Pim kinases promote cell cycle progression by phosphorylatin... | UNDECIDED | Summary: The exact PIM1 long-isoform association remains unresolved. Reason: PMID:18593906 supports PIM1 regulation of p27, and exact human co-IP records for P11309-1 were inspected. The original partner here is P11309-2 (Pim-1L), which is not interchangeable with the tested short form. The target experiment for this specific isoform was not recovered, so the earlier genericity-only removal is replaced by UNDECIDED without denying a possible association. |
| GO:0005515 protein binding | IPI PMID:18692475 A protein domain-based interactome network for C. elegans ea... | MODIFY | Summary: p27 association with UniProtKB:P78396 supports cyclin binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P78396, and PMID:18692475: EBI-2000968. The inspected methods are two hybrid pooling approach. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:18805092 Structural insights into NEDD8 activation of cullin-RING lig... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:Q13309 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q13309, and PMID:18805092: EBI-2001686. The inspected methods are enzymatic study. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. |
| GO:0005515 protein binding | IPI PMID:18805092 Structural insights into NEDD8 activation of cullin-RING lig... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:Q13616 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q13616, and PMID:18805092: EBI-2001686. The inspected methods are enzymatic study. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: The original PMID:19470470 abstract and Figure 3F/G legends report p27-associated cyclin D1βCDK4 complexes in human melanoma cells. The CDK4 partner supports protein kinase binding; RSK-dependent regulation of the complex is distinct from p27 possessing kinase activity. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | MODIFY | Summary: p27 association with UniProtKB:P24864 supports cyclin binding. Reason: The exact cyclin E1 target assay from PMID:19470470 was not independently recovered. The original assertion is retained using independent exact p27βP24864 co-IP records from PMID:17254966 and PMID:17254967 and the foundational cyclin EβCDK2 study PMID:8033212. This supports the partner-class refinement without marking the 2009 source-specific experiment verified. Proposed replacements: cyclin binding Supporting Evidence: file:human/CDKN1B/CDKN1B-interaction-evidence.json |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | MODIFY | Summary: p27 association with UniProtKB:P61586 supports small GTPase binding. Reason: The original PMID:19470470 abstract and figure legends report cellular and in-vitro RhoAβp27 association, phosphorylation-dependent comparisons and p27 depletion reversing RhoA pathway and motility effects. RhoA is the small GTPase partner; no GTP hydrolysis or nucleotide exchange activity is assigned to p27. Proposed replacements: small GTPase binding |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | MODIFY | Summary: p27 association with UniProtKB:Q15418 supports protein kinase binding. Reason: The original PMID:19470470 abstract and Figure 3A/B legends show RSK1 co-immunoprecipitating with p27 in human melanoma cells. Its phosphorylation of p27 is also measured. This supports binding to RSK1 as a kinase, not transfer of RSK1 catalytic activity to p27. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:20596027 SCF(Cyclin F) controls centrosome homeostasis and mitotic fi... | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: The exact p27βcyclin A2 supplementary target record in PMID:20596027 was not independently inspected. The same canonical pair is established by the original structural study PMID:8684460 and sequential binding measurements in PMID:15024385. Retain the evidence-backed cyclin-binding refinement with this independent provenance explicit, without calling the CP110/cyclin F paper wrong or its target experiment verified. Proposed replacements: cyclin binding Supporting Evidence: file:human/CDKN1B/CDKN1B-interaction-evidence.json |
| GO:0005515 protein binding | IPI PMID:21423214 Phosphorylation of p27Kip1 by JAK2 directly links cytokine r... | MODIFY | Summary: p27 association with UniProtKB:Q62120 supports protein kinase binding. Reason: Selected full Results and Figure 3 of PMID:21423214 show recombinant p27βJAK2 pull-down, reciprocal co-IP in transfected 293T cells and endogenous association in Ba/F3 and HEL cells. Methods explicitly use a mouse JAK2 kinase-domain preparation, consistent with preserved partner Q62120. Human-cell context is not used to relabel that mouse partner. Binding to a kinase is supported; p27 is the regulated substrate. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:21423803 Role of T198 modification in the regulation of p27(Kip1) pro... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:P16949 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P16949, and PMID:21423803: EBI-12739477, EBI-12739491. The inspected methods are anti bait coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. |
| GO:0005515 protein binding | IPI PMID:21423803 Role of T198 modification in the regulation of p27(Kip1) pro... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:21423803: EBI-12737598. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:22632967 Cyclin F-mediated degradation of ribonucleotide reductase M2... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:Q13309 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q13309, and PMID:22632967: EBI-6162996. The inspected methods are pull down. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. |
