Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0004189
UniProt IDP50613
Primary gene name(s)CDK7
Synonym gene name(s)CAK, CAK1, CDKN7, MO15, STK1
Protein nameCyclin-dependent kinase 7
Protein functionSerine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases, CDKs are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition, but not complex formation. CDK7 is the catalytic subunit of the CDK-activating kinase, CAK complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain, CTD of its large subunit, POLR2A, allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:16327805, ECO:0000269|PubMed:17373709, ECO:0000269|PubMed:17386261, ECO:0000269|PubMed:17901130, ECO:0000269|PubMed:19015234, ECO:0000269|PubMed:19071173, ECO:0000269|PubMed:19136461, ECO:0000269|PubMed:19450536, ECO:0000269|PubMed:19667075, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:9372954, ECO:0000269|PubMed:9840937}.
Subcellular locationNucleus. Cytoplasm. Cytoplasm, perinuclear region. Note=Colocalizes with PRKCI in the cytoplasm and nucleus. Translocates from the nucleus to cytoplasm and perinuclear region in response to DNA-bound peptides.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P50613
Gene Ontology
(Biological Process)
Complete annatation
7-methylguanosine mRNA capping [GO:0006370];
androgen receptor signaling pathway [GO:0030521];
cell cycle arrest [GO:0007050];
cell division [GO:0051301];
cell proliferation [GO:0008283];
G1/S transition of mitotic cell cycle [GO:0000082];
G2/M transition of mitotic cell cycle [GO:0000086];
nucleotide-excision repair, preincision complex assembly [GO:0006294];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0000079];
snRNA transcription from RNA polymerase II promoter [GO:0042795];
termination of RNA polymerase I transcription [GO:0006363];
transcription-coupled nucleotide-excision repair [GO:0006283];
transcription elongation from RNA polymerase II promoter [GO:0006368];
transcription elongation from RNA polymerase I promoter [GO:0006362];
transcription from RNA polymerase II promoter [GO:0006366];
transcription initiation from RNA polymerase II promoter [GO:0006367];
transcription initiation from RNA polymerase I promoter [GO:0006361]
Gene Ontology
(Molecular Function)
Complete annatation
androgen receptor binding [GO:0050681];
ATP binding [GO:0005524];
cyclin-dependent protein serine/threonine kinase activity [GO:0004693];
DNA-dependent ATPase activity [GO:0008094];
kinase activity [GO:0016301];
protein C-terminus binding [GO:0008022];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674];
RNA polymerase II carboxy-terminal domain kinase activity [GO:0008353];
transcription coactivator activity [GO:0003713]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
holo TFIIH complex [GO:0005675];
mitochondrion [GO:0005739];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471]
Protein-protein interaction107457
Phylogenetic treeP50613
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. CD31.269534035479730.0001417523871301010.000657179938119003
AZA vs. DISU0.1938276609836870.4485029273589380.918669250520452
AZA vs. IL7-0.01476449123033930.9401476561476990.999311006273513
AZA vs. SAHA-0.1548084588116440.5322234385161630.838744313078707
DISU vs. CD3-1.088982582153450.00303084616823590.0106521275681949
DISU vs. IL7-0.2173392416743910.3931650625380970.758786215682428
DISU vs. SAHA-0.3468899480440540.2383039504712590.616629694761562
DMSO vs. AZA-0.1244139440285840.4720795503951021
DMSO vs. CD3-1.404310421473131.74695367435307e-059.49075265204796e-05
DMSO vs. DISU-0.3198554755709070.1951575845765450.713270904924328
DMSO vs. IL70.1166909057193980.5266303712685280.894044407376504
DMSO vs. SAHA-0.0371770326501440.8765934636508880.969358567504663
HIV vs. Mock in Activation-0.09241262563722430.8820487484747480.999983755607037
HIV vs. Mock in Latency0.05557243966766480.742518162366560.999834320637052
IL7 vs. CD3-1.275959085445369.69504297926305e-050.000567067841778936
SAHA vs. CD3-1.448410016138646.33543389558788e-050.000320708729615416
SAHA vs. IL7-0.1429552306948230.5629334400834370.771844522086386
(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 unknown
(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) unknown
(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 0.392587 0.032068
(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
1.074 1.111 0.944 0.941 0.92
(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
DB02482 Phosphonothreonine experimental unknown unknown
DB03496 Flavopiridol experimental, investigational unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1LG3 Model - A=1-307.
1PA8 Model - A=181-346.
1UA2 X-ray 3.0Å A/B/C/D=1-346.
2HIC Model - B=13-311.

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

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03022 Basal transcription factors - Homo sapiens (human)
hsa03420 Nucleotide excision repair - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)