CDK6 [The Human Chemical-Genetic Interaction Map Project]

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======= CDK6 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CDK6
  * **<color #00a2e8>Official Name</color>**: cyclin dependent kinase 6
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1021|1021]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q00534|Q00534]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CDK6&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CDK6|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/603368|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. Altered expression of this gene has been observed in multiple human cancers. A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly. [provided by RefSeq, Aug 2017]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000269|PubMed:12833137, ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273, ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663, ECO:0000269|PubMed:8114739}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase Tyr|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|cyclin D2-CDK6 complex|
|FBXO family protein binding|
|negative regulation of monocyte differentiation|
|dedifferentiation|
|cell dedifferentiation|
|lateral ventricle development|
|hematopoietic stem cell differentiation|
|type B pancreatic cell development|
|dentate gyrus development|
|regulation of monocyte differentiation|
|negative regulation of cellular senescence|
|type B pancreatic cell differentiation|
|glandular epithelial cell development|
|enteroendocrine cell differentiation|
|negative regulation of cell aging|
|ventricular system development|
|cyclin-dependent protein serine/threonine kinase activity|
|cyclin binding|
|cyclin-dependent protein kinase holoenzyme complex|
|astrocyte development|
|glandular epithelial cell differentiation|
|endocrine pancreas development|
|regulation of cellular senescence|
|negative regulation of osteoblast differentiation|
|negative regulation of myeloid leukocyte differentiation|
|regulation of erythrocyte differentiation|
|T cell differentiation in thymus|
|regulation of cell aging|
|columnar/cuboidal epithelial cell development|
|positive regulation of fibroblast proliferation|
|positive regulation of cell-matrix adhesion|
|astrocyte differentiation|
|regulation of hematopoietic stem cell differentiation|
|pancreas development|
|negative regulation of ossification|
|negative regulation of myeloid cell differentiation|
|hippocampus development|
|regulation of fibroblast proliferation|
|regulation of hematopoietic progenitor cell differentiation|
|hematopoietic progenitor cell differentiation|
|ruffle|
|columnar/cuboidal epithelial cell differentiation|
|negative regulation of leukocyte differentiation|
|negative regulation of G1/S transition of mitotic cell cycle|
|negative regulation of cell cycle G1/S phase transition|
|glial cell development|
|limbic system development|
|regulation of osteoblast differentiation|
|regulation of cell-matrix adhesion|
|regulation of myeloid leukocyte differentiation|
|regulation of stem cell differentiation|
|G1/S transition of mitotic cell cycle|
|cell cycle G1/S phase transition|
|endocrine system development|
|positive regulation of cell-substrate adhesion|
|negative regulation of epithelial cell proliferation|
|Notch signaling pathway|
|T cell differentiation|
|negative regulation of hemopoiesis|
|cell cycle arrest|
|regulation of G1/S transition of mitotic cell cycle|
|stem cell differentiation|
|regulation of cell cycle G1/S phase transition|
|glial cell differentiation|
|pallium development|
|regulation of ossification|
|epithelial cell development|
|regulation of cell-substrate adhesion|
|negative regulation of mitotic cell cycle phase transition|
|gliogenesis|
|regulation of myeloid cell differentiation|
|negative regulation of cell cycle phase transition|
|T cell activation|
|lymphocyte differentiation|
|telencephalon development|
|mitotic cell cycle phase transition|
|regulation of leukocyte differentiation|
|cell cycle phase transition|
|response to virus|
|negative regulation of mitotic cell cycle|
|negative regulation of cell cycle process|
|leukocyte differentiation|
|regulation of epithelial cell proliferation|
|lymphocyte activation|
|forebrain development|
