UniProtKB - P39689 (CDN1A_MOUSE)
Cyclin-dependent kinase inhibitor 1
Cdkn1a
Functioni
May be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex (PubMed:25329316).
Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (By similarity).
Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (By similarity).
By similarity1 PublicationRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 12 – 40 | C4-typeSequence analysisAdd BLAST | 29 |
GO - Molecular functioni
- cyclin binding Source: BHF-UCL
- cyclin-dependent protein kinase activating kinase activity Source: MGI
- cyclin-dependent protein serine/threonine kinase inhibitor activity Source: MGI
- metal ion binding Source: UniProtKB-KW
- protein-containing complex binding Source: MGI
- protein kinase binding Source: MGI
- protein kinase inhibitor activity Source: MGI
- protein sequestering activity Source: MGI
- ubiquitin protein ligase binding Source: MGI
GO - Biological processi
- cellular response to amino acid starvation Source: UniProtKB
- cellular response to DNA damage stimulus Source: MGI
- cellular response to extracellular stimulus Source: MGI
- cellular response to gamma radiation Source: MGI
- cellular response to ionizing radiation Source: MGI
- cellular response to UV-B Source: UniProtKB
- cellular senescence Source: MGI
- DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: MGI
- DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: MGI
- heart development Source: BHF-UCL
- intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: MGI
- mitotic G2 DNA damage checkpoint signaling Source: UniProtKB
- negative regulation of apoptotic process Source: MGI
- negative regulation of cardiac muscle tissue regeneration Source: BHF-UCL
- negative regulation of cell growth Source: MGI
- negative regulation of cell population proliferation 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 DNA biosynthetic process Source: MGI
- negative regulation of G1/S transition of mitotic cell cycle Source: MGI
- negative regulation of gene expression Source: MGI
- negative regulation of phosphorylation Source: MGI
- negative regulation of protein binding Source: MGI
- negative regulation of vascular associated smooth muscle cell proliferation Source: MGI
- positive regulation of B cell proliferation Source: MGI
- positive regulation of cell death Source: MGI
- positive regulation of fibroblast proliferation Source: MGI
- positive regulation of programmed cell death Source: MGI
- positive regulation of protein kinase activity Source: MGI
- positive regulation of reactive oxygen species metabolic process Source: MGI
- protein import into nucleus Source: MGI
- Ras protein signal transduction Source: Ensembl
- regulation of cell cycle Source: MGI
- regulation of cell cycle G1/S phase transition Source: UniProtKB
- regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGI
- regulation of DNA biosynthetic process Source: MGI
- regulation of G1/S transition of mitotic cell cycle Source: MGI
- regulation of G2/M transition of mitotic cell cycle Source: MGI
- regulation of mitotic cell cycle Source: MGI
- response to UV Source: MGI
- tissue regeneration Source: BHF-UCL
- wound healing Source: BHF-UCL
Keywordsi
Molecular function | Protein kinase inhibitor |
Biological process | Cell cycle |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | 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-8852276, The role of GTSE1 in G2/M progression after G2 checkpoint R-MMU-9616222, Transcriptional regulation of granulopoiesis |
Names & Taxonomyi
Protein namesi | Recommended name: Cyclin-dependent kinase inhibitor 1Alternative name(s): CDK-interacting protein 1 Melanoma differentiation-associated protein p21 |
Gene namesi | Name:Cdkn1a Synonyms:Cip1, Waf1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:104556, Cdkn1a |
VEuPathDBi | HostDB:ENSMUSG00000023067 |
Subcellular locationi
Cytosol
- cytosol Source: MGI
Nucleus
- nuclear body Source: MGI
- nucleolus Source: MGI
- nucleoplasm Source: MGI
- nucleus Source: MGI
- PCNA-p21 complex Source: UniProtKB
Other locations
- cyclin-dependent protein kinase holoenzyme complex Source: MGI
- cytoplasm Source: MGI
- perinuclear region of cytoplasm Source: MGI
- protein-containing complex Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000190080 | 2 – 159 | Cyclin-dependent kinase inhibitor 1Add BLAST | 158 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserineBy similarity | 1 | |
Cross-linki | 2 | Glycyl serine ester (Ser-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 78 | Phosphoserine; by NUAK11 Publication | 1 | |
Modified residuei | 112 | Phosphoserine; by GSK3-betaBy similarity | 1 | |
Modified residuei | 125 | PhosphoserineBy similarity | 1 | |
Modified residuei | 140 | Phosphothreonine; by PKA, PKB/AKT1, PIM1 and PIM2By similarity | 1 | |
Modified residuei | 141 | Phosphoserine; by NUAK11 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P39689 |
PaxDbi | P39689 |
PeptideAtlasi | P39689 |
PRIDEi | P39689 |
ProteomicsDBi | 281569 |
PTM databases
iPTMneti | P39689 |
PhosphoSitePlusi | P39689 |
Expressioni
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000023067, Expressed in stroma of bone marrow and 337 other tissues |
ExpressionAtlasi | P39689, baseline and differential |
Genevisiblei | P39689, MM |
Interactioni
Subunit structurei
Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21 (PubMed:20154723).
Interacts with MKRN1.
Interacts with PSMA3.
Interacts with PCNA.
Component of the ternary complex, cyclin D-CDK4-CDKN1A.
Interacts (via its N-terminal domain) with CDK4; the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Binding to CDK2 leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair.
Interacts with PIM1 (By similarity).
Interacts with STK11 (PubMed:25329316).
Interacts with NUAK1 (By similarity).
Interacts with DTL and TRIM39 (By similarity).
