CDK4
Summary: The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. [provided by RefSeq, Jul 2008].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| cyclin dependent kinase 4 | MIM:123829 | Ensembl:ENSG00000135446 | HGNC:HGNC:1773 | PA102 | 12q14.1 |
GO terms in CDK4
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| CC | IDA | GO:0000307 | cyclin-dependent protein kinase holoenzyme complex |
| CC | IDA | GO:0000785 | chromatin |
| CC | IBA | GO:0005634 | nucleus |
| CC | IDA | GO:0005634 | nucleus |
| CC | TAS | GO:0005654 | nucleoplasm |
| CC | IEA | GO:0005667 | transcription factor complex |
| CC | IDA | GO:0005730 | nucleolus |
| CC | IDA | GO:0005829 | cytosol |
| CC | TAS | GO:0005829 | cytosol |
| CC | IEA | GO:0005923 | bicellular tight junction |
| CC | IDA | GO:0031965 | nuclear membrane |
| CC | IEA | GO:0048471 | perinuclear region of cytoplasm |
| CC | IEA | GO:0097129 | cyclin D2-CDK4 complex |
| BP | IMP | GO:0000082 | G1/S transition of mitotic cell cycle |
| BP | IEA | GO:0002088 | lens development in camera-type eye |
| BP | TAS | GO:0006367 | transcription initiation from RNA polymerase II promoter |
| BP | IBA | GO:0006468 | protein phosphorylation |
| BP | IDA | GO:0006468 | protein phosphorylation |
| BP | IEA | GO:0007623 | circadian rhythm |
| BP | IMP | GO:0008284 | positive regulation of cell proliferation |
| BP | IEA | GO:0009636 | response to toxic substance |
| BP | IEA | GO:0010288 | response to lead ion |
| BP | IMP | GO:0010468 | regulation of gene expression |
| BP | IDA | GO:0010971 | positive regulation of G2/M transition of mitotic cell cycle |
| BP | IEA | GO:0031100 | animal organ regeneration |
| BP | TAS | GO:0031658 | negative regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle |
| BP | IEA | GO:0032869 | cellular response to insulin stimulus |
| BP | IEA | GO:0033574 | response to testosterone |
| BP | IEA | GO:0040014 | regulation of multicellular organism growth |
| BP | IEP | GO:0042493 | response to drug |
| BP | IEA | GO:0043065 | positive regulation of apoptotic process |
| BP | IEA | GO:0045727 | positive regulation of translation |
| BP | TAS | GO:0045787 | positive regulation of cell cycle |
| BP | IEA | GO:0045793 | positive regulation of cell size |
| BP | IEA | GO:0046626 | regulation of insulin receptor signaling pathway |
| BP | IEA | GO:0046890 | regulation of lipid biosynthetic process |
| BP | IMP | GO:0048146 | positive regulation of fibroblast proliferation |
| BP | IEA | GO:0050994 | regulation of lipid catabolic process |
| BP | IEA | GO:0051301 | cell division |
| BP | IEA | GO:0055093 | response to hyperoxia |
| BP | IEA | GO:0060612 | adipose tissue development |
| BP | IDA | GO:0071157 | negative regulation of cell cycle arrest |
| BP | IEA | GO:0071222 | cellular response to lipopolysaccharide |
| BP | IEA | GO:0071353 | cellular response to interleukin-4 |
| BP | IEA | GO:1904628 | cellular response to phorbol 13-acetate 12-myristate |
| BP | IEA | GO:1904637 | cellular response to ionomycin |
| MF | EXP | GO:0004693 | cyclin-dependent protein serine/threonine kinase activity |
| MF | IBA | GO:0004693 | cyclin-dependent protein serine/threonine kinase activity |
| MF | IDA | GO:0004693 | cyclin-dependent protein serine/threonine kinase activity |
| MF | TAS | GO:0004693 | cyclin-dependent protein serine/threonine kinase activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IEA | GO:0005524 | ATP binding |
| MF | TAS | GO:0016538 | cyclin-dependent protein serine/threonine kinase regulator activity |
| MF | IPI | GO:0030332 | cyclin binding |
| MF | IEA | GO:0044877 | protein-containing complex binding |