| GO:0005515 protein binding | IPI PMID:22770219 Acetylation-dependent regulation of Skp2 function. | KEEP AS NON CORE | Summary: p27 association with UniProtKB:O15131 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:O15131, and PMID:22770219: EBI-6262828. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:23455922: EBI-6255891. The inspected methods are tandem affinity purification. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MODIFY | Summary: p27 association with UniProtKB:Q00535 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q00535, and PMID:23455922: EBI-6256270. The inspected methods are tandem affinity purification. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. CDK5 association is not proof of CDK5βp25 inhibition; p27 binding specificity and inhibitory potency are distinct. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p... | MODIFY | Summary: p27 association with UniProtKB:P06493 supports protein kinase binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P06493, and PMID:23543736: EBI-28996916. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p... | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P11802, and PMID:23543736: EBI-27122099. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:23602409 A NIK-IKKΞ± module expands ErbB2-induced tumor-initiating cel... | MODIFY | Summary: p27 association with UniProtKB:O15111 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:O15111, and PMID:23602409: EBI-6862770, EBI-6862856, EBI-6862900, EBI-6862940. The inspected methods are protein kinase assay. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: p27 association with UniProtKB:P06493 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P06493, and PMID:23602568: EBI-6380166. The inspected methods are tandem affinity purification. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P11802, and PMID:23602568: EBI-6380178. The inspected methods are tandem affinity purification. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:23602568: EBI-6380188. The inspected methods are tandem affinity purification. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MODIFY | Summary: p27 association with UniProtKB:Q00535 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q00535, and PMID:23602568: EBI-6380843. The inspected methods are tandem affinity purification. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. CDK5 association is not proof of CDK5βp25 inhibition; p27 binding specificity and inhibitory potency are distinct. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding a... | MODIFY | Summary: p27 association with UniProtKB:O96020 supports cyclin binding. Reason: Selected full Results, Figure 1 and supplementary legends of PMID:24358021 identify human p27, cyclin E2 and CDK components in a purified SCML2B-associated complex and co-elution. This supports the cyclin E2 association at complex resolution; it does not by itself map an isolated p27βcyclin E2 interface. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding a... | MODIFY | Summary: p27 association with UniProtKB:P06493 supports protein kinase binding. Reason: Selected full PMID:24358021 Results and recombinant-complex experiments support p27 association with CDK1-containing cyclin complexes. The refinement describes the kinase partner; co-purification is not a separate direct-contact measurement or proof of inhibition of every CDK1 complex. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding a... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Selected full PMID:24358021 Results, Figure 1 and recombinant-complex experiments support p27 association with CDK2-containing cyclin complexes. The refinement describes the kinase partner and retains the complex-associated resolution of the original experiments. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding a... | UNDECIDED | Summary: SCML2B-associated complexes are established, but the original accession-to-construct mapping is unresolved. Reason: Full PMID:24358021 Results identify p27 in SCML2B-containing complexes and distinguish SCML2B from the SPM-domain-containing SCML2A. The original partner is Q9UQR0-1, currently the displayed 700-residue protein; the retrieved UniProt isoform entries do not securely map the paper's SCML2B construct to that exact accession. Retain the original source assertion while leaving this isoform-specific judgment unresolved; gene-level complex association alone does not settle it. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P11802, and PMID:25241761: EBI-6593121. The inspected methods are proximity ligation assay. Proximity ligation reports proximity in the assayed cells, not an isolated binary interface. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: p27 association with UniProtKB:P24864 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24864, and PMID:25241761: EBI-6593286. The inspected methods are proximity ligation assay. Proximity ligation reports proximity in the assayed cells, not an isolated binary interface. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:25241761: EBI-6593264. The inspected methods are proximity ligation assay. Proximity ligation reports proximity in the assayed cells, not an isolated binary interface. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:Q12933 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q12933, and PMID:25241761: EBI-6591834. The inspected methods are proximity ligation assay. Proximity ligation reports proximity in the assayed cells, not an isolated binary interface. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:25852190: EBI-10103120, EBI-10103136. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MODIFY | Summary: p27 association with UniProtKB:Q00535 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q00535, and PMID:25852190: EBI-10103156. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. CDK5 association is not proof of CDK5βp25 inhibition; p27 binding specificity and inhibitory potency are distinct. