Summary: 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].

cyclin dependent kinase inhibitor 1AMIM:116899Ensembl:ENSG00000124762HGNC:HGNC:1784PA1046p21.2

GO terms in CDKN1A

Term TypeEvidence TypeGO Term IDGO Des.
MFEXPGO:0004693cyclin-dependent protein serine/threonine kinase activity
MFIMPGO:0004860protein kinase inhibitor activity
MFTASGO:0004861cyclin-dependent protein serine/threonine kinase inhibitor activity
MFIPIGO:0005515protein binding
MFIPIGO:0019901protein kinase binding
MFIDAGO:0019912cyclin-dependent protein kinase activating kinase activity
MFIEAGO:0030332cyclin binding
MFIPIGO:0031625ubiquitin protein ligase binding
MFIPIGO:0044877protein-containing complex binding
MFIEAGO:0046872metal ion binding
BPTASGO:0000079regulation of cyclin-dependent protein serine/threonine kinase activity
BPIDAGO:0000082G1/S transition of mitotic cell cycle
BPTASGO:0000082G1/S transition of mitotic cell cycle
BPIMPGO:0000086G2/M transition of mitotic cell cycle
BPTASGO:0006357regulation of transcription by RNA polymerase II
BPTASGO:0006367transcription initiation from RNA polymerase II promoter
BPIMPGO:0006974cellular response to DNA damage stimulus
BPIDAGO:0006977DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
BPTASGO:0006977DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
BPIEAGO:0006978DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
BPIDAGO:0007050cell cycle arrest
BPIMPGO:0007050cell cycle arrest
BPIEPGO:0007265Ras protein signal transduction
BPIDAGO:0008285negative regulation of cell proliferation
BPIMPGO:0008285negative regulation of cell proliferation
BPIEAGO:0009636response to toxic substance
BPIEAGO:0010165response to X-ray
BPIEAGO:0010243response to organonitrogen compound
BPIEAGO:0010629negative regulation of gene expression
BPTASGO:0019221cytokine-mediated signaling pathway
BPIDAGO:0030308negative regulation of cell growth
BPIEAGO:0030890positive regulation of B cell proliferation
BPIEAGO:0031100animal organ regeneration
BPIMPGO:0031668cellular response to extracellular stimulus
BPIEAGO:0033158regulation of protein import into nucleus, translocation
BPIMPGO:0034198cellular response to amino acid starvation
BPIEAGO:0034605cellular response to heat
BPIDAGO:0042326negative regulation of phosphorylation
BPIEAGO:0042493response to drug
BPIEAGO:0042771intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
BPIEAGO:0043066negative regulation of apoptotic process
BPIEAGO:0043068positive regulation of programmed cell death
BPIEAGO:0045736negative regulation of cyclin-dependent protein serine/threonine kinase activity
BPIDAGO:0045860positive regulation of protein kinase activity
BPIEAGO:0046685response to arsenic-containing substance
BPIMPGO:0048146positive regulation of fibroblast proliferation
BPTASGO:0050821protein stabilization
BPIEAGO:0051412response to corticosterone
BPIEAGO:0055093response to hyperoxia
BPIEAGO:0060574intestinal epithelial cell maturation
BPIMPGO:0071479cellular response to ionizing radiation
BPIEAGO:0071480cellular response to gamma radiation
BPISSGO:0071493cellular response to UV-B
BPIEAGO:0071850mitotic cell cycle arrest
BPIMPGO:0090398cellular senescence
BPIEAGO:0090399replicative senescence
BPTASGO:0090400stress-induced premature senescence
BPTASGO:0097193intrinsic apoptotic signaling pathway
BPIMPGO:1904030negative regulation of cyclin-dependent protein kinase activity
BPIEAGO:1904031positive regulation of cyclin-dependent protein kinase activity
BPIMPGO:1904706negative regulation of vascular smooth muscle cell proliferation
BPIGIGO:2000134negative regulation of G1/S transition of mitotic cell cycle
BPIEAGO:2000278regulation of DNA biosynthetic process
BPIMPGO:2000379positive regulation of reactive oxygen species metabolic process
CCIDAGO:0000307cyclin-dependent protein kinase holoenzyme complex
CCIDAGO:0016604nuclear body
CCIDAGO:0032991protein-containing complex
CCIEAGO:0048471perinuclear region of cytoplasm
CCIDAGO:0070557PCNA-p21 complex

