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Details on Person UniProt:P46527 CDKN1B

Class:Id	ReferenceGeneProduct:198633
_chainChangeLog	chain:1-198 added on Fri February 6 2015
_displayName	UniProt:P46527 CDKN1B
_timestamp	2025-05-21 21:35:34
chain	chain:1-198
checksum	1118D58901CDF3FC
comment	FUNCTION Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995). Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.SUBUNIT Forms a ternary complex composed of CCNE1, CDK2 and CDKN1B. Interacts directly with CCNE1; the interaction is inhibited by CDK2-dependent phosphorylation on Thr-187. Interacts with COPS5, subunit of the COP9 signalosome complex; the interaction leads to CDKN1B degradation. Interacts with NUP50; the interaction leads to nuclear import and degradation of phosphorylated CDKN1B. Interacts with CCND1 and SNX6 (By similarity). Interacts (Thr-198-phosphorylated form) with 14-3-3 proteins, binds strongly YWHAQ, weakly YWHAE and YWHAH, but not YWHAB nor YWHAZ; the interaction with YWHAQ results in translocation to the cytoplasm (PubMed:14504289). Interacts with AKT1 and LYN; the interactions lead to cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of cell cycle arrest (PubMed:12042314, PubMed:12244301, PubMed:17254966). Forms a ternary complex with CCNA2 and CDK2; CDKN1B inhibits the kinase activity of CDK2 through conformational rearrangements. Interacts (unphosphorylated form) with CDK2. Forms a complex with CDK2 and SPDYA, but does not directly interact with SPDYA (PubMed:12972555, PubMed:28666995). Forms a ternary complex composed of cyclin D, CDK4 and CDKN1B. Interacts (phosphorylated on Tyr-88 and Tyr-89) with CDK4; the interaction is required for cyclin D and CDK4 complex assembly, induces nuclear translocation and activates the CDK4 kinase activity. Interacts with GRB2 (PubMed:16195327). Interacts with PIM1 (PubMed:18593906). Identified in a complex with SKP1, SKP2 and CKS1B (PubMed:16209941). Interacts with UHMK1; the interaction leads to cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of cell cycle arrest (PubMed:12093740). Also interacts with CDK1 (PubMed:16007079). Dephosphorylated on Thr-187 by PPM1H, leading to CDKN1B stability (PubMed:22586611). Interacts with HSPA8; the interaction may be associated with susceptibility to ubiquitination (PubMed:26775844).INTERACTION Nuclear and cytoplasmic in quiescent cells. AKT- or RSK-mediated phosphorylation on Thr-198, binds 14-3-3, translocates to the cytoplasm and promotes cell cycle progression. Mitogen-activated UHMK1 phosphorylation on Ser-10 also results in translocation to the cytoplasm and cell cycle progression. Phosphorylation on Ser-10 facilitates nuclear export. Translocates to the nucleus on phosphorylation of Tyr-88 and Tyr-89. Colocalizes at the endosome with SNX6; this leads to lysosomal degradation (By similarity).TISSUE SPECIFICITY Expressed in kidney (at protein level) (PubMed:15509543). Expressed in all tissues tested (PubMed:8033212). Highest levels in skeletal muscle, lowest in liver and kidney (PubMed:8033212).INDUCTION Maximal levels in quiescence cells and early G(1). Levels decrease after mitogen stimulation as cells progress toward S-phase.DOMAIN A peptide sequence containing only AA 28-79 retains substantial Kip1 cyclin A/CDK2 inhibitory activity.PTM Phosphorylated; phosphorylation occurs on serine, threonine and tyrosine residues. Phosphorylation on Ser-10 is the major site of phosphorylation in resting cells, takes place at the G(0)-G(1) phase and leads to protein stability. Phosphorylation on other sites is greatly enhanced by mitogens, growth factors, cMYC and in certain cancer cell lines. The phosphorylated form found in the cytoplasm is inactivate. Phosphorylation on Thr-198 is required for interaction with 14-3-3 proteins. Phosphorylation on Thr-187, by CDK1 and CDK2 leads to protein ubiquitination and proteasomal degradation. Tyrosine phosphorylation promotes this process. Phosphorylation by PKB/AKT1 can be suppressed by LY294002, an inhibitor of the catalytic subunit of PI3K. Phosphorylation on Tyr-88 and Tyr-89 has no effect on binding CDK2, but is required for binding CDK4. Dephosphorylated on tyrosine residues by G-CSF.PTM Ubiquitinated; in the cytoplasm by the KPC complex (composed of RNF123/KPC1 and UBAC1/KPC2) and, in the nucleus, by SCF(SKP2). The latter requires prior phosphorylation on Thr-187. Ubiquitinated; by a TRIM21-containing SCF(SKP2)-like complex; leads to its degradation.PTM Subject to degradation in the lysosome. Interaction with SNX6 promotes lysosomal degradation (By similarity).DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Decreased levels of p27Kip1, mainly due to proteasomal degradation, are found in various epithelial tumors originating from lung, breast, colon, ovary, esophagus, thyroid and prostate.SIMILARITY Belongs to the CDI family.
created	[InstanceEdit:198616] Jassal, B, 2007-06-29 07:57:48
description	recommendedName: Cyclin-dependent kinase inhibitor 1B alternativeName: fullName evidence="40"Cyclin-dependent kinase inhibitor p27 alternativeName: fullName evidence="41"p27Kip1
geneName	CDKN1B KIP1 p27
identifier	P46527
isSequenceChanged	FALSE
keyword	3D-structure Cell cycle Cytoplasm Direct protein sequencing Endosome Nucleus Phosphoprotein Protein kinase inhibitor Proteomics identification Reference proteome Tumor suppressor Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21
name	CDKN1B
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8992350] ENSEMBL:ENSG00000111276 CDKN1B [Homo sapiens]
secondaryIdentifier	CDN1B_HUMAN Q16307 Q5U0H2 Q9BUS6
sequenceLength	198
species	[Species:48887] Homo sapiens
(referenceEntity)	[EntityWithAccessionedSequence:182563] CDKN1B [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:187525] p-T187-CDKN1B [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:198622] CDKN1B [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:198629] p-T157-CDKN1B [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:8848438] p-Y88-CDKN1B [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:8848471] p-Y88,T187-CDKN1B [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:8848488] p-Y88,T187-CDKN1B [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:8942808] p-Y88-CDKN1B [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9632829] p-S10 CDKN1B [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9632832] p-S10 CDKN1B [nucleoplasm] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:187514] O-phospho-L-threonine at 187 [ModifiedResidue:198645] O-phospho-L-threonine at 157 [ModifiedResidue:8848439] O4'-phospho-L-tyrosine at 88 [ModifiedResidue:9632828] O-phospho-L-serine at 10
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