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Browse CDK6

Summary
SymbolCDK6
Namecyclin-dependent kinase 6
Aliases PLSTIRE; MCPH12; cell division protein kinase 6; serine/threonine-protein kinase PLSTIRE
Chromosomal Location7q21-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Nucleus. Cell projection, ruffle. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome Note=Localized to the ruffling edge of spreading fibroblasts. Kinase activity only in nucleus. Localized to the cytosol of neurons and showed prominent staining around either side of the nucleus (By similarity). Present in the cytosol and in the nucleus in interphase cells and at the centrosome during mitosis from prophase to telophase (PubMed:23918663).
Domain PF00069 Protein kinase domain
Function

Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663).

> Gene Ontology
 
Biological Process GO:0000082 G1/S transition of mitotic cell cycle
GO:0001503 ossification
GO:0001649 osteoblast differentiation
GO:0001952 regulation of cell-matrix adhesion
GO:0001954 positive regulation of cell-matrix adhesion
GO:0002064 epithelial cell development
GO:0002065 columnar/cuboidal epithelial cell differentiation
GO:0002066 columnar/cuboidal epithelial cell development
GO:0002067 glandular epithelial cell differentiation
GO:0002068 glandular epithelial cell development
GO:0002244 hematopoietic progenitor cell differentiation
GO:0002262 myeloid cell homeostasis
GO:0002521 leukocyte differentiation
GO:0002573 myeloid leukocyte differentiation
GO:0002683 negative regulation of immune system process
GO:0002761 regulation of myeloid leukocyte differentiation
GO:0002762 negative regulation of myeloid leukocyte differentiation
GO:0003309 type B pancreatic cell differentiation
GO:0003323 type B pancreatic cell development
GO:0007050 cell cycle arrest
GO:0007159 leukocyte cell-cell adhesion
GO:0007160 cell-matrix adhesion
GO:0007219 Notch signaling pathway
GO:0007568 aging
GO:0007569 cell aging
GO:0009615 response to virus
GO:0010001 glial cell differentiation
GO:0010810 regulation of cell-substrate adhesion
GO:0010811 positive regulation of cell-substrate adhesion
GO:0014002 astrocyte development
GO:0021537 telencephalon development
GO:0021542 dentate gyrus development
GO:0021543 pallium development
GO:0021591 ventricular system development
GO:0021670 lateral ventricle development
GO:0021761 limbic system development
GO:0021766 hippocampus development
GO:0021782 glial cell development
GO:0030098 lymphocyte differentiation
GO:0030099 myeloid cell differentiation
GO:0030217 T cell differentiation
GO:0030218 erythrocyte differentiation
GO:0030224 monocyte differentiation
GO:0030278 regulation of ossification
GO:0030279 negative regulation of ossification
GO:0030900 forebrain development
GO:0031016 pancreas development
GO:0031018 endocrine pancreas development
GO:0031589 cell-substrate adhesion
GO:0032844 regulation of homeostatic process
GO:0033077 T cell differentiation in thymus
GO:0034101 erythrocyte homeostasis
GO:0035270 endocrine system development
GO:0035883 enteroendocrine cell differentiation
GO:0042063 gliogenesis
GO:0042110 T cell activation
GO:0043696 dedifferentiation
GO:0043697 cell dedifferentiation
GO:0044770 cell cycle phase transition
GO:0044772 mitotic cell cycle phase transition
GO:0044843 cell cycle G1/S phase transition
GO:0045637 regulation of myeloid cell differentiation
GO:0045638 negative regulation of myeloid cell differentiation
GO:0045646 regulation of erythrocyte differentiation
GO:0045655 regulation of monocyte differentiation
GO:0045656 negative regulation of monocyte differentiation
GO:0045667 regulation of osteoblast differentiation
GO:0045668 negative regulation of osteoblast differentiation
GO:0045785 positive regulation of cell adhesion
GO:0045786 negative regulation of cell cycle
GO:0048144 fibroblast proliferation
GO:0048145 regulation of fibroblast proliferation
GO:0048146 positive regulation of fibroblast proliferation
GO:0048708 astrocyte differentiation
GO:0048863 stem cell differentiation
GO:0048872 homeostasis of number of cells
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050680 negative regulation of epithelial cell proliferation
GO:0060218 hematopoietic stem cell differentiation
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0071396 cellular response to lipid
GO:0071593 lymphocyte aggregation
GO:0071594 thymocyte aggregation
GO:0090342 regulation of cell aging
GO:0090344 negative regulation of cell aging
GO:0090398 cellular senescence
GO:1902105 regulation of leukocyte differentiation
GO:1902106 negative regulation of leukocyte differentiation
GO:1903131 mononuclear cell differentiation
GO:1903706 regulation of hemopoiesis
GO:1903707 negative regulation of hemopoiesis
GO:1904627 response to phorbol 13-acetate 12-myristate
GO:1904628 cellular response to phorbol 13-acetate 12-myristate
GO:2000772 regulation of cellular senescence
GO:2000773 negative regulation of cellular senescence
Molecular Function GO:0004674 protein serine/threonine kinase activity
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
GO:0030332 cyclin binding
GO:0097472 cyclin-dependent protein kinase activity
GO:0098770 FBXO family protein binding
Cellular Component GO:0000307 cyclin-dependent protein kinase holoenzyme complex
GO:0001726 ruffle
GO:0005813 centrosome
GO:0031252 cell leading edge
GO:0061695 transferase complex, transferring phosphorus-containing groups
GO:1902554 serine/threonine protein kinase complex
GO:1902911 protein kinase complex
> KEGG and Reactome Pathway
 