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MODIFY | Summary: The CCND2 association supports cyclin binding with explicit assay and variant scope. Reason: Publisher Table S3A of PMID:25910212 scores the human CDKN1B I119TβCCND2 Y2H pair positive and wild type zero; feature-free pooling records are not separate WT positives. Table S3B independently reports similar high CCND2 split-luciferase complementation values for WT and I119T p27 (6.903 and 6.962). This supports cyclin binding in the tested contexts, without importing the cyclin A/CDK2 structural interface or claiming a Y2H-negative result excludes all WT binding. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | KEEP AS NON CORE | Summary: The screen supports an I119T-dependent p27 association with TRAF2. Reason: Actual publisher Table S3A of PMID:25910212 reports I119T CDKN1B positive and WT zero in Y2H with TRAF2; S3C identifies gain of interaction. Exact partner/isoform records are preserved in the extract. Retain this observed mutant-context capability as non-core under the project instruction, without presenting it as WT physiology. Feature-free pooling records are not independent WT confirmation, and numeric GPCA scores are not assigned an invented binary threshold. Independent PMID:31515488 additionally supports the TRAF2 pair in its own variant-comparison context. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | KEEP AS NON CORE | Summary: The screen supports an I119T-dependent p27 association with BANP isoform Q8N9N5-2. Reason: Actual publisher Table S3A of PMID:25910212 reports I119T CDKN1B positive and WT zero in Y2H with BANP isoform Q8N9N5-2; S3C identifies gain of interaction. Exact partner/isoform records are preserved in the extract. Retain this observed mutant-context capability as non-core under the project instruction, without presenting it as WT physiology. Feature-free pooling records are not independent WT confirmation, and numeric GPCA scores are not assigned an invented binary threshold. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | KEEP AS NON CORE | Summary: The screen supports an I119T-dependent p27 association with THAP1. Reason: Actual publisher Table S3A of PMID:25910212 reports I119T CDKN1B positive and WT zero in Y2H with THAP1; S3C identifies gain of interaction. Exact partner/isoform records are preserved in the extract. Retain this observed mutant-context capability as non-core under the project instruction, without presenting it as WT physiology. Feature-free pooling records are not independent WT confirmation, and numeric GPCA scores are not assigned an invented binary threshold. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: p27 association with UniProtKB:P14635 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P14635, and PMID:26496610: EBI-11103574. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P20248, and PMID:26496610: EBI-11103410. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: p27 association with UniProtKB:P24385 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24385, and PMID:26496610: EBI-11132222. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:26496610: EBI-11106375, EBI-11151969. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:26775844 Salivary protein histatin 3 regulates cell proliferation by ... | MODIFY | Summary: p27 association with UniProtKB:P11142 supports Hsp70 protein binding. Reason: The original PMID:26775844 abstract explicitly reports interaction of p27 with HSC70 in human gingival fibroblasts, enhanced by histatin-3 in a sequence-dependent comparison. HSPA8/P11142 is an Hsp70-family chaperone, supporting GO:0030544. This is chaperone binding by a regulated client, not evidence that p27 is itself a chaperone or co-chaperone. Proposed replacements: Hsp70 protein binding |
| GO:0005515 protein binding | IPI PMID:28425505 Novel interactions of the von Hippel-Lindau (pVHL) tumor sup... | KEEP AS NON CORE | Summary: p27 association with UniProtKB:P40337 supports a context-bounded non-core interaction. Reason: Selected full PMID:28425505 Results and Figure 2 report human pVHL30βp27 yeast two-hybrid and tagged HEK293T co-IP. Figure 4 compares VHL forms and interaction-altering mutations. Retain the observed association as non-core; this evidence does not establish an E3 catalytic or substrate-recognition activity performed by p27. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: p27 association with UniProtKB:P06493 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P06493, and PMID:28514442: EBI-21808731. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P11802, and PMID:28514442: EBI-21835664. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P20248, and PMID:28514442: EBI-21770687. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: p27 association with UniProtKB:P24385 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24385, and PMID:28514442: EBI-21832810. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:28514442: EBI-21606933. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: p27 association with UniProtKB:P30279 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P30279, and PMID:28514442: EBI-21848702. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: p27 association with UniProtKB:P30281 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P30281, and PMID:28514442: EBI-21832877. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: p27 association with UniProtKB:Q00535 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q00535, and PMID:28514442: EBI-21607072. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. CDK5 association is not proof of CDK5βp25 inhibition; p27 binding specificity and inhibitory potency are distinct. