Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000562
UniProt IDQ9NYV4
Primary gene name(s)CDK12
Synonym gene name(s)CRK7, CRKRS, KIAA0904
Protein nameCyclin-dependent kinase 12
Protein functionCyclin-dependent kinase that phosphorylates the C-terminal domain, CTD of the large subunit of RNA polymerase II, POLR2A, thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}.
Subcellular locationNucleus. Nucleus speckle. Note=Colocalized with nuclear speckles throughout interphase.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9NYV4
Gene Ontology
(Biological Process)
Complete annatation
mRNA processing [GO:0006397];
phosphorylation of RNA polymerase II C-terminal domain [GO:0070816];
protein autophosphorylation [GO:0046777];
regulation of MAP kinase activity [GO:0043405];
regulation of RNA splicing [GO:0043484];
RNA splicing [GO:0008380]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
cyclin binding [GO:0030332];
cyclin-dependent protein serine/threonine kinase activity [GO:0004693];
protein kinase activity [GO:0004672];
RNA polymerase II carboxy-terminal domain kinase activity [GO:0008353]
Gene Ontology
(Cellular Component)
Complete annatation
cyclin K-CDK12 complex [GO:0002944];
nuclear cyclin-dependent protein kinase holoenzyme complex [GO:0019908];
nuclear speck [GO:0016607];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction119715
Phylogenetic treeQ9NYV4
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD30.845632465513810.01049415892124820.0271439785929384
AZA vs. DISU0.2375934452669040.3473501177591590.885086688638042
AZA vs. IL70.1153401454924960.5484155196961870.999311006273513
AZA vs. SAHA-0.1448620369229470.5525732151513820.847322557662354
DISU vs. CD3-0.6209244189118870.08871899121626010.169757562020044
DISU vs. IL7-0.1313144309908160.6018143905684960.877129202262707
DISU vs. SAHA-0.3809749821670870.1912702839590640.559734844572243
DMSO vs. AZA0.04442876998496320.7908396177239791
DMSO vs. CD3-0.812608613925830.01184662935274060.0288132824021694
DMSO vs. DISU-0.1950126872312480.4237993828602210.87952097606939
DMSO vs. IL70.07819332844576560.6634895103059010.930888829953308
DMSO vs. SAHA-0.195881079726840.405917687730890.748145465548764
HIV vs. Mock in Activation0.2606593909853620.6755022031024830.999983755607037
HIV vs. Mock in Latency0.05224437769791380.7513401639603870.999834320637052
IL7 vs. CD3-0.7230144665258660.02564453856733220.0638803718105103
SAHA vs. CD3-1.01512706378050.004597117994333160.013297229975931
SAHA vs. IL7-0.2635202659192420.2791691229556790.52651672677373
(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) 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 -0.148896 0.318374
(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
1.034 1.07 0.952 0.948 1.052
(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

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
4CXA X-ray 3.1Å A/C=715-1052.
4NST X-ray 2.2Å A/C=714-1063.
4UN0 X-ray 3.1Å C/D=715-1038.
5ACB X-ray 2.7Å C/D=715-1052.

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
not found
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