KEGG hsa04110 Cell cycle
hsa04115 p53 signaling pathway
hsa04151 PI3K-Akt signaling pathway
Reactome R-HSA-1640170: Cell Cycle
R-HSA-69278: Cell Cycle, Mitotic
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-69231: Cyclin D associated events in G1
R-HSA-69236: G1 Phase
R-HSA-453279: Mitotic G1-G1/S phases
R-HSA-2559585: Oncogene Induced Senescence
R-HSA-2559580: Oxidative Stress Induced Senescence
R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP)
Summary
SymbolCDK6
Namecyclin-dependent kinase 6
Aliases PLSTIRE; MCPH12; cell division protein kinase 6; serine/threonine-protein kinase PLSTIRE
Chromosomal Location7q21-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CDK6 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between CDK6 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26719346MelanomaInhibit immunity (infiltration)AURKAi and CDK4/6i promoted the recruitment of TILs by inducing CCL5 secretion in melanoma cells (P ≤ .005) in an NF-κB-dependent manner.
Summary
SymbolCDK6
Namecyclin-dependent kinase 6
Aliases PLSTIRE; MCPH12; cell division protein kinase 6; serine/threonine-protein kinase PLSTIRE
Chromosomal Location7q21-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of CDK6 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCDK6
Namecyclin-dependent kinase 6
Aliases PLSTIRE; MCPH12; cell division protein kinase 6; serine/threonine-protein kinase PLSTIRE
Chromosomal Location7q21-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CDK6 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0580.899
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.4180.78
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.4080.711
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.4030.187
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.7330.655
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.010.996
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.110.835
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.1390.94
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0830.968
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.7870.444
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.1950.418
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.4450.00767
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CDK6 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.305.30.507
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.109.10.519
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCDK6
Namecyclin-dependent kinase 6
Aliases PLSTIRE; MCPH12; cell division protein kinase 6; serine/threonine-protein kinase PLSTIRE
Chromosomal Location7q21-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CDK6. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolCDK6
Namecyclin-dependent kinase 6
Aliases PLSTIRE; MCPH12; cell division protein kinase 6; serine/threonine-protein kinase PLSTIRE
Chromosomal Location7q21-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CDK6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CDK6.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCDK6
Namecyclin-dependent kinase 6
Aliases PLSTIRE; MCPH12; cell division protein kinase 6; serine/threonine-protein kinase PLSTIRE
Chromosomal Location7q21-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CDK6. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCDK6
Namecyclin-dependent kinase 6
Aliases PLSTIRE; MCPH12; cell division protein kinase 6; serine/threonine-protein kinase PLSTIRE
Chromosomal Location7q21-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CDK6 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCDK6
Namecyclin-dependent kinase 6
Aliases PLSTIRE; MCPH12; cell division protein kinase 6; serine/threonine-protein kinase PLSTIRE
Chromosomal Location7q21-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CDK6 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCDK6
Namecyclin-dependent kinase 6
Aliases PLSTIRE; MCPH12; cell division protein kinase 6; serine/threonine-protein kinase PLSTIRE
Chromosomal Location7q21-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CDK6 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting CDK6.
ID Name Drug Type Targets #Targets
DB03496AlvocidibSmall MoleculeCDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, EGFR, PYGB, PYGL, ......12
DB07379(2S)-2-({6-[(3-amino-5-chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)-3-methylbutan-1-olSmall MoleculeCDK61
DB077953,7,3',4'-TETRAHYDROXYFLAVONESmall MoleculeCDK61
DB09073PalbociclibSmall MoleculeCDK4, CDK62
DB11730RibociclibSmall MoleculeCDK4, CDK62
DB12001AbemaciclibSmall MoleculeCDK4, CDK62