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Cyclin-dependent kinase inhibitor 1B



Mus musculus (Mouse)
Reviewed-Annotation score: -Experimental evidence at protein leveli


Important regulator of cell cycle progression (PubMed:8033213, PubMed:12972555). Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (By similarity). Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes (PubMed:8033213). 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.By similarity6 Publications


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei90Required for interaction with NUP501

GO - Molecular functioni

GO - Biological processi

  • autophagic cell death Source: MGI
  • cell cycle arrest Source: MGI
  • cellular response to antibiotic Source: MGI
  • cellular response to lithium ion Source: MGI
  • cellular response to organic cyclic compound Source: MGI
  • G1/S transition of mitotic cell cycle Source: UniProtKB
  • inner ear development Source: MGI
  • mitotic cell cycle arrest Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of cell cycle Source: MGI
  • negative regulation of cell growth Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of cellular component movement Source: MGI
  • negative regulation of cyclin-dependent protein kinase activity Source: MGI
  • negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGI
  • negative regulation of epithelial cell proliferation Source: MGI
  • negative regulation of epithelial cell proliferation involved in prostate gland development Source: MGI
  • negative regulation of kinase activity Source: MGI
  • negative regulation of mitotic cell cycle Source: MGI
  • negative regulation of phosphorylation Source: MGI
  • negative regulation of transcription, DNA-templated Source: MGI
  • negative regulation of vascular smooth muscle cell proliferation Source: MGI
  • Notch signaling pathway Source: MGI
  • placenta development Source: MGI
  • positive regulation of cell death Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: Ensembl
  • positive regulation of microtubule polymerization Source: MGI
  • positive regulation of protein catabolic process Source: Ensembl
  • potassium ion transport Source: MGI
  • regulation of exit from mitosis Source: MGI
  • regulation of lens fiber cell differentiation Source: MGI
  • response to amino acid Source: Ensembl
  • response to cadmium ion Source: Ensembl
  • response to drug Source: Ensembl
  • response to estradiol Source: Ensembl
  • response to glucose Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to peptide hormone Source: Ensembl
  • sensory perception of sound Source: MGI


Molecular functionProtein kinase inhibitor
Biological processCell cycle

Enzyme and pathway databases

ReactomeiR-MMU-176408 Regulation of APC/C activators between G1/S and early anaphase
R-MMU-187577 SCF(Skp2)-mediated degradation of p27/p21
R-MMU-198323 AKT phosphorylates targets in the cytosol
R-MMU-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-MMU-2559586 DNA Damage/Telomere Stress Induced Senescence
R-MMU-6804116 TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
R-MMU-69202 Cyclin E associated events during G1/S transition
R-MMU-69231 Cyclin D associated events in G1
R-MMU-69563 p53-Dependent G1 DNA Damage Response
R-MMU-69656 Cyclin A:Cdk2-associated events at S phase entry
R-MMU-8849470 PTK6 Regulates Cell Cycle

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase inhibitor 1B
Alternative name(s):
Cyclin-dependent kinase inhibitor p271 Publication
p27Kip11 Publication
Gene namesi
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:104565 Cdkn1b

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Nucleus

Pathology & Biotechi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10S → A: Loss of phosphorylation in G(0) phase. No change in cMYC-induced CDK2-mediated phosphorylation. Rapid dissociation from the cyclin E/CDK2 complex after induction by cMYC. Loss of protein stability in G(0) phase. No change in protein stability at S-phase. 2 Publications1
Mutagenesisi90R → G: Loss of interaction with NUP50. No cyclin E-mediated degradation of phosphorylated p27KIP1. 1 Publication1
Mutagenesisi187T → E: Loss of cMyc-induced CDK2-mediated phosphorylation. Rapid dissociation from the cyclin E/CDK2 complex after induction by c-Myc. 1 Publication1
Mutagenesisi187T → V: Loss of cMYC-induced CDK2-mediated phosphorylation Dissociates very slowly from the cyclin E/CDK2 complex after induction by cMYC. Cell cycle arrest. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001900851 – 197Cyclin-dependent kinase inhibitor 1BAdd BLAST197

