CDKN1A
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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| cyclin dependent kinase inhibitor 1A | MIM:116899 | Ensembl:ENSG00000124762 | HGNC:HGNC:1784 | PA104 | 6p21.2 |
GO terms in CDKN1A
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | EXP | GO:0004693 | cyclin-dependent protein serine/threonine kinase activity |
| MF | IMP | GO:0004860 | protein kinase inhibitor activity |
| MF | TAS | GO:0004861 | cyclin-dependent protein serine/threonine kinase inhibitor activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IPI | GO:0019901 | protein kinase binding |
| MF | IDA | GO:0019912 | cyclin-dependent protein kinase activating kinase activity |
| MF | IEA | GO:0030332 | cyclin binding |
| MF | IPI | GO:0031625 | ubiquitin protein ligase binding |
| MF | IPI | GO:0044877 | protein-containing complex binding |
| MF | IEA | GO:0046872 | metal ion binding |
| BP | TAS | GO:0000079 | regulation of cyclin-dependent protein serine/threonine kinase activity |
| BP | IDA | GO:0000082 | G1/S transition of mitotic cell cycle |
| BP | TAS | GO:0000082 | G1/S transition of mitotic cell cycle |
| BP | IMP | GO:0000086 | G2/M transition of mitotic cell cycle |
| BP | TAS | GO:0006357 | regulation of transcription by RNA polymerase II |
| BP | TAS | GO:0006367 | transcription initiation from RNA polymerase II promoter |
| BP | IMP | GO:0006974 | cellular response to DNA damage stimulus |
| BP | IDA | GO:0006977 | DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest |
| BP | TAS | GO:0006977 | DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest |
| BP | IEA | GO:0006978 | DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator |
| BP | IDA | GO:0007050 | cell cycle arrest |
| BP | IMP | GO:0007050 | cell cycle arrest |
| BP | IEP | GO:0007265 | Ras protein signal transduction |
| BP | IDA | GO:0008285 | negative regulation of cell proliferation |
| BP | IMP | GO:0008285 | negative regulation of cell proliferation |
| BP | IEA | GO:0009636 | response to toxic substance |
| BP | IEA | GO:0010165 | response to X-ray |
| BP | IEA | GO:0010243 | response to organonitrogen compound |
| BP | IEA | GO:0010629 | negative regulation of gene expression |
| BP | TAS | GO:0019221 | cytokine-mediated signaling pathway |
| BP | IDA | GO:0030308 | negative regulation of cell growth |
| BP | IEA | GO:0030890 | positive regulation of B cell proliferation |
| BP | IEA | GO:0031100 | animal organ regeneration |
| BP | IMP | GO:0031668 | cellular response to extracellular stimulus |
| BP | IEA | GO:0033158 | regulation of protein import into nucleus, translocation |
| BP | IMP | GO:0034198 | cellular response to amino acid starvation |
| BP | IEA | GO:0034605 | cellular response to heat |
| BP | IDA | GO:0042326 | negative regulation of phosphorylation |
| BP | IEA | GO:0042493 | response to drug |
| BP | IEA | GO:0042771 | intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator |
| BP | IEA | GO:0043066 | negative regulation of apoptotic process |
| BP | IEA | GO:0043068 | positive regulation of programmed cell death |
| BP | IEA | GO:0045736 | negative regulation of cyclin-dependent protein serine/threonine kinase activity |
| BP | IDA | GO:0045860 | positive regulation of protein kinase activity |
| BP | IEA | GO:0046685 | response to arsenic-containing substance |
| BP | IMP | GO:0048146 | positive regulation of fibroblast proliferation |
| BP | TAS | GO:0050821 | protein stabilization |
| BP | IEA | GO:0051412 | response to corticosterone |
| BP | IEA | GO:0055093 | response to hyperoxia |
| BP | IEA | GO:0060574 | intestinal epithelial cell maturation |
| BP | IMP | GO:0071479 | cellular response to ionizing radiation |
| BP | IEA | GO:0071480 | cellular response to gamma radiation |
| BP | ISS | GO:0071493 | cellular response to UV-B |
| BP | IEA | GO:0071850 | mitotic cell cycle arrest |
| BP | IMP | GO:0090398 | cellular senescence |
| BP | IEA | GO:0090399 | replicative senescence |
