Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000570
UniProt IDQ00534
Primary gene name(s)CDK6
Synonym gene name(s)CDKN6
Protein nameCyclin-dependent kinase 6
Protein functionSerine/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}.
Subcellular locationCytoplasm. Nucleus. Cell projection, ruffle. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:23918663}. 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. {ECO:0000250|UniProtKB:Q64261, ECO:0000269|PubMed:23918663}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q00534
Gene Ontology
(Biological Process)
Complete annatation
astrocyte development [GO:0014002];
cell cycle arrest [GO:0007050];
cell dedifferentiation [GO:0043697];
cell division [GO:0051301];
cellular response to phorbol 13-acetate 12-myristate [GO:1904628];
dentate gyrus development [GO:0021542];
G1/S transition of mitotic cell cycle [GO:0000082];
generation of neurons [GO:0048699];
gliogenesis [GO:0042063];
lateral ventricle development [GO:0021670];
negative regulation of cell cycle [GO:0045786];
negative regulation of cell differentiation [GO:0045596];
negative regulation of cell proliferation [GO:0008285];
negative regulation of cellular senescence [GO:2000773];
negative regulation of epithelial cell proliferation [GO:0050680];
negative regulation of monocyte differentiation [GO:0045656];
negative regulation of myeloid cell differentiation [GO:0045638];
negative regulation of osteoblast differentiation [GO:0045668];
positive regulation of cell-matrix adhesion [GO:0001954];
positive regulation of fibroblast proliferation [GO:0048146];
protein phosphorylation [GO:0006468];
regulation of cell motility [GO:2000145];
regulation of erythrocyte differentiation [GO:0045646];
regulation of gene expression [GO:0010468];
response to virus [GO:0009615];
type B pancreatic cell development [GO:0003323]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
cyclin binding [GO:0030332];
cyclin-dependent protein serine/threonine kinase activity [GO:0004693]
Gene Ontology
(Cellular Component)
Complete annatation
centrosome [GO:0005813];
cyclin-dependent protein kinase holoenzyme complex [GO:0000307];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
ruffle [GO:0001726]
Protein-protein interaction107456
Phylogenetic treeQ00534
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.6915864831543250.03567413324708110.0751895589847583
AZA vs. DISU-0.1139592398557490.6515403582087940.960057478314726
AZA vs. IL70.8132516493002972.45279518149566e-050.00586840980487049
AZA vs. SAHA-0.2108311586776820.3864791207503590.748911976628219
DISU vs. CD3-0.8175504606351890.02497249133011060.0616399761437837
DISU vs. IL70.9178753660925890.0002903730554899560.0117527554542074
DISU vs. SAHA-0.09508467410887510.7438421955888260.926558039167447
DMSO vs. AZA-0.04188057518362860.8077250865192541
DMSO vs. CD3-0.7392993357536050.02148244097809490.0475581151116826
DMSO vs. DISU0.07194771999394770.767496464276690.969965025068444
DMSO vs. IL70.8616020856816641.78086210278483e-060.000547887677540435
DMSO vs. SAHA-0.1764997479207370.4531986490689570.78360972403089
HIV vs. Mock in Activation0.5736746301609670.3602214276491220.999983755607037
HIV vs. Mock in Latency0.1106169418307050.8024930312174830.999834320637052
IL7 vs. CD30.127953079269430.6901841105002330.789372873326506
SAHA vs. CD3-0.9262347516717670.00955225343093480.0246367378408673
SAHA vs. IL7-1.026700717582652.9096306232157e-050.000728282775335824
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
-0.3194 0.03183

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change -1.288840684
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.701636 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.917 1.358 1.264 1.147 1.402
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB03496 Flavopiridol experimental, investigational unknown unknown
DB07379 (2S)-2-({6-[(3-amino-5-chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)-3-methylbutan-1-ol experimental unknown unknown
DB07795 3,7,3&,39;,4&,39;-TETRAHYDROXYFLAVONE experimental unknown unknown
DB09073 Palbociclib approved yes Inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1BI7 X-ray 3.4Å A=1-326.
1BI8 X-ray 2.8Å A/C=1-326.
1BLX X-ray 1.9Å A=1-326.
1G3N X-ray 2.9Å A/E=1-326.
1JOW X-ray 3.1Å B=1-308.
1XO2 X-ray 2.9Å B=1-308.
2EUF X-ray 3.0Å B=1-308.
2F2C X-ray 2.8Å B=1-308.
3NUP X-ray 2.6Å A=1-301.
3NUX X-ray 2.7Å A=1-301.
4AUA X-ray 2.3Å A=1-301.
4EZ5 X-ray 2.7Å A=1-301.
4TTH X-ray 2.9Å B=1-326.
5L2I X-ray 2.7Å A=1-301.
5L2S X-ray 2.2Å A=1-301.
5L2T X-ray 2.3Å A=1-301.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Tat downregulates 23166591

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04110 Cell cycle - Homo sapiens (human)
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05214 Glioma - Homo sapiens (human)
hsa05218 Melanoma - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)
hsa05223 Non-small cell lung cancer - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)