This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediate... See more...

Aliases for CDKN1A Gene

Aliases for CDKN1A Gene

  • Cyclin Dependent Kinase Inhibitor 1A 2 3 5
  • P21 2 2 3 4
  • CAP20 2 3 4
  • CIP1 2 3 4
  • SDI1 2 3 4
  • WAF1 2 3 4
  • Cyclin-Dependent Kinase Inhibitor 1A (P21, Cip1) 2 3
  • Cyclin-Dependent Kinase Inhibitor 1 3 4
  • CDK-Interacting Protein 1 3 4
  • P21CIP1 2 3
  • CDKN1 3 4
  • MDA-6 3 4
  • Melanoma Differentiation Associated Protein 6 3
  • Melanoma Differentiation-Associated Protein 6 4
  • Wild-Type P53-Activated Fragment 1 3
  • CDK-Interaction Protein 1 3
  • DNA Synthesis Inhibitor 3
  • P21Cip1/Waf1 2
  • CDKN1A 5
  • MDA6 4
  • PIC1 4

External Ids for CDKN1A Gene

Previous HGNC Symbols for CDKN1A Gene

  • CDKN1

Previous GeneCards Identifiers for CDKN1A Gene

  • GC06P036648
  • GC06P036693
  • GC06P036754
  • GC06P036645
  • GC06P036364
  • GC06P036649
  • GC06P036761
  • GC06P037308
  • GC06P036956
  • GC06P036998
  • GC06P042825
  • GC06P043169
  • GC06P043367
  • GC06P046057
  • GC06P037793
  • GC06P038416
  • GC06P039006
  • GC06P039594
  • GC06P040154
  • GC06P041233
  • GC06P041912
  • GC06P042554

Summaries for CDKN1A Gene

Entrez Gene Summary for CDKN1A Gene

  • This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]

CIViC Summary for CDKN1A Gene

GeneCards Summary for CDKN1A Gene

CDKN1A (Cyclin Dependent Kinase Inhibitor 1A) is a Protein Coding gene. Diseases associated with CDKN1A include Multiple Endocrine Neoplasia, Type I and Tongue Carcinoma. Among its related pathways are Apoptosis Modulation and Signaling and ATM Pathway. Gene Ontology (GO) annotations related to this gene include ubiquitin protein ligase binding and cyclin binding. An important paralog of this gene is CDKN1C.

UniProtKB/Swiss-Prot Summary for CDKN1A Gene

  • 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. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657).

Gene Wiki entry for CDKN1A Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CDKN1A Gene

Genomics for CDKN1A Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CDKN1A Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CDKN1A on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CDKN1A

Top Transcription factor binding sites by QIAGEN in the CDKN1A gene promoter:
  • MyoD

Genomic Locations for CDKN1A Gene

Genomic Locations for CDKN1A Gene
chr6:36,676,460-36,687,337
(GRCh38/hg38)
Size:
10,878 bases
Orientation:
Plus strand
chr6:36,644,237-36,655,116
(GRCh37/hg19)
Size:
10,880 bases
Orientation:
Plus strand

Genomic View for CDKN1A Gene

Genes around CDKN1A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CDKN1A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CDKN1A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CDKN1A Gene

Proteins for CDKN1A Gene

  • Protein details for CDKN1A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P38936-CDN1A_HUMAN
    Recommended name:
    Cyclin-dependent kinase inhibitor 1
    Protein Accession:
    P38936
    Secondary Accessions:
    • Q14010
    • Q6FI05
    • Q9BUT4

    Protein attributes for CDKN1A Gene

    Size:
    164 amino acids
    Molecular mass:
    18119 Da
    Quaternary structure:
    • Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21 (By similarity). Interacts with MKRN1 (PubMed:19536131). Interacts with PSMA3 (PubMed:11350925). Interacts with PCNA (PubMed:11595739, PubMed:18794347, PubMed:18703516, PubMed:8861913). 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 (PubMed:9106657). 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 (PubMed:19445729). Interacts with PIM1 (PubMed:12431783). Interacts with STK11 and NUAK1 (PubMed:25329316). Interacts wih DTL (PubMed:23213251). Interacts with isoform 1 and isoform 2 of TRIM39 (PubMed:23213251).
    SequenceCaution:
    • Sequence=AAB59559.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAB59560.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CDKN1A Gene

neXtProt entry for CDKN1A Gene

Post-translational modifications for CDKN1A Gene

  • Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs binding to PCNA. Phosphorylation at Ser-114 by GSK3-beta enhances ubiquitination by the DCX(DTL) complex. Phosphorylation of Thr-145 by PIM2 enhances CDKN1A stability and inhibits cell proliferation. Phosphorylation of Thr-145 by PIM1 results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. UV radiation-induced phosphorylation at Thr-80 by LKB1 and at Ser-146 by NUAK1 leads to its degradation.
  • Ubiquitinated by MKRN1; leading to polyubiquitination and 26S proteasome-dependent degradation. Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, leading to its degradation during S phase or following UV irradiation. Ubiquitination by the DCX(DTL) complex is essential to control replication licensing and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. Ubiquitination at Ser-2 leads to degradation by the proteasome pathway. Ubiquitinated by RNF114; leading to proteasomal degradation.
  • Acetylation leads to protein stability. Acetylated in vitro on Lys-141, Lys-154, Lys-161 and Lys-163. Deacetylation by HDAC1 is prevented by competitive binding of C10orf90/FATS to HDAC1 (By similarity).
  • Ubiquitination at Lys75
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Abcam antibodies for CDKN1A