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec... | MODIFY | Summary: p27 association with UniProtKB:P78396 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P78396, and PMID:29997244: EBI-20733256, EBI-20733526, EBI-20735441, EBI-20735621. The inspected methods are bioluminescence resonance energy transfer, luminescence based mammalian interactome mapping. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: The TRAF2 pair is supported in a defined human variant-comparison screen. Reason: The exact PMID:31515488 record EBI-22132299 matches human p27 and TRAF2 and records ten p27 mutation-with-no-effect positions in two-hybrid comparisons. The full cached Methods explicitly compare WT and mutant ORFs. Retain this source-bounded non-core association; position-only fields are not used to invent amino-acid substitutions. This is independent corroboration, not retrospective proof that the 2015 WT Y2H pair was positive. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: p27 association with UniProtKB:Q5JR59-3 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q5JR59-3, and PMID:32296183: EBI-22984412, EBI-24390729, EBI-24851103. The inspected methods are two hybrid array, two hybrid prey pooling approach, validated two hybrid. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: p27 association with UniProtKB:Q5MJ70 supports a context-bounded non-core interaction. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q5MJ70, and PMID:32296183: EBI-23886968, EBI-24178405, EBI-24786296. The inspected methods are two hybrid array, two hybrid prey pooling approach, validated two hybrid. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. Retain the supported association as non-core under the explicit project instruction; no more specific molecular activity is established by this evidence. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: p27 association with UniProtKB:P06493 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P06493, and PMID:32707033: EBI-28931624. The inspected methods are pull down. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P11802, and PMID:32707033: EBI-28931921. The inspected methods are pull down. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MODIFY | Summary: p27 association with UniProtKB:Q00535 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q00535, and PMID:32707033: EBI-28938854. The inspected methods are pull down. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. CDK5 association is not proof of CDK5βp25 inhibition; p27 binding specificity and inhibitory potency are distinct. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: p27 association with UniProtKB:P78396 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P78396, and PMID:32814053: EBI-26296426. The inspected methods are luminescence based mammalian interactome mapping. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:O96020 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:O96020, and PMID:33961781: EBI-54668659, EBI-54975116. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:P06493 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P06493, and PMID:33961781: EBI-54723636, EBI-54975116, EBI-55011746. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P11802, and PMID:33961781: EBI-54742707, EBI-54975116. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:P14635 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P14635, and PMID:33961781: EBI-54755182, EBI-54975116. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P20248, and PMID:33961781: EBI-54693462, EBI-54936245, EBI-55009653. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:P24385 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24385, and PMID:33961781: EBI-54762584, EBI-54978670. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:P24864 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24864, and PMID:33961781: EBI-54668659, EBI-54975116. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24941, and PMID:33961781: EBI-54723664, EBI-54975004, EBI-55011666. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:P30279 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P30279, and PMID:33961781: EBI-54753541, EBI-54978640. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:P30281 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P30281, and PMID:33961781: EBI-54740568, EBI-54975116, EBI-55014249. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:P78396 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P78396, and PMID:33961781: EBI-54668659. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: p27 association with UniProtKB:Q00535 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:Q00535, and PMID:33961781: EBI-54722283, EBI-54975116, EBI-55008419. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. CDK5 association is not proof of CDK5βp25 inhibition; p27 binding specificity and inhibitory potency are distinct. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: p27 association with UniProtKB:O96020 supports cyclin binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:O96020, and PMID:34591612: EBI-34580742. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: p27 association with UniProtKB:P06493 supports protein kinase binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P06493, and PMID:34591612: EBI-34580742. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P11802, and PMID:34591612: EBI-34580742, EBI-34581818. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: p27 association with UniProtKB:P14635 supports cyclin binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P14635, and PMID:34591612: EBI-34580742, EBI-34581818. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P20248, and PMID:34591612: EBI-34580742. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: p27 association with UniProtKB:P24385 supports cyclin binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P24385, and PMID:34591612: EBI-34580742, EBI-34581818. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: p27 association with UniProtKB:P24864 supports cyclin binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P24864, and PMID:34591612: EBI-34580742, EBI-34581818. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P24941, and PMID:34591612: EBI-34580742, EBI-34581818. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: p27 association with UniProtKB:P30281 supports cyclin binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P30281, and PMID:34591612: EBI-34580732, EBI-34580742, EBI-34581722, EBI-34581818. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: p27 association with UniProtKB:Q00535 supports protein kinase binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:Q00535, and PMID:34591612: EBI-34580742, EBI-34581818. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. CDK5 association is not proof of CDK5βp25 inhibition; p27 binding specificity and inhibitory potency are distinct. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MODIFY | Summary: p27 association with UniProtKB:P24385 supports cyclin binding. Reason: Exact source-linked MINT records match CDKN1B/P46527, UniProtKB:P24385, and PMID:34591642: EBI-34584043, EBI-34585018, EBI-44457706. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: The released official OpenCell table contains CDK2 bait ENSG00000123374 with CDKN1B prey ENSG00000111276, protein group P46527;H7C2T1;E7ES52. The exact numerical target row and dataset hash are retained in the evidence extract. This is affinity-purification association with a kinase and does not resolve the prey isoform, a purified binary interface, or inhibition in that screen. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | KEEP AS NON CORE | Summary: Human p27 associates with tested FBXW7 variants in proximity and pull-down assays. Reason: Exact PMID:35512704 records place the mutations on FBXW7/Q969H0, not p27. Four BRET records report no change at partner positions 465, 479 or 505; a pull-down record reports increased association at 465. Selected primary Methods use tagged human proteins in HEK293T lysates. Retain the observed association as non-core without claiming native WT/WT affinity, a purified binary interface, or ligase activity performed by p27. Target supplemental images were not inspected; the assessment uses exact curated records and inspected main assay context. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: p27 association with UniProtKB:P24385 supports cyclin binding. Reason: The exact target supplementary record from PMID:40205054 was not independently recovered. Independent PMID:9106657 establishes the canonical human p27βcyclin D1/CDK4 assembly, with positive exact P24385 records also present in BioPlex. The cyclin-binding refinement is therefore supported holistically while the 2025 source-specific experiment remains unverified. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: p27 association with UniProtKB:P24941 supports protein kinase binding. Reason: The exact target supplementary record from PMID:40205054 was not independently recovered. Independent structural and binding studies PMID:8684460 and PMID:15024385 establish p27βCDK2 contact, and exact CDK2 associations occur in the inspected screens. Retain protein kinase binding with that independent provenance explicit; do not claim the 2025 target experiment was inspected. Proposed replacements: protein kinase binding Supporting Evidence: file:human/CDKN1B/CDKN1B-interaction-evidence.json |
| GO:0005515 protein binding | IPI PMID:8684460 Crystal structure of the p27Kip1 cyclin-dependent-kinase inh... | MODIFY | Summary: p27 association with UniProtKB:P20248 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P20248, and PMID:8684460: EBI-1026119. The inspected methods are x-ray crystallography. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C... | MODIFY | Summary: p27 association with UniProtKB:P14635 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P14635, and PMID:8756624: EBI-519593. The inspected methods are pull down. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C... | MODIFY | Summary: p27 association with UniProtKB:P24864 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24864, and PMID:8756624: EBI-519585. The inspected methods are pull down. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | MODIFY | Summary: p27 association with UniProtKB:P11802 supports protein kinase binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P11802, and PMID:9106657: EBI-519297. The inspected methods are anti bait coimmunoprecipitation. The supported partner class warrants protein kinase binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: protein kinase binding |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | MODIFY | Summary: p27 association with UniProtKB:P24385 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:P24385, and PMID:9106657: EBI-519440. The inspected methods are anti tag coimmunoprecipitation. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| GO:0005515 protein binding | IPI PMID:9840943 Cyclin E2, a novel human G1 cyclin and activating partner of... | MODIFY | Summary: p27 association with UniProtKB:O96020 supports cyclin binding. Reason: Exact source-linked IntAct records match CDKN1B/P46527, UniProtKB:O96020, and PMID:9840943: EBI-1245805, EBI-1245823. The inspected methods are anti bait coimmunoprecipitation, two hybrid. Tagged, fragment or mutation features are preserved in the durable extract; feature-free rows are not assumed to be independent wild-type confirmation. The supported partner class warrants cyclin binding. This does not assign the partner's catalytic activity to p27 or assert a new downstream function. These assays can detect a complex-associated interaction and do not alone establish purified direct contact. Proposed replacements: cyclin binding |