Gene expression in normal tissue: CDK4
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in CDK4
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| reactome | R-HSA-1266738 | Developmental Biology |
| reactome | R-HSA-1474165 | Reproduction |
| reactome | R-HSA-1500620 | Meiosis |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-1640170 | Cell Cycle |
| reactome | R-HSA-1640170 | Cell Cycle |
| reactome | R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 |
| reactome | R-HSA-212436 | Generic Transcription Pathway |
| reactome | R-HSA-2262752 | Cellular responses to stress |
| reactome | R-HSA-2559580 | Oxidative Stress Induced Senescence |
| reactome | R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) |
| reactome | R-HSA-2559583 | Cellular Senescence |
| reactome | R-HSA-2559585 | Oncogene Induced Senescence |
| reactome | R-HSA-3214858 | RMTs methylate histone arginines |
| reactome | R-HSA-3247509 | Chromatin modifying enzymes |
| reactome | R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation |
| reactome | R-HSA-453279 | Mitotic G1-G1/S phases |
| reactome | R-HSA-4839726 | Chromatin organization |
| reactome | R-HSA-69202 | Cyclin E associated events during G1/S transition |
| reactome | R-HSA-69206 | G1/S Transition |
| reactome | R-HSA-69229 | Ubiquitin-dependent degradation of Cyclin D1 |
| reactome | R-HSA-69229 | Ubiquitin-dependent degradation of Cyclin D1 |
| 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-69242 | S Phase |
| reactome | R-HSA-69278 | Cell Cycle, Mitotic |
| reactome | R-HSA-69278 | Cell Cycle, Mitotic |
| reactome | R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry |
| reactome | R-HSA-73857 | RNA Polymerase II Transcription |
| reactome | R-HSA-74160 | Gene expression (Transcription) |
| reactome | R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D |
| reactome | R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D |
| reactome | R-HSA-8848021 | Signaling by PTK6 |
| reactome | R-HSA-8849470 | PTK6 Regulates Cell Cycle |
| reactome | R-HSA-8878166 | Transcriptional regulation by RUNX2 |
| reactome | R-HSA-8953897 | Cellular responses to external stimuli |
| reactome | R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases |
| reactome | R-HSA-912446 | Meiotic recombination |
| biocarta | cellcyclepathway | cyclins and cell cycle regulation |
| biocarta | efppathway | estrogen responsive protein efp controls cell cycle and breast tumors growth |
| biocarta | g1pathway | cell cycle: g1/s check point |
| 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 |
| 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 | hsa04530 | Tight junction - Homo sapiens (human) |
| kegg | hsa04660 | T cell receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04933 | AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human) |
| kegg | hsa04934 | Cushing,s syndrome - Homo sapiens (human) |
| kegg | hsa05161 | Hepatitis B - Homo sapiens (human) |
| kegg | hsa05162 | Measles - 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 | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05203 | Viral carcinogenesis - Homo sapiens (human) |
| kegg | hsa05212 | Pancreatic cancer - Homo sapiens (human) |
| kegg | hsa05214 | Glioma - 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) |
| pid | atf2_pathway | ATF-2 transcription factor network |
| pid | foxm1pathway | FOXM1 transcription factor network |
| pid | myc_activpathway | Validated targets of C-MYC transcriptional activation |
| pid | nfat_tfpathway | Calcineurin-regulated NFAT-dependent transcription in lymphocytes |
