P46414 · CDN1B_MOUSE
- ProteinCyclin-dependent kinase inhibitor 1B
- GeneCdkn1b
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids197 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Important regulator of cell cycle progression (PubMed:12972555, PubMed:8033213).
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
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
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 90 | Required for interaction with NUP50 | ||||
Sequence: R |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCyclin-dependent kinase inhibitor 1B
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP46414
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Nuclear and cytoplasmic in quiescent cells. AKT- or RSK-mediated phosphorylation on Thr-197, 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 (By similarity).
Colocalizes at the endosome with SNX6; this leads to lysosomal degradation (PubMed:20228253).
Colocalizes at the endosome with SNX6; this leads to lysosomal degradation (PubMed:20228253).
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 10 | Loss of phosphorylation in G0 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 G0 phase. No change in protein stability at S-phase. | ||||
Sequence: S → A | ||||||
Mutagenesis | 90 | Loss of interaction with NUP50. No cyclin E-mediated degradation of phosphorylated p27KIP1. | ||||
Sequence: R → G | ||||||
Mutagenesis | 187 | Loss of cMyc-induced CDK2-mediated phosphorylation. Rapid dissociation from the cyclin E/CDK2 complex after induction by c-Myc. | ||||
Sequence: T → E | ||||||
Mutagenesis | 187 | Loss of cMYC-induced CDK2-mediated phosphorylation Dissociates very slowly from the cyclin E/CDK2 complex after induction by cMYC. Cell cycle arrest. | ||||
Sequence: T → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 4 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000190085 | 1-197 | Cyclin-dependent kinase inhibitor 1B | |||
Sequence: MSNVRVSNGSPSLERMDARQAEHPKPSACRNLFGPVNHEELTRDLEKHCRDMEEASQRKWNFDFQNHKPLEGRYEWQEVERGSLPEFYYRPPRPPKSACKVLAQESQDVSGSRQAVPLIGSQANSEDRHLVDQMPDSSDNPAGLAEQCPGMRKRPAAEDSSSQNKRANRTEENVSDGSPNAGTVEQTPKKPGLRRQT | ||||||
Modified residue | 10 | Phosphoserine; by UHMK1 | ||||
Sequence: S | ||||||
Modified residue | 74 | Phosphotyrosine; by SRC | ||||
Sequence: Y | ||||||
Modified residue | 88 | Phosphotyrosine; by ABL, LYN, SRC and JAK2 | ||||
Sequence: Y | ||||||
Modified residue | 89 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 170 | Phosphothreonine; by CaMK1 | ||||
Sequence: T | ||||||
Modified residue | 187 | Phosphothreonine; by PKB/AKT1, CDK1 and CDK2 | ||||
Sequence: T | ||||||
Modified residue | 197 | Phosphothreonine; by CaMK1, PKB/AKT1, RPS6KA1, RPS6KA3 and PIM1 | ||||
Sequence: T |
Post-translational modification
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).
Dephosphorylated on Thr-187 by PPM1H, leading to CDKN1B stability (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).
Subject to degradation in the lysosome. Interaction with SNX6 promotes lysosomal degradation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
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-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).
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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P46414 | Cdk4 P30285 | 2 | EBI-1005742, EBI-847225 | |
BINARY | P46414 | Mcm7 Q61881 | 2 | EBI-1005742, EBI-457180 | |
BINARY | P46414 | Stmn1 P54227 | 2 | EBI-1005742, EBI-1006438 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-34 | Disordered | ||||
Sequence: MSNVRVSNGSPSLERMDARQAEHPKPSACRNLFG | ||||||
Region | 51-91 | Interaction with CDK2 | ||||
Sequence: DMEEASQRKWNFDFQNHKPLEGRYEWQEVERGSLPEFYYRP | ||||||
Region | 86-197 | Disordered | ||||
Sequence: EFYYRPPRPPKSACKVLAQESQDVSGSRQAVPLIGSQANSEDRHLVDQMPDSSDNPAGLAEQCPGMRKRPAAEDSSSQNKRANRTEENVSDGSPNAGTVEQTPKKPGLRRQT | ||||||
Compositional bias | 103-121 | Polar residues | ||||
Sequence: AQESQDVSGSRQAVPLIGS | ||||||
Motif | 153-169 | Nuclear localization signal | ||||
Sequence: KRPAAEDSSSQNKRANR | ||||||
Compositional bias | 158-172 | Basic and acidic residues | ||||
Sequence: EDSSSQNKRANRTEE |
Domain
A peptide sequence containing only AA 28-79 retains substantial Kip1 cyclin A/CDK2 inhibitory activity.
Sequence similarities
Belongs to the CDI family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length197
- Mass (Da)22,193
- Last updated2012-10-03 v2
- ChecksumBAC30D648B9BA3D6
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 22 | in Ref. 1; AAA21149, 2; AAA20235 and 5; AAH14296 | ||||
Sequence: E → D | ||||||
Compositional bias | 103-121 | Polar residues | ||||
Sequence: AQESQDVSGSRQAVPLIGS | ||||||
Sequence conflict | 141 | in Ref. 1; AAA21149, 2; AAA20235 and 5; AAH14296 | ||||
Sequence: P → Q | ||||||
Compositional bias | 158-172 | Basic and acidic residues | ||||
Sequence: EDSSSQNKRANRTEE |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U10440 EMBL· GenBank· DDBJ | AAA21149.1 EMBL· GenBank· DDBJ | mRNA | ||
U09968 EMBL· GenBank· DDBJ | AAA20235.1 EMBL· GenBank· DDBJ | mRNA | ||
AK046676 EMBL· GenBank· DDBJ | BAC32833.1 EMBL· GenBank· DDBJ | mRNA | ||
AK047669 EMBL· GenBank· DDBJ | BAC33119.1 EMBL· GenBank· DDBJ | mRNA | ||
AK050240 EMBL· GenBank· DDBJ | BAC34141.1 EMBL· GenBank· DDBJ | mRNA | ||
AC122193 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC014296 EMBL· GenBank· DDBJ | AAH14296.1 EMBL· GenBank· DDBJ | mRNA |