By similarity2 PublicationsBinary interactionsi
GO - Molecular functioni
- cyclin binding Source: BHF-UCL
- protein kinase binding Source: MGI
- ubiquitin protein ligase binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 198651, 15 interactors |
CORUMi | P39689 |
DIPi | DIP-24178N |
ELMi | P39689 |
IntActi | P39689, 4 interactors |
MINTi | P39689 |
STRINGi | 10090.ENSMUSP00000023829 |
Miscellaneous databases
RNActi | P39689, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 17 – 24 | Required for binding cyclinsBy similarity | 8 | |
Regioni | 53 – 58 | Required for binding CDKsBy similarity | 6 | |
Regioni | 78 – 106 | DisorderedSequence analysisAdd BLAST | 29 | |
Regioni | 118 – 142 | DisorderedSequence analysisAdd BLAST | 25 | |
Regioni | 147 – 159 | Interaction with TRIM39By similarityAdd BLAST | 13 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 135 – 159 | PIP-box K+4 motifAdd BLAST | 25 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 12 – 40 | C4-typeSequence analysisAdd BLAST | 29 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG4743, Eukaryota |
GeneTreei | ENSGT00940000159918 |
HOGENOMi | CLU_077692_1_1_1 |
InParanoidi | P39689 |
OMAi | KVCRRLF |
OrthoDBi | 1595421at2759 |
PhylomeDBi | P39689 |
TreeFami | TF101038 |
Family and domain databases
Gene3Di | 4.10.365.10, 1 hit |
InterProi | View protein in InterPro IPR003175, CDI_dom IPR044898, CDI_dom_sf IPR029841, CDKN1A |
PANTHERi | PTHR46778, PTHR46778, 1 hit |
Pfami | View protein in Pfam PF02234, CDI, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MSNPGDVRPV PHRSKVCRCL FGPVDSEQLR RDCDALMAGC LQEARERWNF
60 70 80 90 100
DFVTETPLEG NFVWERVRSL GLPKVYLSPG SRSRDDLGGD KRPSTSSALL
110 120 130 140 150
QGPAPEDHVA LSLSCTLVSE RPEDSPGGPG TSQGRKRRQT SLTDFYHSKR
RLVFCKRKP
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 30 | R → S no nucleotide entry (PubMed:8242752).Curated | 1 | |
Sequence conflicti | 56 – 57 | TP → RQ no nucleotide entry (PubMed:8242752).Curated | 2 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U09507 mRNA Translation: AAB60456.1 U24173 mRNA Translation: AAC52220.1 BC002043 mRNA Translation: AAH02043.1 |
CCDSi | CCDS28591.1 |
PIRi | A49438 I49023 |
RefSeqi | NP_001104569.1, NM_001111099.2 NP_031695.1, NM_007669.5 |
Genome annotation databases
Ensembli | ENSMUST00000023829; ENSMUSP00000023829; ENSMUSG00000023067 ENSMUST00000119901; ENSMUSP00000113150; ENSMUSG00000023067 ENSMUST00000122348; ENSMUSP00000112411; ENSMUSG00000023067 ENSMUST00000233296; ENSMUSP00000156559; ENSMUSG00000023067 |
GeneIDi | 12575 |
KEGGi | mmu:12575 |
UCSCi | uc008bsg.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U09507 mRNA Translation: AAB60456.1 U24173 mRNA Translation: AAC52220.1 BC002043 mRNA Translation: AAH02043.1 |
CCDSi | CCDS28591.1 |
PIRi | A49438 I49023 |
RefSeqi | NP_001104569.1, NM_001111099.2 NP_031695.1, NM_007669.5 |
3D structure databases
AlphaFoldDBi | P39689 |
SMRi | P39689 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 198651, 15 interactors |
CORUMi | P39689 |
DIPi | DIP-24178N |
ELMi | P39689 |
IntActi | P39689, 4 interactors |
MINTi | P39689 |
STRINGi | 10090.ENSMUSP00000023829 |
PTM databases
iPTMneti | P39689 |
PhosphoSitePlusi | P39689 |
Proteomic databases
EPDi | P39689 |
PaxDbi | P39689 |
PeptideAtlasi | P39689 |
PRIDEi | P39689 |
ProteomicsDBi | 281569 |
Protocols and materials databases
Antibodypediai | 3757, 2430 antibodies from 47 providers |
DNASUi | 12575 |
Genome annotation databases
Organism-specific databases
CTDi | 1026 |
MGIi | MGI:104556, Cdkn1a |
VEuPathDBi | HostDB:ENSMUSG00000023067 |
Phylogenomic databases
eggNOGi | KOG4743, Eukaryota |
GeneTreei | ENSGT00940000159918 |
HOGENOMi | CLU_077692_1_1_1 |
InParanoidi | P39689 |
OMAi | KVCRRLF |
OrthoDBi | 1595421at2759 |
PhylomeDBi | P39689 |
TreeFami | TF101038 |
Enzyme and pathway databases
Reactomei | 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-8852276, The role of GTSE1 in G2/M progression after G2 checkpoint R-MMU-9616222, Transcriptional regulation of granulopoiesis |
Miscellaneous databases
BioGRID-ORCSi | 12575, 9 hits in 78 CRISPR screens |
ChiTaRSi | Cdkn1a, mouse |
PROi | PR:P39689 |
RNActi | P39689, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000023067, Expressed in stroma of bone marrow and 337 other tissues |
ExpressionAtlasi | P39689, baseline and differential |
Genevisiblei | P39689, MM |
Family and domain databases
Gene3Di | 4.10.365.10, 1 hit |
InterProi | View protein in InterPro IPR003175, CDI_dom IPR044898, CDI_dom_sf IPR029841, CDKN1A |
PANTHERi | PTHR46778, PTHR46778, 1 hit |
Pfami | View protein in Pfam PF02234, CDI, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CDN1A_MOUSE | |
Accessioni | P39689Primary (citable) accession number: P39689 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 179 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families