|positive regulation of cell adhesion|
|regulation of mitotic cell cycle phase transition|
|negative regulation of immune system process|
|regulation of cell cycle phase transition|
|regulation of hemopoiesis|
|centrosome|
|cell division|
|hemopoiesis|
|negative regulation of cell cycle|
|mitotic cell cycle process|
|hematopoietic or lymphoid organ development|
|regulation of mitotic cell cycle|
|immune system development|
|negative regulation of cell population proliferation|
|epithelial cell differentiation|
|regulation of cell adhesion|
|mitotic cell cycle|
|negative regulation of cell differentiation|
|regulation of cellular response to stress|
|brain development|
|regulation of cell cycle process|
|head development|
|negative regulation of transcription by RNA polymerase II|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|leukocyte activation|
|negative regulation of developmental process|
|protein phosphorylation|
|central nervous system development|
|regulation of locomotion|
|regulation of cellular component movement|
|cell cycle process|
|cell activation|
|epithelium development|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|phosphorylation|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|negative regulation of RNA metabolic process|
|cell cycle|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|ATP binding|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|negative regulation of biosynthetic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|cell development|
|regulation of immune system process|
|negative regulation of gene expression|
|tissue development|
|regulation of cell differentiation|
|positive regulation of gene expression|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp71|KU-0063794 3.8μM R02 exp71]]|-2.85|
|[[:results:exp429|Rapamycin 0.001μM R08 exp429]]|-2.6|
|[[:results:exp82|Torin1 0.08μM R02 exp82]]|-2.49|
|[[:results:exp90|WYE-354 6μM R02 exp90]]|-2.34|
|[[:results:exp146|Quinacrine 2.5μM R03 exp146]]|-2.31|
|[[:results:exp155|UNC1999 2μM R03 exp155]]|-2.26|
|[[:results:exp20|Etoposide 10μM R00 exp20]]|-2.14|
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|-2.13|
|[[:results:exp417|Tubastatin-A 2.5μM R07 exp417]]|-2.03|
|[[:results:exp510|Nicotine 3000μM R08 exp510]]|-1.95|
|[[:results:exp124|GSK343 3μM R03 exp124]]|-1.87|
|[[:results:exp352|Dexamethasone 0.006 to 0.015μM on day4 R07 exp352]]|-1.72|
|[[:results:exp480|ETC-159 50μM R08 exp480]]|1.7|
|[[:results:exp359|FK-506 30μM R07 exp359]]|1.7|
|[[:results:exp259|6-Thio-2-deoxyguanosine 2μM R06 exp259]]|1.73|
|[[:results:exp80|RO-3307 4.7μM R02 exp80]]|1.76|
|[[:results:exp445|∆-9-Tetrahydrocannabinol 30μM R08 exp445]]|1.76|
|[[:results:exp380|NMS-873 0.07μM R07 exp380]]|1.88|
|[[:results:exp214|2-Deoxy-D-glucose 800μM R05 exp214]]|1.92|
|[[:results:exp349|Cytochalasin-B 5μM R07 exp349]]|2.35|
|[[:results:exp199|Etoposide 0.3μM R05 exp199]]|2.42|
|[[:results:exp116|AICAR 240μM R03 exp116]]|2.52|
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|2.53|
|[[:results:exp485|GSK626616 14μM R08 exp485]]|2.88|
|[[:results:exp211|AICAR 240μM R05 exp211]]|2.96|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|3.02|
|[[:results:exp505|ML-792 0.2μM R08 exp505]]|3.79|
|[[:results:exp35|TRAIL 5ng/ml R00 exp35]]|4.6|
|[[:results:exp36|TRAIL 50ng/ml R00 exp36]]|5.13|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:prim1|PRIM1]]|0.46|
|[[:human genes:l:lsm12|LSM12]]|0.455|
|[[:human genes:c:casp3|CASP3]]|0.455|
|[[:human genes:f:flcn|FLCN]]|0.405|
|[[:human genes:a:atxn2l|ATXN2L]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 138/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|6/28|
|blood|17/28|
|bone|3/26|
|breast|0/33|
|central nervous system|11/56|
|cervix|0/4|
|colorectal|1/17|
|esophagus|5/13|
|fibroblast|0/1|
|gastric|2/16|
|kidney|4/21|
|liver|1/20|
|lung|12/75|
|lymphocyte|6/16|
|ovary|0/26|
|pancreas|2/24|
|peripheral nervous system|6/16|
|plasma cell|9/15|
|prostate|0/1|
|skin|6/24|
|soft tissue|6/9|
|thyroid|0/2|
|upper aerodigestive|9/22|
|urinary tract|3/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 448
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 9.52 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CDK6 Expression in NALM6 Cells: 9.52'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>