| 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: Retain the PAINT nuclear-function inference, corroborated by nuclear p27 localization and its cyclinβCDK inhibitory function. Human p27's own source evidence does not make the phylogenetic assertion circular; no target-specific loss is apparent. Supporting Evidence: |
| 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 exact p27 staining experiment was not independently recovered from the abstract; the rule against overruling an experimental annotation on incomplete cached evidence applies, and the localisation itself is not in doubt. |
| 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: |
| 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: |
| 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: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: p27 is active in the cytoplasm, inferred across the Cip/Kip family. Reason: Retain the PAINT cytoplasmic-function inference. Human p27 has experimentally supported cytoplasmic RhoA-associated regulation and stathmin interactions, so this is not explained solely by disposal of exported protein. The full ancestral reconstruction was not repeated. |
| 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: |
| 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: |
| 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. |
| 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: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| 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: The original Reactome event assigns p27 to this compartment in a curated cell-cycle or regulatory reaction. Retain the location as corroborated by the experimentally documented nuclear and cytoplasmic pools. Reaction context does not by itself make every enclosing pathway a process executed by p27. Supporting Evidence: |
| GO:0007165 signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: p27 couples regulatory signals to cyclinβCDK and cytoskeletal outputs. Reason: The old rationale treated an intracellular effector as categorically outside signal transduction. GO:0007165 does not impose that exclusion. Direct conformational and phosphorylation-dependent changes in p27 alter cyclinβCDK activity, and RhoA-associated effects provide another functional output. Retain the broad electronic assertion as non-core; the more precise inhibitory and adaptor functions organize the core. |
| 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: |
| 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: |
| 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. |
| 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 broad antiproliferative function is independently established by p27 inhibitory and S-phase-entry experiments. The PMID:19838216 abstract reports p27 accumulation after SHP-1 depletion, but p27 codepletion does not restore cycling in that setting; it therefore does not establish p27 as the required mediator of that arrest. Retain the biologically correct function with independent PMID:8033212/10208428 support, without overstating the original perturbation result. |
| 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. |
| GO:0019903 protein phosphatase binding | IPI PMID:19838216 Knockdown of protein tyrosine phosphatase SHP-1 inhibits G1/... | UNDECIDED | Summary: The original SHP-1/p27 phosphatase-binding assertion remains unverified. Reason: The accessible PMID:19838216 abstract reports SHP-1 depletion affecting p27 abundance and localization and explicitly describes SHP-1βPI3K association. It does not resolve the exact p27βPTPN6/P29350 binding experiment, and the bounded full-text retrieval did not recover it. A different phosphatase acting on p27 cannot establish this original partner claim. Preserve the IPI source and use UNDECIDED rather than either a wrong-source removal or unsupported confirmation. Supporting Evidence: |
| 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 regulator assertion is correct: p27 inhibits cyclinβCDK2 and also supports cyclin D1βCDK4 assembly with phosphorylation-dependent changes in catalytic state. The current ontology graph places the specific CDK inhibitor under GO:0016538 and GO:0019914; the latter's inconsistent activating-kinase definition is not used as a biological disproof. PMID:8684460 establishes the inhibitory structural mode, while independent PMID:31831640 resolves the assembly/activity distinction. |
| 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 accessible PMID:10208428 abstract reports cell-cycle arrest, inhibited DNA synthesis, Rb hypophosphorylation and delayed tumor formation after CKI delivery. These readouts support restraint of cell population proliferation, rather than a measured decrease in individual-cell size. Refine this source-specific assertion accordingly, without claiming that p27 cannot influence organismal growth in other experiments. Proposed replacements: negative regulation of cell population proliferation Supporting Evidence: |
| 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 Reactome pathway includes the p27/p21 cyclinβCDK inhibitory event within a p53-dependent checkpoint. That shared inhibitor context is not itself evidence of a p27-specific p53 signal-transduction step. PMID:19170105 reports gamma-irradiation induction of p21 but not p27/p57 in its tested setting. Retain an over-annotation flag for the pathway-level inference, without asserting that p27 can never contribute to DNA-damage arrest or that lack of transcriptional induction alone excludes participation. Supporting Evidence: |