| BP | TAS | GO:0090400 | stress-induced premature senescence |
| BP | TAS | GO:0097193 | intrinsic apoptotic signaling pathway |
| BP | IMP | GO:1904030 | negative regulation of cyclin-dependent protein kinase activity |
| BP | IEA | GO:1904031 | positive regulation of cyclin-dependent protein kinase activity |
| BP | IMP | GO:1904706 | negative regulation of vascular smooth muscle cell proliferation |
| BP | IGI | GO:2000134 | negative regulation of G1/S transition of mitotic cell cycle |
| BP | IEA | GO:2000278 | regulation of DNA biosynthetic process |
| BP | IMP | GO:2000379 | positive regulation of reactive oxygen species metabolic process |
| CC | IDA | GO:0000307 | cyclin-dependent protein kinase holoenzyme complex |
| CC | IDA | GO:0005634 | nucleus |
| CC | IDA | GO:0005654 | nucleoplasm |
| CC | TAS | GO:0005654 | nucleoplasm |
| CC | IDA | GO:0005730 | nucleolus |
| CC | TAS | GO:0005829 | cytosol |
| CC | IDA | GO:0016604 | nuclear body |
| CC | IDA | GO:0032991 | protein-containing complex |
| CC | IEA | GO:0048471 | perinuclear region of cytoplasm |
| CC | IDA | GO:0070557 | PCNA-p21 complex |
Gene expression in normal tissue: CDKN1A
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in CDKN1A
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| pid | angiopoietinreceptor_pathway | Angiopoietin receptor Tie2-mediated signaling |
| pid | cmyb_pathway | C-MYB transcription factor network |
| pid | e2f_pathway | E2F transcription factor network |
| pid | hdac_classiii_pathway | Signaling events mediated by HDAC Class III |
| pid | myc_represspathway | Validated targets of C-MYC transcriptional repression |
| pid | notch_pathway | Notch signaling pathway |
| pid | p53downstreampathway | Direct p53 effectors |
| pid | p73pathway | p73 transcription factor network |
| pid | pi3kciaktpathway | Class I PI3K signaling events mediated by Akt |
| pid | prlsignalingeventspathway | Signaling events mediated by PRL |
| pid | rb_1pathway | Regulation of retinoblastoma protein |
| pid | reg_gr_pathway | Glucocorticoid receptor regulatory network |
| pid | smad2_3nuclearpathway | Regulation of nuclear SMAD2/3 signaling |
| pid | tap63pathway | Validated transcriptional targets of TAp63 isoforms |
| pharmgkb | PA152241951 | Celecoxib Pathway, Pharmacodynamics |
| smpdb | SMP00436 | Vinblastine Action Pathway |
| smpdb | SMP00437 | Vincristine Action Pathway |
| smpdb | SMP00438 | Vindesine Action Pathway |
| smpdb | SMP00439 | Vinorelbine Action Pathway |
| wikipathways | WP138 | Androgen receptor signaling pathway |
| wikipathways | WP1403 | AMP-activated Protein Kinase (AMPK) Signaling |
| wikipathways | WP1530 | miRNA Regulation of DNA Damage Response |
| wikipathways | WP1545 | miRNAs involved in DNA damage response |
| wikipathways | WP1742 | TP53 Network |
| wikipathways | WP1775 | Cell Cycle Checkpoints |
| wikipathways | WP179 | Cell Cycle |
| wikipathways | WP1971 | Integrated Cancer Pathway |
| wikipathways | WP2004 | miR-targeted genes in lymphocytes - TarBase |
| wikipathways | WP2005 | miR-targeted genes in muscle cell - TarBase |
| wikipathways | WP2261 | Signaling Pathways in Glioblastoma |
| wikipathways | WP236 | Adipogenesis |
| wikipathways | WP2446 | Retinoblastoma (RB) in Cancer |
| wikipathways | WP2516 | ATM Signaling Pathway |
| wikipathways | WP2572 | Primary Focal Segmental Glomerulosclerosis FSGS |
| wikipathways | WP2586 | Aryl Hydrocarbon Receptor |
| wikipathways | WP2828 | Bladder Cancer |
| wikipathways | WP2864 | Apoptosis-related network due to altered Notch3 in ovarian cancer |
| wikipathways | WP2877 | Vitamin D Receptor Pathway |
| wikipathways | WP3565 | DNA Damage-Telomere Stress Induced Senescence |
| wikipathways | WP3596 | miR-517 relationship with ARCN1 and USP1 |
| wikipathways | WP3611 | Photodynamic therapy-induced AP-1 survival signaling. |
| wikipathways | WP3646 | Hepatitis C and Hepatocellular Carcinoma |
| wikipathways | WP366 | TGF-beta Signaling Pathway |
| wikipathways | WP3672 | LncRNA-mediated mechanisms of therapeutic resistance |