Gene expression in normal tissue: CDKN1A

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in CDKN1A

DatabasePathway IDPathway Des.
pidangiopoietinreceptor_pathwayAngiopoietin receptor Tie2-mediated signaling
pidcmyb_pathwayC-MYB transcription factor network
pide2f_pathwayE2F transcription factor network
pidhdac_classiii_pathwaySignaling events mediated by HDAC Class III
pidmyc_represspathwayValidated targets of C-MYC transcriptional repression
pidnotch_pathwayNotch signaling pathway
pidp53downstreampathwayDirect p53 effectors
pidp73pathwayp73 transcription factor network
pidpi3kciaktpathwayClass I PI3K signaling events mediated by Akt
pidprlsignalingeventspathwaySignaling events mediated by PRL
pidrb_1pathwayRegulation of retinoblastoma protein
pidreg_gr_pathwayGlucocorticoid receptor regulatory network
pidsmad2_3nuclearpathwayRegulation of nuclear SMAD2/3 signaling
pidtap63pathwayValidated transcriptional targets of TAp63 isoforms
pharmgkbPA152241951Celecoxib Pathway, Pharmacodynamics
smpdbSMP00436Vinblastine Action Pathway
smpdbSMP00437Vincristine Action Pathway
smpdbSMP00438Vindesine Action Pathway
smpdbSMP00439Vinorelbine Action Pathway
wikipathwaysWP138Androgen receptor signaling pathway
wikipathwaysWP1403AMP-activated Protein Kinase (AMPK) Signaling
wikipathwaysWP1530miRNA Regulation of DNA Damage Response
wikipathwaysWP1545miRNAs involved in DNA damage response
wikipathwaysWP1742TP53 Network
wikipathwaysWP1775Cell Cycle Checkpoints
wikipathwaysWP179Cell Cycle
wikipathwaysWP1971Integrated Cancer Pathway
wikipathwaysWP2004miR-targeted genes in lymphocytes - TarBase
wikipathwaysWP2005miR-targeted genes in muscle cell - TarBase
wikipathwaysWP2261Signaling Pathways in Glioblastoma
wikipathwaysWP2446Retinoblastoma (RB) in Cancer
wikipathwaysWP2516ATM Signaling Pathway
wikipathwaysWP2572Primary Focal Segmental Glomerulosclerosis FSGS
wikipathwaysWP2586Aryl Hydrocarbon Receptor
wikipathwaysWP2828Bladder Cancer
wikipathwaysWP2864Apoptosis-related network due to altered Notch3 in ovarian cancer
wikipathwaysWP2877Vitamin D Receptor Pathway
wikipathwaysWP3565DNA Damage-Telomere Stress Induced Senescence
wikipathwaysWP3596miR-517 relationship with ARCN1 and USP1
wikipathwaysWP3611Photodynamic therapy-induced AP-1 survival signaling.
wikipathwaysWP3646Hepatitis C and Hepatocellular Carcinoma
wikipathwaysWP366TGF-beta Signaling Pathway
wikipathwaysWP3672LncRNA-mediated mechanisms of therapeutic resistance
wikipathwaysWP3680Association Between Physico-Chemical Features and Toxicity Associated Pathways
wikipathwaysWP3804TP53 Regulates Transcription of Cell Cycle Genes
wikipathwaysWP3932Focal Adhesion-PI3K-Akt-mTOR-signaling pathway
wikipathwaysWP3941Oxidative Damage
wikipathwaysWP3981miRNA regulation of prostate cancer signaling pathways
wikipathwaysWP4010Liver steatosis AOP
wikipathwaysWP4066Interleukin-4 and 13 signaling
wikipathwaysWP4086Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
wikipathwaysWP4107Transcriptional regulation by RUNX3
wikipathwaysWP4155Endometrial cancer
wikipathwaysWP4172PI3K-Akt Signaling Pathway
wikipathwaysWP4216Chromosomal and microsatellite instability in colorectal cancer
wikipathwaysWP4241Type 2 papillary renal cell carcinoma
wikipathwaysWP45G1 to S cell cycle control
wikipathwaysWP61Notch Signaling Pathway
wikipathwaysWP615Senescence and Autophagy in Cancer
wikipathwaysWP673ErbB Signaling Pathway
wikipathwaysWP707DNA Damage Response
wikipathwaysWP710DNA Damage Response (only ATM dependent)
kegghsa04012ErbB signaling pathway - Homo sapiens (human)
kegghsa04066HIF-1 signaling pathway - Homo sapiens (human)
kegghsa04068FoxO signaling pathway - Homo sapiens (human)
kegghsa04110Cell cycle - Homo sapiens (human)
kegghsa04115p53 signaling pathway - Homo sapiens (human)
kegghsa04151PI3K-Akt signaling pathway - Homo sapiens (human)
kegghsa04218Cellular senescence - Homo sapiens (human)
kegghsa04630Jak-STAT signaling pathway - Homo sapiens (human)
kegghsa04921Oxytocin signaling pathway - Homo sapiens (human)
kegghsa04934Cushing,s syndrome - Homo sapiens (human)
kegghsa05160Hepatitis C - Homo sapiens (human)
kegghsa05161Hepatitis B - Homo sapiens (human)
kegghsa05165Human papillomavirus infection - Homo sapiens (human)
kegghsa05166HTLV-I infection - Homo sapiens (human)
kegghsa05167Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
kegghsa05169Epstein-Barr virus infection - Homo sapiens (human)
