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Protein

Cyclin-dependent kinase inhibitor 1B

Gene

Cdkn1b

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

Functioni

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

Sites

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

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
Name:Cdkn1b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • 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

Mutagenesis

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

EPDiP46414
PaxDbiP46414
PeptideAtlasiP46414
PRIDEiP46414

PTM databases

iPTMnetiP46414
PhosphoSitePlusiP46414

Expressioni

Gene expression databases

BgeeiENSMUSG00000003031 Expressed in 292 organ(s), highest expression level in cerebellar vermis
CleanExiMM_CDKN1B
GenevisibleiP46414 MM

Interactioni

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198652, 23 interactors
DIPiDIP-445N
IntActiP46414, 9 interactors
MINTiP46414
STRINGi10090.ENSMUSP00000003115

Structurei

3D structure databases

ProteinModelPortaliP46414
SMRiP46414
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

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

Motif

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

Domaini

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
ENOG410XXN5 LUCA
GeneTreeiENSGT00530000063588
HOGENOMiHOG000294081
HOVERGENiHBG073988
InParanoidiP46414
KOiK06624
OMAiYPKPSAC
OrthoDBiEOG091G19PZ
TreeFamiTF101038

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

Sequencei

Sequence statusi: Complete.

P46414-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSNVRVSNGS PSLERMDARQ AEHPKPSACR NLFGPVNHEE LTRDLEKHCR
60 70 80 90 100
DMEEASQRKW NFDFQNHKPL EGRYEWQEVE RGSLPEFYYR PPRPPKSACK
110 120 130 140 150
VLAQESQDVS GSRQAVPLIG SQANSEDRHL VDQMPDSSDN PAGLAEQCPG
160 170 180 190
MRKRPAAEDS SSQNKRANRT EENVSDGSPN AGTVEQTPKK PGLRRQT
Length:197
Mass (Da):22,193
Last modified:October 3, 2012 - v2
Checksum:iBAC30D648B9BA3D6
GO

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:
EMBLi
GenBanki
DDBJi
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
CCDSiCCDS20642.1
PIRiI49064
RefSeqiNP_034005.2, NM_009875.4
UniGeneiMm.2958

Genome annotation databases

EnsembliENSMUST00000003115; ENSMUSP00000003115; ENSMUSG00000003031
ENSMUST00000067327; ENSMUSP00000065832; ENSMUSG00000003031
ENSMUST00000204807; ENSMUSP00000145056; ENSMUSG00000003031
GeneIDi12576
KEGGimmu:12576
UCSCiuc009ela.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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
CCDSiCCDS20642.1
PIRiI49064
RefSeqiNP_034005.2, NM_009875.4
UniGeneiMm.2958

3D structure databases

ProteinModelPortaliP46414
SMRiP46414
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198652, 23 interactors
DIPiDIP-445N
IntActiP46414, 9 interactors
MINTiP46414
STRINGi10090.ENSMUSP00000003115

PTM databases

iPTMnetiP46414
PhosphoSitePlusiP46414

Proteomic databases

EPDiP46414
PaxDbiP46414
PeptideAtlasiP46414
PRIDEiP46414

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000003115; ENSMUSP00000003115; ENSMUSG00000003031
ENSMUST00000067327; ENSMUSP00000065832; ENSMUSG00000003031
ENSMUST00000204807; ENSMUSP00000145056; ENSMUSG00000003031
GeneIDi12576
KEGGimmu:12576
UCSCiuc009ela.2 mouse

Organism-specific databases

CTDi1027
MGIiMGI:104565 Cdkn1b

Phylogenomic databases

eggNOGiKOG4743 Eukaryota
ENOG410XXN5 LUCA
GeneTreeiENSGT00530000063588
HOGENOMiHOG000294081
HOVERGENiHBG073988
InParanoidiP46414
KOiK06624
OMAiYPKPSAC
OrthoDBiEOG091G19PZ
TreeFamiTF101038

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

Miscellaneous databases

ChiTaRSiCdkn1b mouse
PROiPR:P46414
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003031 Expressed in 292 organ(s), highest expression level in cerebellar vermis
CleanExiMM_CDKN1B
GenevisibleiP46414 MM

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
ProtoNetiSearch...

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: November 7, 2018
This is version 156 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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