| pid | rb_1pathway | Regulation of retinoblastoma protein |
| pid | smad2_3nuclearpathway | Regulation of nuclear SMAD2/3 signaling |
| netpath | Pathway_BCR | BCR |
| netpath | Pathway_TGF_beta_Receptor | TGF_beta_Receptor |
| wikipathways | WP1530 | miRNA Regulation of DNA Damage Response |
| wikipathways | WP179 | Cell Cycle |
| wikipathways | WP2032 | Human Thyroid Stimulating Hormone (TSH) signaling pathway |
| wikipathways | WP2261 | Signaling Pathways in Glioblastoma |
| wikipathways | WP2431 | Spinal Cord Injury |
| wikipathways | WP2446 | Retinoblastoma (RB) in Cancer |
| wikipathways | WP2828 | Bladder Cancer |
| wikipathways | WP2878 | PPAR Alpha Pathway |
| wikipathways | WP2882 | Nuclear Receptors Meta-Pathway |
| wikipathways | WP34 | Ovarian Infertility Genes |
| wikipathways | WP3863 | T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection |
| wikipathways | WP3969 | H19 action Rb-E2F1 signaling and CDK-?-catenin activity |
| wikipathways | WP4172 | PI3K-Akt Signaling Pathway |
| wikipathways | WP4204 | Tumor suppressor activity of SMARCB1 |
| wikipathways | WP45 | G1 to S cell cycle control |
| wikipathways | WP707 | DNA Damage Response |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD42 | Vorinostat | 2 |
| iGMDRD300 | Tozasertib | 3 |
| iGMDRD935 | JQ12 | 1 |
| iGMDRD271 | Brefeldin A | 3 |
| iGMDRD481 | Dactolisib | 1 |
| iGMDRD551 | Ponatinib | 1 |
| iGMDRD267 | Oligomycin A | 8 |
| iGMDRD231 | Importazole | 3 |
| iGMDRD6 | AM-580 | 1 |
| iGMDRD536 | PLX-4720 | 2 |
| iGMDRD351 | GW843682X | 1 |
| iGMDRD499 | PDMP | 1 |
| iGMDRD435 | BI-2536 | 1 |
| iGMDRD512 | nutlin 3 | 3 |
| iGMDRD701 | NVP-AUY922 | 1 |
| iGMDRD116 | CD437 | 1 |
| iGMDRD577 | BIX01294 | 3 |
| iGMDRD562 | Navitoclax | 8 |
| iGMDRD887 | Compound 23 citrate | 3 |
| iGMDRD60 | Quinoclamine | 5 |
| iGMDRD255 | SB225002 | 1 |
| iGMDRD138 | PX 12 | 1 |
| iGMDRD318 | PAC-1 | 3 |
| iGMDRD727 | Alpelisib | 1 |
| iGMDRD309 | 17AAG | 1 |
| iGMDRD782 | DC-45-A2 | 3 |
| iGMDRD193 | Fqi1 | 1 |
| iGMDRD446 | LY 2183240 | 3 |
| iGMDRD797 | ISOX DUAL | 2 |
| iGMDRD375 | GW-405833 | 3 |
| iGMDRD181 | CDK4 inhibitor | 1 |
| iGMDRD229 | B02 | 1 |
| iGMDRD599 | Salermide | 1 |
| iGMDRD1008 | SR-II-138A | 1 |
| iGMDRD136 | Nutlin-3 | 1 |
| iGMDRD129 | SB-216763 | 1 |
| iGMDRD144 | NSC95397 | 3 |
| iGMDRD638 | Ribociclib | 18 |
| iGMDRD662 | JQ-1 | 3 |
| iGMDRD367 | Ro 28-1675 | 1 |
| iGMDRD552 | AZD-1775 | 1 |
| iGMDRD5 | Tyrphostin AG 1478 | 1 |
| iGMDRD103 | SN-38 | 3 |
| iGMDRD121 | GMX1778 | 3 |
| iGMDRD202 | Curcumin | 1 |
| iGMDRD251 | ML162 | 1 |
| iGMDRD311 | Dacinostat | 1 |
| iGMDRD705 | Nakiterpiosin | 3 |
| iGMDRD352 | PD-0325901 | 1 |
| iGMDRD698 | Neratinib | 1 |
| iGMDRD237 | ABT-751 | 1 |
| iGMDRD219 | Bax channel blocker | 3 |
| iGMDRD883 | CIL55A | 3 |
| iGMDRD123 | Isoevodiamine | 1 |
| iGMDRD523 | Cyanoquinoline, 11 | 1 |
| iGMDRD506 | Fedratinib | 1 |
| iGMDRD399 | Selumetinib | 1 |
| iGMDRD182 | CDK4 inhibitor (tumors with RB expression) | 1 |
| iGMDRD356 | PNU-74654 | 3 |
| iGMDRD524 | ISX-9 | 1 |
| iGMDRD190 | Nilotinib | 1 |
| iGMDRD64 | Parbendazole | 1 |
| iGMDRD260 | FQI-2 | 3 |
| iGMDRD52 | Rotenone | 1 |
| iGMDRD284 | Palbociclib | 7 |
| iGMDRD639 | YK 4-279 | 3 |
| iGMDRD152 | 179324-69-7 | 1 |
| iGMDRD61 | Kinetin riboside | 3 |
| iGMDRD2 | PK-11195 | 3 |
| iGMDRD466 | Chaetocin | 3 |
| iGMDRD394 | BX-795 | 3 |
| iGMDRD126 | Tipifarnib | 3 |
| iGMDRD433 | Lexibulin | 3 |
| iGMDRD151 | CHM-1 | 3 |
| iGMDRD781 | Sirolimus | 5 |
| iGMDRD546 | BMS-754807 | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in CDK4
CLASSFICATION
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