| wikipathways | WP3680 | Association Between Physico-Chemical Features and Toxicity Associated Pathways |
| wikipathways | WP3804 | TP53 Regulates Transcription of Cell Cycle Genes |
| wikipathways | WP3932 | Focal Adhesion-PI3K-Akt-mTOR-signaling pathway |
| wikipathways | WP3941 | Oxidative Damage |
| wikipathways | WP3981 | miRNA regulation of prostate cancer signaling pathways |
| wikipathways | WP4010 | Liver steatosis AOP |
| wikipathways | WP4066 | Interleukin-4 and 13 signaling |
| wikipathways | WP4086 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors |
| wikipathways | WP4107 | Transcriptional regulation by RUNX3 |
| wikipathways | WP4155 | Endometrial cancer |
| wikipathways | WP4172 | PI3K-Akt Signaling Pathway |
| wikipathways | WP4216 | Chromosomal and microsatellite instability in colorectal cancer |
| wikipathways | WP4241 | Type 2 papillary renal cell carcinoma |
| wikipathways | WP45 | G1 to S cell cycle control |
| wikipathways | WP61 | Notch Signaling Pathway |
| wikipathways | WP615 | Senescence and Autophagy in Cancer |
| wikipathways | WP673 | ErbB Signaling Pathway |
| wikipathways | WP707 | DNA Damage Response |
| wikipathways | WP710 | DNA Damage Response (only ATM dependent) |
| netpath | Pathway_TGF_beta_Receptor | TGF_beta_Receptor |
| kegg | hsa04012 | ErbB signaling pathway - Homo sapiens (human) |
| kegg | hsa04066 | HIF-1 signaling pathway - Homo sapiens (human) |
| kegg | hsa04068 | FoxO signaling pathway - Homo sapiens (human) |
| kegg | hsa04110 | Cell cycle - Homo sapiens (human) |
| kegg | hsa04115 | p53 signaling pathway - Homo sapiens (human) |
| kegg | hsa04151 | PI3K-Akt signaling pathway - Homo sapiens (human) |
| kegg | hsa04218 | Cellular senescence - Homo sapiens (human) |
| kegg | hsa04630 | Jak-STAT signaling pathway - Homo sapiens (human) |
| kegg | hsa04921 | Oxytocin signaling pathway - Homo sapiens (human) |
| kegg | hsa04934 | Cushing,s syndrome - Homo sapiens (human) |
| kegg | hsa05160 | Hepatitis C - Homo sapiens (human) |
| kegg | hsa05161 | Hepatitis B - Homo sapiens (human) |
| kegg | hsa05165 | Human papillomavirus infection - Homo sapiens (human) |
| kegg | hsa05166 | HTLV-I infection - Homo sapiens (human) |
| kegg | hsa05167 | Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human) |
| kegg | hsa05169 | Epstein-Barr virus infection - Homo sapiens (human) |
| kegg | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05202 | Transcriptional misregulation in cancer - Homo sapiens (human) |
| kegg | hsa05203 | Viral carcinogenesis - Homo sapiens (human) |
| kegg | hsa05205 | Proteoglycans in cancer - Homo sapiens (human) |
| kegg | hsa05206 | MicroRNAs in cancer - Homo sapiens (human) |
| kegg | hsa05210 | Colorectal cancer - Homo sapiens (human) |
| kegg | hsa05211 | Renal cell carcinoma - Homo sapiens (human) |
| kegg | hsa05212 | Pancreatic cancer - Homo sapiens (human) |
| kegg | hsa05213 | Endometrial cancer - Homo sapiens (human) |
| kegg | hsa05214 | Glioma - Homo sapiens (human) |
| kegg | hsa05215 | Prostate cancer - Homo sapiens (human) |
| kegg | hsa05216 | Thyroid cancer - Homo sapiens (human) |
| kegg | hsa05217 | Basal cell carcinoma - Homo sapiens (human) |
| kegg | hsa05218 | Melanoma - Homo sapiens (human) |
| kegg | hsa05219 | Bladder cancer - Homo sapiens (human) |
| kegg | hsa05220 | Chronic myeloid leukemia - Homo sapiens (human) |
| kegg | hsa05222 | Small cell lung cancer - Homo sapiens (human) |
| kegg | hsa05223 | Non-small cell lung cancer - Homo sapiens (human) |
| kegg | hsa05224 | Breast cancer - Homo sapiens (human) |
| kegg | hsa05225 | Hepatocellular carcinoma - Homo sapiens (human) |
| kegg | hsa05226 | Gastric cancer - Homo sapiens (human) |
| reactome | R-HSA-1257604 | PIP3 activates AKT signaling |
| reactome | R-HSA-1280215 | Cytokine Signaling in Immune system |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-1640170 | Cell Cycle |
| reactome | R-HSA-1643685 | Disease |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 |