No data available for DME Specific Peptides for CDKN1A Gene

Domains & Families for CDKN1A Gene

Gene Families for CDKN1A Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted intracellular proteins

Protein Domains for CDKN1A Gene

InterPro:
Blocks:
  • Cyclin-dependent kinase inhibitor
ProtoNet:

Suggested Antigen Peptide Sequences for CDKN1A Gene

GenScript: Design optimal peptide antigens:
  • p21 (CDN1A_HUMAN)
  • Cyclin-dependent kinase inhibitor 1A (P21, Cip1), isoform CRA_a (Q6FI05_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P38936

UniProtKB/Swiss-Prot:

CDN1A_HUMAN :
  • The PIP-box K+4 motif mediates both the interaction with PCNA and the recruitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination.
  • Belongs to the CDI family.
Domain:
  • The PIP-box K+4 motif mediates both the interaction with PCNA and the recruitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination.
  • The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex.
Family:
  • Belongs to the CDI family.
genes like me logo Genes that share domains with CDKN1A: view

Function for CDKN1A Gene

Molecular function for CDKN1A Gene

UniProtKB/Swiss-Prot Function:
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. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657).
UniProtKB/Swiss-Prot Induction:
Activated by p53/TP53, mezerein (antileukemic compound) and IFNB1. Repressed by HDAC1.
GENATLAS Biochemistry:
wild type p53-activated fragment 1,p21,regulator of cell cycle,cyclin dependent kinases 2 and 4 (CDK2/CDK4) inhibitor protein,involved in cell cycle exit in megacaryocyte,inhibiting cycle progression by interacting with G1 cyclin/CDK complexes and PCNA,this inhibitory activity antagonizing apoptosis being located in cell nucleus while,apoptosis activity located in cytoplasm,cleaved by caspase 3 in the earlier stage of apoptosis,mutated in breast carcinoma,deleted in some papillary thyroid carcinoma,hybridizing with WI-7311,WI-10190,inhibited by AMPHL in early stage of muscle differentiation program,controlling differentiation of skeletal muscle and alveoli in the lung in parallel with P21 and myogenin,also functioning as a suppressor of malignant skin tumor formation and as a determinant of keratinocyte stem-cell potential

Phenotypes From GWAS Catalog for CDKN1A Gene

Gene Ontology (GO) - Molecular Function for CDKN1A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004860 protein kinase inhibitor activity IMP 8876165
GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity TAS 7958916
GO:0005515 protein binding IPI 8756624
GO:0016301 kinase activity IEA --
GO:0019901 protein kinase binding IPI 8876165
genes like me logo Genes that share ontologies with CDKN1A: view
genes like me logo Genes that share phenotypes with CDKN1A: view

Human Phenotype Ontology for CDKN1A Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CDKN1A Gene

MGI Knock Outs for CDKN1A:

Animal Model Products

CRISPR Products

miRNA for CDKN1A Gene

miRTarBase miRNAs that target CDKN1A

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CDKN1A

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CDKN1A Gene

Localization for CDKN1A Gene

Subcellular locations from UniProtKB/Swiss-Prot for CDKN1A Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CDKN1A gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 3
extracellular 3
cytoskeleton 3
mitochondrion 3
peroxisome 2
endoplasmic reticulum 2
lysosome 2
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CDKN1A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000307 cyclin-dependent protein kinase holoenzyme complex IDA 17420273
GO:0005634 nucleus IDA 11343236
GO:0005654 nucleoplasm TAS --
GO:0005730 nucleolus IDA 22869755
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with CDKN1A: view

Pathways & Interactions for CDKN1A Gene

genes like me logo Genes that share pathways with CDKN1A: view

Pathways by source for CDKN1A Gene

15 GeneGo (Thomson Reuters) pathways for CDKN1A Gene
  • Cell cycle ESR1 regulation of G1/S transition
  • Cell cycle Regulation of G1/S transition (part 1)
  • Cell cycle Role of SCF complex in cell cycle regulation
  • Development Angiopoietin - Tie2 signaling
  • Development Role of Activin A in cell differentiation and proliferation
2 R&D Systems pathways for CDKN1A Gene
16 Qiagen pathways for CDKN1A Gene
  • Akt Signaling
  • ATM Pathway
  • Breast Cancer Regulation by Stathmin1
  • Chks in Checkpoint Regulation
  • Colorectal Cancer Metastasis
1 Cell Signaling Technology pathway for CDKN1A Gene
2 GeneTex pathways for CDKN1A Gene

Gene Ontology (GO) - Biological Process for CDKN1A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity TAS 8242751
GO:0000082 G1/S transition of mitotic cell cycle IDA,TAS --
GO:0000086 G2/M transition of mitotic cell cycle IMP 17553787
GO:0006357 regulation of transcription by RNA polymerase II TAS --
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
genes like me logo Genes that share ontologies with CDKN1A: view

Drugs & Compounds for CDKN1A Gene

(72) Drugs for CDKN1A Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Arsenic trioxide Approved, Investigational Pharma Target 131

(76) Additional Compounds for CDKN1A Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CDKN1A: view

Transcripts for CDKN1A Gene

mRNA/cDNA for CDKN1A Gene

10 REFSEQ mRNAs :
28 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products