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FLASH GENE
Symbol CDK4 contributors: mct/ - updated : 12-02-2014
HGNC name cyclin-dependent kinase 4
HGNC id 1773
Corresponding disease
CMM3 hereditary malignant melanoma
Location 12q14.1      Physical location : 58.142.004 - 58.146.164
Synonym name cell division kinase 4
Synonym symbol(s) MGC14458, PSK-J3, CMM3
EC.number 2.7.11.22
DNA
TYPE functioning gene
STRUCTURE 4.72 kb     8 Exon(s)
10 Kb 5' upstream gene genomic sequence study
text structure Exons coding : 7
MAPPING cloned Y linked N status confirmed
Map cen - D12S1707 - D12S1410 - RPS26 - D12S1177E - D12S1644 - D12S1268 - DDIT3 DDIT3 , GLI - B4GALNT1 - KIF5A - TSPAN31 - CDK4 - D12S1197E - D12S90 - D12S1529 - D12S1438 - (D12S305 ,D12S104 ) - D12S72 - D12S1446 - D12S1829 - D12S355 - D12S1298 - D12S1277 - D12S1989 - D12S1700 - D12S1169E - D12S1072 - D12S1662 - D12S83 - qter
Physical map
INHBC 12q13.1 inhibin, beta C INHBE 12q13.2 inhibin, beta E GLI 12q13.3-q14.1 glioma-associated oncogene homolog (zinc finger protein) ARHGAP9 12q14 Rho GTPase activating protein 9 MARS 12q13.11-q14.3 methionine-tRNA synthetase DDIT3 12q13.1-q13.2 DNA-damage-inducible transcript 3 MBD6 12q13.2 methyl-CpG binding domain protein 6 DCTN2 12q13.2-q13.3 dynactin 2 (p50) KIF5A 12q13 kinesin family member 5A PIP5K2C 12q13.2 phosphatidylinositol-4-phosphate 5-kinase, type II, gamma FLJ34766 GEFT 12q13.2 RAC/CDC42 exchange factor SLC26A10 12q13 solute carrier family 26, member 10 GALGT 12q13.3 UDP-N-acetyl-alpha-D-galactosamine:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase (GalNAc-T) LOC390333 12 similar to ribosomal protein L13a; 60S ribosomal protein L13a; 23 kD highly basic protein OS-9 12q13 amplified in osteosarcoma CENTG1 12q13.3 centaurin, gamma 1 SAS 12q13-q14 sarcoma amplified sequence CDK4 12q14 cyclin-dependent kinase 4 LOC92979 12q13.2 hypothetical protein BC009489 CYP27B1 12q13-q14 cytochrome P450, family 27, subfamily B, polypeptide 1 METTL1 12q13 methyltransferase-like 1 DKFZP586D0919 12q13.2 hepatocellularcarcinoma-associated antigen HCA557a TSFM 12q13-q14 Ts translation elongation factor, mitochondrial AVIL 12q13.13 advillin CTDSP2 12q13-q15 . CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase 2 KUB3 12q13.2 Ku70-binding protein 3 LOC338805 12q13.2 similar to heat shock 70kD protein binding protein; progesterone receptor-associated p48 protein; putative tumor suppressor ST13; Hsp70-interacting protein
RNA
TRANSCRIPTS type messenger
text two alternatively spliced variants and multiple polyadenylation sites
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 1474 33.6 303 - 2009 19237565
- - 1122 - 111 - -
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestiveliver   highly
Nervousbrain   highly
Respiratorylung   highly
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connective    
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
cell cycle     cell cycle, checkpoint, G1S
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a PV/ISTVRE motif
  • HOMOLOGY
    interspecies ortholog to yeast S.cerevisiae cdc28
    Homologene
    FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • CDC2/CDKX subfamily
  • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • serine/threonine kinase, involved in cell cycle regulation (G1 to S transition)
  • essential for the G1- to S-phase transition during the cell cycle and its expression is primarily controlled at the transcriptional level
  • key regulator of the transition through the G(1) phase of the cell cycle
  • controls beta-cell mass by recruiting quiescent cells to enter the cell cycle
  • plays a previously unrecognized role in thymocyte maturation and adhesion, but is not required for thymocyte proliferation and is not required for lymphocyte trafficking to the lung following allergen sensitization and challenge ((
  • CCND1-CDK4 axis is not only critical in glial tumor cells but also in stromal-derived cells in the surrounding tumor microenvironment that are vital to sustain tumor outgrowth
  • CELLULAR PROCESS cell cycle, progression
    nucleotide, repair
    PHYSIOLOGICAL PROCESS
    text negative control
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with cyclins D (D1, D2, D3)
  • cyclin D2 and CDK4 formed a complex in the cytoplasm and approached the nucleus
  • CDK2/CDK4/NPM pathway is a major guardian of centrosome dysfunction and genomic integrity
  • CCND1-CDK4 axis is not only critical in glial tumor cells but also in stromal-derived cells in the surrounding tumor microenvironment that are vital to sustain tumor outgrowth
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • target by MYC phosphorylating and blocking active repression by RB1
  • ZNF655
  • bound to cyclin D1 and has a phosphorylated T-loop, but is in an inactive conformation
  • YY1 inhibited CDKN1A complex formation with CDK4 and CCND1
  • UCHL1 physically interacts with CDK1, CDK4, and CDK5, enhancing their kinase activity
  • novel function of CCND1 in promoting cell cycle progression by enhancing STK38/STK38L kinase activity independent of CDK4
  • RUNX1T1 controls proliferation and the neurotoxic effect of microglia by epigenetically regulating CDK4 and LAT2 via its interaction with HDACs
  • cell & other
    REGULATION
    inhibited by PPP3CA (inhibits the kinase activity of CDK4 by preventing its reassociation into an active kinase complex by utilizing common association domains used by cyclin D and CDKN2A)
    repressed by JUND (increased JunD in polyamine-deficient cells was associated with a significant inhibition of CDK4 transcription, as indicated by repression of CDK4-promoter activity and decreased levels of CDK4 mRNA and protein)
    ASSOCIATED DISORDERS
    corresponding disease(s) CMM3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in malignant glioblastoma, anaplastic astrocytoma, in diffuse large B cell lymphoma, osteosarcoma with OS9, SAS and PRIM1 and in sporadic breast carcinoma
    constitutional     --low  
    in insulin deficient diabete
    Susceptibility predisposing to familial melanoma by inducing abnormal repair of ultraviolet
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Cdk4-deficient mice display beta-cell hypoplasia and develop diabetes, whereas beta-cell hyperplasia is observed in mice expressing an active Cdk4R24C kinase