kegghsa05200Pathways in cancer - Homo sapiens (human)
kegghsa05202Transcriptional misregulation in cancer - Homo sapiens (human)
kegghsa05203Viral carcinogenesis - Homo sapiens (human)
kegghsa05205Proteoglycans in cancer - Homo sapiens (human)
kegghsa05206MicroRNAs in cancer - Homo sapiens (human)
kegghsa05210Colorectal cancer - Homo sapiens (human)
kegghsa05211Renal cell carcinoma - Homo sapiens (human)
kegghsa05212Pancreatic cancer - Homo sapiens (human)
kegghsa05213Endometrial cancer - Homo sapiens (human)
kegghsa05214Glioma - Homo sapiens (human)
kegghsa05215Prostate cancer - Homo sapiens (human)
kegghsa05216Thyroid cancer - Homo sapiens (human)
kegghsa05217Basal cell carcinoma - Homo sapiens (human)
kegghsa05218Melanoma - Homo sapiens (human)
kegghsa05219Bladder cancer - Homo sapiens (human)
kegghsa05220Chronic myeloid leukemia - Homo sapiens (human)
kegghsa05222Small cell lung cancer - Homo sapiens (human)
kegghsa05223Non-small cell lung cancer - Homo sapiens (human)
kegghsa05224Breast cancer - Homo sapiens (human)
kegghsa05225Hepatocellular carcinoma - Homo sapiens (human)
kegghsa05226Gastric cancer - Homo sapiens (human)
reactomeR-HSA-1257604PIP3 activates AKT signaling
reactomeR-HSA-1280215Cytokine Signaling in Immune system
reactomeR-HSA-162582Signal Transduction
reactomeR-HSA-1640170Cell Cycle
reactomeR-HSA-168256Immune System
reactomeR-HSA-187577SCF(Skp2)-mediated degradation of p27/p21
reactomeR-HSA-198323AKT phosphorylates targets in the cytosol
reactomeR-HSA-212436Generic Transcription Pathway
reactomeR-HSA-2219528PI3K/AKT Signaling in Cancer
reactomeR-HSA-2262752Cellular responses to stress
reactomeR-HSA-2559582Senescence-Associated Secretory Phenotype (SASP)
reactomeR-HSA-2559583Cellular Senescence
reactomeR-HSA-2559586DNA Damage/Telomere Stress Induced Senescence
reactomeR-HSA-3700989Transcriptional Regulation by TP53
reactomeR-HSA-449147Signaling by Interleukins
reactomeR-HSA-453274Mitotic G2-G2/M phases
reactomeR-HSA-453279Mitotic G1-G1/S phases
reactomeR-HSA-5663202Diseases of signal transduction
reactomeR-HSA-5674400Constitutive Signaling by AKT1 E17K in Cancer
reactomeR-HSA-6785807Interleukin-4 and Interleukin-13 signaling
reactomeR-HSA-6791312TP53 Regulates Transcription of Cell Cycle Genes
reactomeR-HSA-6804116TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
reactomeR-HSA-69202Cyclin E associated events during G1/S transition
reactomeR-HSA-69206G1/S Transition
reactomeR-HSA-69231Cyclin D associated events in G1
reactomeR-HSA-69236G1 Phase
reactomeR-HSA-69242S Phase
reactomeR-HSA-69275G2/M Transition
reactomeR-HSA-69278Cell Cycle, Mitotic
reactomeR-HSA-69560Transcriptional activation of p53 responsive genes
reactomeR-HSA-69563p53-Dependent G1 DNA Damage Response
reactomeR-HSA-69580p53-Dependent G1/S DNA damage checkpoint
reactomeR-HSA-69615G1/S DNA Damage Checkpoints
reactomeR-HSA-69620Cell Cycle Checkpoints
reactomeR-HSA-69656Cyclin A:Cdk2-associated events at S phase entry
reactomeR-HSA-69895Transcriptional activation of cell cycle inhibitor p21
reactomeR-HSA-73857RNA Polymerase II Transcription
reactomeR-HSA-74160Gene expression (Transcription)
reactomeR-HSA-8852276The role of GTSE1 in G2/M progression after G2 checkpoint
reactomeR-HSA-8864260Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
reactomeR-HSA-8866911TFAP2 (AP-2) family regulates transcription of cell cycle factors
reactomeR-HSA-8878159Transcriptional regulation by RUNX3
reactomeR-HSA-8878166Transcriptional regulation by RUNX2
reactomeR-HSA-8941855RUNX3 regulates CDKN1A transcription
reactomeR-HSA-8953897Cellular responses to external stimuli
reactomeR-HSA-9006925Intracellular signaling by second messengers
biocartacalcineurinpathwayeffects of calcineurin in keratinocyte differentiation
biocartacellcyclepathwaycyclins and cell cycle regulation
biocartaeponfkbpathwayerythropoietin mediated neuroprotection through nf-kb
biocartag1pathwaycell cycle: g1/s check point
biocartag2pathwaycell cycle: g2/m checkpoint
biocartap53hypoxiapathwayhypoxia and p53 in the cardiovascular system
biocartap53pathwayp53 signaling pathway
biocartaraccycdpathwayinfluence of ras and rho proteins on g1 to s transition
biocartarbpathwayrb tumor suppressor/checkpoint signaling in response to dna damage

Gene-Drug: Aster Plot

Drug IDDrug NameModel Num.
iGMDRD180CDK2/4 inhibitor6
iGMDRD886Compound 1541A3
iGMDRD286Nsc 6328397

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in CDKN1A