Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000705
UniProt IDP68400
Primary gene name(s)CSNK2A1
Synonym gene name(s)CK2A1
Protein nameCasein kinase II subunit alpha
Protein functionCatalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint, SAC that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation. Plays an important role in the circadian clock function by phosphorylating ARNTL/BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry, PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621. Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue, PubMed:24962073. {ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:11704824, ECO:0000269|PubMed:16193064, ECO:0000269|PubMed:19188443, ECO:0000269|PubMed:20625391, ECO:0000269|PubMed:22406621, ECO:0000269|PubMed:24962073}.
Subcellular locationNucleus {ECO:0000269|PubMed:24962073}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P68400
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
chaperone-mediated protein folding [GO:0061077];
mitotic spindle checkpoint [GO:0071174];
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043154];
positive regulation of cell growth [GO:0030307];
positive regulation of cell proliferation [GO:0008284];
positive regulation of protein catabolic process [GO:0045732];
positive regulation of Wnt signaling pathway [GO:0030177];
protein folding [GO:0006457];
protein phosphorylation [GO:0006468];
regulation of signal transduction by p53 class mediator [GO:1901796];
regulation of transcription, DNA-templated [GO:0006355];
rhythmic process [GO:0048511];
signal transduction [GO:0007165];
transcription, DNA-templated [GO:0006351];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
Hsp90 protein binding [GO:0051879];
protein N-terminus binding [GO:0047485];
protein phosphatase regulator activity [GO:0019888];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
NuRD complex [GO:0016581];
plasma membrane [GO:0005886];
Sin3 complex [GO:0016580]
Protein-protein interaction107841
Phylogenetic treeP68400
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. CD31.086148067921420.001041979027969990.00377629516376208
AZA vs. DISU-0.02933716691437450.9076565970172880.994169411479968
AZA vs. IL70.1965318699410670.3068057963013760.999311006273513
AZA vs. SAHA-0.1397331251202270.5668200884578430.854786689998355
DISU vs. CD3-1.127597100524150.002172249512698120.00803545746120527
DISU vs. IL70.2165839718900570.3897591238101710.755901040967237
DISU vs. SAHA-0.1088411225924330.7085843992726950.913985614851178
DMSO vs. AZA-0.002918811756504690.9861068600070711
DMSO vs. CD3-1.099404400308470.0006869793421914180.00246078512148704
DMSO vs. DISU0.02488647362964260.9187176591672570.988899823982894
DMSO vs. IL70.206595189898240.2506372134347820.754614737872845
DMSO vs. SAHA-0.1432808291428510.5432775827412440.835145645384893
HIV vs. Mock in Activation0.2236725593731440.7192238465065220.999983755607037
HIV vs. Mock in Latency0.09618893592228250.5601914827802570.999834320637052
IL7 vs. CD3-0.8827437783423020.0064855796680070.0208431344524345
SAHA vs. CD3-1.249629404922160.0005020468996790320.00196311540689232
SAHA vs. IL7-0.3390258442125310.1640786588996040.385767605307813
(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 -0.00798615 0.971333
(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
1.008 0.978 1.037 1.087 0.903
(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
DB03127 Benzamidine experimental unknown unknown
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester experimental unknown unknown
DB04462 Tetrabromo-2-Benzotriazole experimental unknown unknown
DB02709 Resveratrol experimental, investigational unknown unknown
DB04720 S-METHYL-4,5,6,7-TETRABROMO-BENZIMIDAZOLE experimental unknown unknown
DB07715 3-METHYL-1,6,8-TRIHYDROXYANTHRAQUINONE experimental unknown unknown
DB07802 3,8-DIBROMO-7-HYDROXY-4-METHYL-2H-CHROMEN-2-ONE experimental unknown unknown
DB03035 1,8-Di-Hydroxy-4-Nitro-Anthraquinone experimental unknown unknown
DB01765 (5-Oxo-5,6-Dihydro-Indolo[1,2-a]Quinazolin-7-Yl)-Acetic Acid experimental unknown unknown