| 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 Reactome pathway includes the p27/p21 cyclinβCDK inhibitory event within a p53-dependent checkpoint. That shared inhibitor context is not itself evidence of a p27-specific p53 signal-transduction step. PMID:19170105 reports gamma-irradiation induction of p21 but not p27/p57 in its tested setting. Retain an over-annotation flag for the pathway-level inference, without asserting that p27 can never contribute to DNA-damage arrest or that lack of transcriptional induction alone excludes participation. Supporting Evidence: |
| 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: |
| 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. |
| 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: |
| GO:0031464 Cul4A-RING E3 ubiquitin ligase complex | IDA PMID:21628527 Selective ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G ... | UNDECIDED | Summary: The exact basis for p27 membership in a Cul4A ligase complex is unresolved. Reason: Selected actual PMID:21628527 Methods and Results describe Cdt2 affinity purification and CRL4 assays, but the target p27 evidence behind this original complex annotation was not recovered. The title's focus on other substrates is not a reason to reject it. Independent PMID:19056892 reports CUL4-associated p27 turnover, but a substrate encounter does not by itself establish the original complex-membership claim. Retain the source tuple and leave this judgment unresolved. |
| 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: |
| 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: The cited assays establish p27 binding to assembled cyclin AβCDK2, without ruling out binding to free subunits in other contexts. Retain the complex-binding assertion as non-core because its informative components are separately represented by cyclin binding, kinase binding and CDK-inhibitory activity. |
| 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: The cited assays establish p27 binding to assembled cyclin AβCDK2, without ruling out binding to free subunits in other contexts. Retain the complex-binding assertion as non-core because its informative components are separately represented by cyclin binding, kinase binding and CDK-inhibitory activity. |
| GO:0045732 positive regulation of protein catabolic process | IDA PMID:19056892 A functional link between Wnt signaling and SKP2-independent... | REMOVE | Summary: The source measures CUL4-dependent p27 turnover, not catabolism promoted by p27. Reason: The complete primary PMID:19056892 Results, Figure 6 and transfection Methods were accessed externally. Human 293T experiments vary Wnt10b/CUL4A and measure turnover of human p27 WT/T187A, while the KR5 substrate mutant is resistant. Figure 6G recovers p27 with CUL4A and Figure 6H measures p27 depletion; CUL4A/B dominant-negative experiments in MCF7 restore p27. These assays establish CUL4-dependent catabolism acting on p27, not a catalytic or cofactor activity supplied by p27 that increases proteolysis. Remove this source-specific regulator assertion without claiming that a substrate can never also regulate degradation. Supporting Evidence: 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: Reactome R-HSA-69656 places p27 within cyclin AβCDK2-associated S-phase-entry events. Its actual inhibitory contribution restrains replication; release of that restraint by phosphorylation and destruction is not a positive activity performed by p27. Independent PMID:16289477 reports p27 C-terminal binding to MCM7 and inhibition of replication initiation, supporting the negative-regulation replacement. Preserve the original pathway source while distinguishing the inhibitor from its removal. Proposed replacements: negative regulation of DNA replication |
| GO:0045926 negative regulation of growth | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: p27 limits organismal growth through its restraint of cell proliferation. Reason: GO:0045926 includes the increase in size or mass of all or part of an organism and is broader than individual-cell growth. Independent primary mouse evidence in PMID:8646780 reports enlarged animals after disruption of the p27 inhibitory domain, attributed to increased cell number and proliferation. Retain this broad conserved regulatory role as non-core with the species scope explicit. It does not imply reduced size of each cell or independently reconstruct the ARBA rule. |
| 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: Selected full PMID:12698196 Methods and Results test adenoviral human p27 expression in human glioma cell lines. Loss of viable cells and acidic vesicle accumulation were measured, with little TUNEL positivity; the normal astrocyte comparator is rat RNB. These data support a context-dependent association between p27 overexpression and death with autophagic features, but the inspected experiments do not establish that p27 supplies the autophagic execution step or that autophagy is required for death. Mark the process over-annotated on this mechanistic/assay boundary, not merely because the experiment uses tumor cells or overexpression. Supporting Evidence: PMID:12698196 overexpression of p27(KIP1) induced autophagic cell death |
| 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: Selected full PMID:12529437 Methods and Results, including Figures 2, 3 and 6, measure export of human p27 itself from MCF-7 nuclei. CRM1/Ran-dependent transport and altered export of p27 NES/S10 mutants establish p27 as the transported cargo in these assays. No export-promoting scaffold or cofactor role performed by p27 is established in the inspected experiments. Remove this process assertion on that source-specific participation boundary, while retaining the demonstrated localization and binding findings; this is not a universal claim that cargo proteins can never also regulate transport. Figure 6 additionally grafts the p27 NES onto FITC-BSA and exports that fusion. This demonstrates a transferable cargo-recognition signal, not native p27 transporting a separate cargo molecule. Supporting Evidence: PMID:12529437 p27-CRM1 binding and nuclear export were inhibited by S10A mutation |
