Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000568
UniProt IDP11802
Primary gene name(s)CDK4
Synonym gene name(s)unknown
Protein nameCyclin-dependent kinase 4
Protein functionSer/Thr-kinase component of cyclin D-CDK4, DC complexes that phosphorylate and inhibit members of the retinoblastoma, RB protein family including RB1 and regulate the cell-cycle during G(1/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1 phase. Hypophosphorylates RB1 in early G(1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. {ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:9003781}.
Subcellular locationCytoplasm. Nucleus. Membrane. Note=Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G(1 phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G(1 to S phase. Also present in nucleoli and heterochromatin lumps. Colocalizes with RB1 after release into the nucleus.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P11802
Gene Ontology
(Biological Process)
Complete annatation
animal organ regeneration [GO:0031100];
cell division [GO:0051301];
circadian rhythm [GO:0007623];
G1/S transition of mitotic cell cycle [GO:0000082];
lens development in camera-type eye [GO:0002088];
negative regulation of cell cycle arrest [GO:0071157];
positive regulation of apoptotic process [GO:0043065];
positive regulation of cell cycle [GO:0045787];
positive regulation of cell proliferation [GO:0008284];
positive regulation of cell size [GO:0045793];
positive regulation of fibroblast proliferation [GO:0048146];
positive regulation of G2/M transition of mitotic cell cycle [GO:0010971];
positive regulation of translation [GO:0045727];
protein phosphorylation [GO:0006468];
regulation of gene expression [GO:0010468];
response to drug [GO:0042493];
response to hyperoxia [GO:0055093];
response to lead ion [GO:0010288];
response to testosterone [GO:0033574];
response to toxic substance [GO:0009636];
signal transduction [GO:0007165]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
cyclin binding [GO:0030332];
cyclin-dependent protein serine/threonine kinase activity [GO:0004693];
cyclin-dependent protein serine/threonine kinase regulator activity [GO:0016538]
Gene Ontology
(Cellular Component)
Complete annatation
bicellular tight junction [GO:0005923];
chromatin [GO:0000785];
cyclin-dependent protein kinase holoenzyme complex [GO:0000307];
cytosol [GO:0005829];
nuclear membrane [GO:0031965];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
transcription factor complex [GO:0005667]
Protein-protein interaction107454
Phylogenetic treeP11802
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. CD32.145218598772133.26250471083256e-105.18696951494392e-09
AZA vs. DISU-0.2470676075473510.3306311779505320.879082798222567
AZA vs. IL70.4446966393614210.02160771191327980.470654684492582
AZA vs. SAHA0.001338699094074340.9956491707279690.998870616987704
DISU vs. CD3-2.404763396135652.86843548913396e-106.53154026634521e-09
DISU vs. IL70.6825913745229080.007110985017756870.0937046321177314
DISU vs. SAHA0.2502227671400930.3925017824471730.75661891280309
DMSO vs. AZA0.05392699521074690.7497184259621071
DMSO vs. CD3-2.105679050670782.49421816533868e-103.64455835701525e-09
DMSO vs. DISU0.2982320928748670.2234564761920750.736085960261148
DMSO vs. IL70.3986279487929250.02761075580488360.337030075917911
DMSO vs. SAHA-0.0577276526508750.8075572277787180.946665555824309
HIV vs. Mock in Activation-0.07888904710107710.8990984950354970.999983755607037
HIV vs. Mock in Latency-0.1166439020331410.4851321170626050.999834320637052
IL7 vs. CD3-1.693438776486412.83426057401392e-073.13438037901089e-06
SAHA vs. CD3-2.167997958355664.534189690375e-096.51598442896406e-08
SAHA vs. IL7-0.4461573804437470.0685675760288420.226614260262829
(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
unknown unknown

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 -1.012053675
(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 0.256257 0.0923086
(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
0.757 0.711 0.337 0.352 0.93
(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
DB02733 Purvalanol experimental unknown unknown
DB09073 Palbociclib approved yes Inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1LD2 Model - A=1-303.
2W96 X-ray 2.3Å B=1-303.
2W99 X-ray 2.8Å B=1-303.
2W9F X-ray 2.8Å B=1-303.
2W9Z X-ray 2.4Å B=1-303.
3G33 X-ray 3.0Å A/C=1-303.
5FWK EM 3.9Å K=1-303.
5FWL EM 9.0Å K=1-303.
5FWM EM 8.0Å K=1-303.

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

HIV Partner Interaction Type PubMed
Tat requires 10639311
Tat interacts with 15050687

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01522 Endocrine resistance - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04530 Tight junction - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05214 Glioma - Homo sapiens (human)
hsa05218 Melanoma - Homo sapiens (human)
hsa05219 Bladder cancer - 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)