DB04719 DIMETHYL-(4,5,6,7-TETRABROMO-1H-BENZOIMIDAZOL-2-YL)-AMINE experimental unknown unknown
DB04721 N1,N2-ETHYLENE-2-METHYLAMINO-4,5,6,7-TETRABROMO-BENZIMIDAZOLE experimental unknown unknown
DB02170 1,8-Di-Hydroxy-4-Nitro-Xanthen-9-One experimental unknown unknown
DB03924 5,8-Di-Amino-1,4-Dihydroxy-Anthraquinone experimental unknown unknown
DB08338 19-(cyclopropylamino)-4,6,7,15-tetrahydro-5H-16,1-(azenometheno)-10,14-(metheno)pyrazolo[4,3-o][1,3,9]triazacyclohexadecin-8(9H)-one experimental unknown unknown
DB08340 N,N&,39;-DIPHENYLPYRAZOLO[1,5-A][1,3,5]TRIAZINE-2,4-DIAMINE experimental unknown unknown
DB08345 4-(2-(1H-IMIDAZOL-4-YL)ETHYLAMINO)-2-(PHENYLAMINO)PYRAZOLO[1,5-A][1,3,5]TRIAZINE-8-CARBONITRILE experimental unknown unknown
DB08354 2-(4-CHLOROBENZYLAMINO)-4-(PHENYLAMINO)PYRAZOLO[1,5-A][1,3,5]TRIAZINE-8-CARBONITRILE experimental unknown unknown
DB08360 2-(4-ETHYLPIPERAZIN-1-YL)-4-(PHENYLAMINO)PYRAZOLO[1,5-A][1,3,5]TRIAZINE-8-CARBONITRILE experimental unknown unknown
DB08362 N-(3-(8-CYANO-4-(PHENYLAMINO)PYRAZOLO[1,5-A][1,3,5]TRIAZIN-2-YLAMINO)PHENYL)ACETAMIDE experimental unknown unknown
DB08473 5,6-dichloro-1-beta-D-ribofuranosyl-1H-benzimidazole experimental unknown unknown
DB08660 1,2,5,8-tetrahydroxyanthracene-9,10-dione experimental unknown unknown
DB08846 Ellagic Acid investigational unknown inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1JWH X-ray 3.1Å A/B=1-337.
1NA7 X-ray 2.4Å A=1-329.
1PJK X-ray 2.5Å A=2-335.
2PVR X-ray 1.6Å A=2-335.
2ZJW X-ray 2.4Å A=1-335.
3AMY X-ray 2.3Å A=1-335.
3AT2 X-ray 1.6Å A=1-335.
3AT3 X-ray 2.6Å A=1-335.
3AT4 X-ray 2.2Å A=1-335.
3AXW X-ray 2.5Å A=1-335.
3BQC X-ray 1.5Å A=1-335.
3C13 X-ray 1.9Å A=1-335.
3FWQ X-ray 2.3Å A/B=1-335.
3H30 X-ray 1.5Å A/B=1-334.
3JUH X-ray 1.6Å A/B=1-335.
3MB6 X-ray 1.7Å A=1-331.
3MB7 X-ray 1.6Å A=1-331.
3NGA X-ray 2.7Å A/B=1-333.
3NSZ X-ray 1.3Å A=2-331.
3OWJ X-ray 1.8Å A=1-331.
3OWK X-ray 1.8Å A=1-331.
3OWL X-ray 2.1Å A=1-331.
3PE1 X-ray 1.6Å A=1-337.
3PE2 X-ray 1.9Å A=1-337.
3PE4 X-ray 1.9Å B/D=340-352.
3Q04 X-ray 1.8Å A=3-330.
3Q9W X-ray 1.7Å A=1-336.
3Q9X X-ray 2.2Å A/B=1-336.
3Q9Y X-ray 1.8Å A=1-336.
3Q9Z X-ray 2.2Å A/B=1-336.
3QA0 X-ray 2.5Å A/B=1-336.
3R0T X-ray 1.7Å A=1-337.
3RPS X-ray 2.3Å A/B=1-335.
3TAX X-ray 1.8Å B/D=340-352.
3U4U X-ray 2.2Å A=1-333.
3U87 X-ray 2.9Å A/B=1-325.
3U9C X-ray 3.2Å A/B=1-335.
3W8L X-ray 2.4Å A/B=1-335.
3WAR X-ray 1.0Å A=1-335.
3WIK X-ray 2.0Å A=1-335.
3WIL X-ray 2.9Å A=1-335.
3WOW X-ray 2.5Å A=1-335.
4DGL X-ray 3.0Å C/D=1-335.
4FBX X-ray 2.3Å A=1-335.
4GRB X-ray 2.1Å A=1-333.
4GUB X-ray 2.2Å A=1-333.
4GYW X-ray 1.7Å B/D=340-352.
4GYY X-ray 1.8Å B/D=340-352.
4GZ3 X-ray 1.9Å B/D=340-352.
4IB5 X-ray 2.2Å A/B/C=1-335.
4KWP X-ray 1.2Å A=1-336.
4MD7 X-ray 3.1Å E/F/G/H=1-391.
4MD8 X-ray 3.3Å E/F/G/H=1-391.
4MD9 X-ray 3.5Å E/F/G/H/K/L/M/P=1-336.
4NH1 X-ray 3.3Å A/B=1-335.
4RLL X-ray 1.8Å A=1-335.
4UB7 X-ray 2.1Å A=1-335.
4UBA X-ray 3.0Å A/B=1-335.
5B0X X-ray 2.3Å A=1-335.
5CLP X-ray 1.6Å A/B=2-329.
5CQU X-ray 2.3Å A=1-335.
5CQW X-ray 2.6Å A/B=1-335.
5CS6 X-ray 1.8Å A/B=2-329.
5CSH X-ray 1.5Å A/B=2-329.
5CSP X-ray 1.5Å A=2-329.
5CSV X-ray 1.3Å A=2-329.
5CU3 X-ray 1.7Å A/B=2-329.
5CU4 X-ray 1.5Å A=2-329.
5CU6 X-ray 1.3Å A=2-329.
5CVF X-ray 1.6Å A=2-329.
5CVG X-ray 1.2Å A=2-329.
5CVH X-ray 1.8Å A/B=2-329.
5H8B X-ray 2.5Å A/B=1-333.
5H8E X-ray 2.1Å A/B=1-333.
5H8G X-ray 2.0Å A=1-333.
5HGV X-ray 2.0Å B/D=340-352.

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

HIV Partner Interaction Type PubMed
Rev interacts with 22174317
reverse transcriptase stimulated by 9654140
Rev binds 11827166
matrix phosphorylated by 9151826
Rev activates 9654140
reverse transcriptase phosphorylated by 9654140
retropepsin phosphorylated by 10964683
Rev phosphorylated by 10984616
Vpu phosphorylated by 1541298
Rev modulated by 7794916

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03008 Ribosome biogenesis in eukaryotes - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa04520 Adherens junction - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)