| 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: |
| 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: |
| 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: |
| 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: Retain the adaptor function, supported by independent PMID:9106657 cyclin DβCDK4 assembly/nuclear-targeting results and the direct human trimer experiments in PMID:31831640. Unphosphorylated p27 can bridge cyclin D1 and CDK4 while inhibiting the kinase. Phosphorylation, particularly at Tyr74, changes that inhibitory contact and permits substrate-dependent activity without dissociation. The original PMID:8684460 inhibitory cyclin AβCDK2 structure is preserved as the source; it is not alone treated as the CDK4 assembly assay. |
| GO:0071285 cellular response to lithium ion | IDA PMID:19056892 A functional link between Wnt signaling and SKP2-independent... | KEEP AS NON CORE | Summary: Lithium treatment elicits p27 turnover in the assayed human cells. Reason: Complete primary PMID:19056892 Results and Figure 3C compare human 293T cells expressing human Flag-p27 WT/T187A after 25/50 mM LiCl versus 50 mM NaCl control. Both p27 forms decline; Results also describe LiCl-linked CUL4A induction and p27 turnover in MCF7. GO:0071285 permits pharmacological stimuli, so the old reagent-based exclusion was invalid. Retain this contextual response as non-core, without claiming lithium sensing or binding by p27, p27-specific necessity, or a newly demonstrated mechanistic response activity. Supporting Evidence: |
| 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: |
| 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: |
| 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: |
| 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: |
| 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: |
| 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: Retain as a non-core consequence of the conserved cell-cycle restraint in cardiomyocytes. The PMID:24380855 mouse study reports failure of G1 exit and endoreplication after p21/p27 loss; the authors connect this barrier to limited cardiac regeneration. This is mouse ortholog evidence and an organ-level interpretation, not a direct demonstration that human p27 independently executes a regenerative program. Supporting Evidence: |
| 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: Retain as a non-core consequence of the conserved cell-cycle restraint in cardiomyocytes. The PMID:24380855 mouse study reports failure of G1 exit and endoreplication after p21/p27 loss; the authors connect this barrier to limited cardiac regeneration. This is mouse ortholog evidence and an organ-level interpretation, not a direct demonstration that human p27 independently executes a regenerative program. Supporting Evidence: |
| 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: Selected full Results, Figure 4 and Methods of PMID:16209941 establish phosphodegron recognition and ubiquitination of p27 as the tested substrate. Purified SCF(SKP2)βCKS1 is assembled before phosphorylated p27 is added; the readout is p27 ubiquitin conjugates, and recognition-interface mutations impair that substrate reaction. These experiments do not establish p27 as a ligase activator distinct from its substrate role. Remove only this activator assertion, preserving the independently represented ligase-binding interaction. This is not a universal assertion that a substrate cannot also regulate a ligase. Supporting Evidence: |
| 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: |
| 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: Retain the PAINT negative G1/S regulation inference. Direct human p27 inhibition and S-phase-entry experiments independently corroborate this inherited regulatory role. Donor count is not treated as a measure of PAINT strength, and no target-specific divergence refutes the assertion. |
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Download this section (compressed HTML)Q: How do p27 phosphorylation stoichiometry, substrate docking and cell compartment jointly determine whether assembled cyclin DβCDK4 complexes inhibit or promote a particular phosphorylation event?
Q: Which cellular contexts favor RhoA-associated versus stathmin-associated p27 effects on motility, and how do these relate to its nuclear antiproliferative activity?
Q: Can the original source experiments resolve the PIM1 long isoform, SCML2 accession-to-construct mapping, SHP-1 association and Cul4A-complex membership assertions?
Experiment: Compare equal amounts of assembled human cyclin D1βCDK4 trimers containing unmodified or site-resolved phosphorylated p27, measuring substrate-dependent kinase kinetics and docking alongside complex stability. Test the corresponding states in matched cells without treating phosphomimetic substitutions as identical to phosphorylation.
Hypothesis: p27 phosphorylation changes substrate-dependent catalytic output after complex assembly, rather than being universally required for assembly.
Type: quantitative reconstitution and cellular comparison
Experiment: In matched cell types, compare localization-controlled p27 variants while measuring RhoA-GTP, microtubule dynamics, migration and cell-cycle distribution; separate partner-interface effects from changes in p27 abundance.
Hypothesis: The balance of RhoA- and stathmin-associated interactions helps explain context-dependent cytoplasmic p27 effects.
Type: separation-of-function analysis
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