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10Phosphoserine; by UHMK1Combined sources2 Publications1
Modified residuei74Phosphotyrosine; by SRCBy similarity1
Modified residuei88Phosphotyrosine; by ABL, LYN, SRC and JAK2By similarity1
Modified residuei89PhosphotyrosineBy similarity1
Modified residuei170Phosphothreonine; by CaMK11 Publication1
Modified residuei187Phosphothreonine; by PKB/AKT1, CDK1 and CDK21 Publication1
Modified residuei197Phosphothreonine; by CaMK1, PKB/AKT1, RPS6KA1, RPS6KA3 and PIM1By similarity1

Post-translational modificationi

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 G0-G1 phase and leads to protein stability. Phosphorylation on other sites is greatly enhanced by mitogens, growth factors, MYC and in certain cancer cell lines. The phosphorylated form found in the cytoplasm is inactivate. Phosphorylation on Thr-197 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 (By similarity). Dephosphorylated on Thr-187 by PPM1H, leading to CDKN1B stability (By similarity).By similarity
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 (By similarity).By similarity
Subject to degradation in the lysosome. Interaction with SNX6 promotes lysosomal degradation.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases


PTM databases



Gene expression databases

GenevisibleiP46414 MM


Subunit structurei

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-197-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. Interacts with AKT1 and LYN; the interactions lead to cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of cell cycle arrest. 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. 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. Interacts with PIM1. Identified in a complex with SKP1, SKP2 and CKS1B. Interacts with UHMK1; the interaction leads to cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of cell cycle arrest. Interacts also with CDK1. Dephosphorylated on Thr-187 by PPM1H, leading to CDKN1B stability (By similarity).By similarity8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198652, 23 interactors
IntActiP46414, 9 interactors


3D structure databases


Family & Domainsi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni51 – 91Interaction with CDK2By similarityAdd BLAST41


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi153 – 169Nuclear localization signalSequence analysisAdd BLAST17


A peptide sequence containing only AA 28-79 retains substantial Kip1 cyclin A/CDK2 inhibitory activity.By similarity

Sequence similaritiesi

Belongs to the CDI family.Curated

Phylogenomic databases

eggNOGiKOG4743 Eukaryota

Family and domain databases

InterProiView protein in InterPro
IPR003175 CDI
IPR029843 CDKN1B
PANTHERiPTHR10265 PTHR10265, 1 hit
PTHR10265:SF9 PTHR10265:SF9, 1 hit
PfamiView protein in Pfam
PF02234 CDI, 1 hit


Sequence statusi: Complete.

P46414-1 [UniParc]FASTAAdd to basket

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        10         20         30         40         50
60 70 80 90 100
110 120 130 140 150
160 170 180 190
Mass (Da):22,193
Last modified:October 3, 2012 - v2

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti22E → D in AAA21149 (PubMed:8033213).Curated1
Sequence conflicti22E → D in AAA20235 (PubMed:8033212).Curated1
Sequence conflicti22E → D in AAH14296 (PubMed:15489334).Curated1
Sequence conflicti141P → Q in AAA21149 (PubMed:8033213).Curated1
Sequence conflicti141P → Q in AAA20235 (PubMed:8033212).Curated1
Sequence conflicti141P → Q in AAH14296 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
Links Updated
U10440 mRNA Translation: AAA21149.1
U09968 mRNA Translation: AAA20235.1
AK046676 mRNA Translation: BAC32833.1
AK047669 mRNA Translation: BAC33119.1
AK050240 mRNA Translation: BAC34141.1
AC122193 Genomic DNA No translation available.
BC014296 mRNA Translation: AAH14296.1
RefSeqiNP_034005.2, NM_009875.4

Genome annotation databases

EnsembliENSMUST00000003115; ENSMUSP00000003115; ENSMUSG00000003031
ENSMUST00000067327; ENSMUSP00000065832; ENSMUSG00000003031
ENSMUST00000204807; ENSMUSP00000145056; ENSMUSG00000003031
UCSCiuc009ela.2 mouse

Similar proteinsi

Entry informationi

Entry nameiCDN1B_MOUSE
AccessioniPrimary (citable) accession number: P46414
Secondary accession number(s): Q8BG74
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 3, 2012
Last modified: May 23, 2018
This is version 153 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

Complete proteome, Reference proteome


  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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