| reactome | R-HSA-198323 | AKT phosphorylates targets in the cytosol |
| reactome | R-HSA-212436 | Generic Transcription Pathway |
| reactome | R-HSA-2219528 | PI3K/AKT Signaling in Cancer |
| reactome | R-HSA-2262752 | Cellular responses to stress |
| reactome | R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) |
| reactome | R-HSA-2559583 | Cellular Senescence |
| reactome | R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence |
| reactome | R-HSA-3700989 | Transcriptional Regulation by TP53 |
| reactome | R-HSA-449147 | Signaling by Interleukins |
| reactome | R-HSA-453274 | Mitotic G2-G2/M phases |
| reactome | R-HSA-453279 | Mitotic G1-G1/S phases |
| reactome | R-HSA-5663202 | Diseases of signal transduction |
| reactome | R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer |
| reactome | R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling |
| reactome | R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes |
| reactome | R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest |
| reactome | R-HSA-69202 | Cyclin E associated events during G1/S transition |
| reactome | R-HSA-69206 | G1/S Transition |
| reactome | R-HSA-69231 | Cyclin D associated events in G1 |
| reactome | R-HSA-69236 | G1 Phase |
| reactome | R-HSA-69242 | S Phase |
| reactome | R-HSA-69275 | G2/M Transition |
| reactome | R-HSA-69278 | Cell Cycle, Mitotic |
| reactome | R-HSA-69560 | Transcriptional activation of p53 responsive genes |
| reactome | R-HSA-69563 | p53-Dependent G1 DNA Damage Response |
| reactome | R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint |
| reactome | R-HSA-69615 | G1/S DNA Damage Checkpoints |
| reactome | R-HSA-69620 | Cell Cycle Checkpoints |
| reactome | R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry |
| reactome | R-HSA-69895 | Transcriptional activation of cell cycle inhibitor p21 |
| reactome | R-HSA-73857 | RNA Polymerase II Transcription |
| reactome | R-HSA-74160 | Gene expression (Transcription) |
| reactome | R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint |
| reactome | R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors |
| reactome | R-HSA-8866911 | TFAP2 (AP-2) family regulates transcription of cell cycle factors |
| reactome | R-HSA-8878159 | Transcriptional regulation by RUNX3 |
| reactome | R-HSA-8878166 | Transcriptional regulation by RUNX2 |
| reactome | R-HSA-8941855 | RUNX3 regulates CDKN1A transcription |
| reactome | R-HSA-8953897 | Cellular responses to external stimuli |
| reactome | R-HSA-9006925 | Intracellular signaling by second messengers |
| biocarta | calcineurinpathway | effects of calcineurin in keratinocyte differentiation |
| biocarta | cellcyclepathway | cyclins and cell cycle regulation |
| biocarta | eponfkbpathway | erythropoietin mediated neuroprotection through nf-kb |
| biocarta | g1pathway | cell cycle: g1/s check point |
| biocarta | g2pathway | cell cycle: g2/m checkpoint |
| biocarta | p53hypoxiapathway | hypoxia and p53 in the cardiovascular system |
| biocarta | p53pathway | p53 signaling pathway |
| biocarta | raccycdpathway | influence of ras and rho proteins on g1 to s transition |
| biocarta | rbpathway | rb tumor suppressor/checkpoint signaling in response to dna damage |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD180 | CDK2/4 inhibitor | 6 |
| iGMDRD494 | Neopeltolide | 3 |
| iGMDRD330 | BRD4132 | 3 |
| iGMDRD1002 | rTRAIL | 1 |
| iGMDRD132 | (-)-gallocatechin-3-O-gallate | 4 |
| iGMDRD154 | NSC23766 | 3 |
| iGMDRD21 | Fluorouracil | 1 |
| iGMDRD782 | DC-45-A2 | 2 |
| iGMDRD434 | BMS-536924 | 6 |
| iGMDRD255 | SB225002 | 3 |
| iGMDRD268 | Cerulenin | 3 |
| iGMDRD886 | Compound 1541A | 3 |
| iGMDRD60 | Quinoclamine | 3 |
| iGMDRD506 | Fedratinib | 8 |
| iGMDRD366 | PI-103 | 7 |
| iGMDRD562 | Navitoclax | 2 |
| iGMDRD286 | Nsc 632839 | 7 |
| iGMDRD188 | Piperlongumine | 2 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in CDKN1A
CLASSFICATION
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