Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000600
UniProt IDO96017
Primary gene name(s)CHEK2
Synonym gene name(s)CDS1, CHK2, RAD53
Protein nameSerine/threonine-protein kinase Chk2
Protein functionSerine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair, including BRCA2 through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition, PubMed:25361978. {ECO:0000250|UniProtKB:Q9Z265, ECO:0000269|PubMed:10097108, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:17101782, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:17715138, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:20364141, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25619829, ECO:0000269|PubMed:9836640, ECO:0000269|PubMed:9889122}.
Subcellular locationIsoform 2: Nucleus. Note=Isoform 10 is present throughout the cell.;
SUBCELLULAR LOCATION: Isoform 4: Nucleus.;
SUBCELLULAR LOCATION: Isoform 7: Nucleus.;
SUBCELLULAR LOCATION: Isoform 9: Nucleus.;
SUBCELLULAR LOCATION: Isoform 12: Nucleus.;
SUBCELLULAR LOCATION: Nucleus, PML body. Nucleus, nucleoplasm. Note=Recruited into PML bodies together with TP53.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O96017
Gene Ontology
(Biological Process)
Complete annatation
cell division [GO:0051301];
cellular protein catabolic process [GO:0044257];
cellular response to bisphenol A [GO:1903926];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to drug [GO:0035690];
cellular response to gamma radiation [GO:0071480];
DNA damage checkpoint [GO:0000077];
DNA damage induced protein phosphorylation [GO:0006975];
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977];
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator [GO:0006978];
double-strand break repair [GO:0006302];
G2/M transition of mitotic cell cycle [GO:0000086];
intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630];
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:0042771];
mitotic spindle assembly [GO:0090307];
negative regulation of cell cycle arrest [GO:0071157];
negative regulation of DNA damage checkpoint [GO:2000002];
peptidyl-serine phosphorylation [GO:0018105];
positive regulation of anoikis [GO:2000210];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of transcription, DNA-templated [GO:0045893];
protein autophosphorylation [GO:0046777];
protein phosphorylation [GO:0006468];
protein stabilization [GO:0050821];
regulation of protein catabolic process [GO:0042176];
regulation of signal transduction by p53 class mediator [GO:1901796];
regulation of transcription, DNA-templated [GO:0006355];
replicative cell aging [GO:0001302];
replicative senescence [GO:0090399];
signal transduction in response to DNA damage [GO:0042770];
signal transduction involved in intra-S DNA damage checkpoint [GO:0072428];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
identical protein binding [GO:0042802];
metal ion binding [GO:0046872];
protein homodimerization activity [GO:0042803];
protein kinase binding [GO:0019901];
protein serine/threonine kinase activity [GO:0004674];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
Golgi apparatus [GO:0005794];
nucleoplasm [GO:0005654];
PML body [GO:0016605]
Protein-protein interaction116369
Phylogenetic treeO96017
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. CD30.6527788032132030.2165651806061940.324492534257537
AZA vs. DISU0.5488605703660250.1820540142931880.76836786777268
AZA vs. IL70.3907142189261930.05561352968007880.686142885704394
AZA vs. SAHA0.6852162044950230.006937161563003060.0765525427530806
DISU vs. CD3-0.1190385040270490.8479586817463830.897180400691021
DISU vs. IL7-0.1658585192696770.7022027840671690.923741138299926
DISU vs. SAHA0.1391520728067760.762283968912330.933369685352729
DMSO vs. AZA0.03622286890828070.8422538736074461
DMSO vs. CD3-0.6322655733566190.23216926042120.335729497815836
DMSO vs. DISU-0.5150270918627310.2173732931221370.729493704699699
DMSO vs. IL70.3620002181476230.05807922275227810.467701055378083
DMSO vs. SAHA0.6440246907922770.008564328619342980.0811779852969295
HIV vs. Mock in Activation0.1264987462484730.9122489155112020.999983755607037
HIV vs. Mock in Latency0.04322763098090840.8079675533077460.999834320637052
IL7 vs. CD3-0.2534197696622640.6386831578304720.748299357790805
SAHA vs. CD30.008185780386604640.9888395633164760.992197364616772
SAHA vs. IL70.2925596125413270.2582445043761180.503398119612777
(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 -0.0737965 0.782573
(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
1.006 1.056 0.997 1.064 1.027
(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
DB05149 XL844 investigational unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1GXC X-ray 2.7Å A/D/G/J=64-212.
2CN5 X-ray 2.2Å A=210-531.
2CN8 X-ray 2.7Å A=210-531.
2W0J X-ray 2.0Å A=210-531.
2W7X X-ray 2.0Å A=210-531.
2WTC X-ray 3.0Å A=210-531.
2WTD X-ray 2.7Å A=210-531.
2WTI X-ray 2.5Å A=210-531.
2WTJ X-ray 2.1Å A=210-531.
2XBJ X-ray 2.3Å A=210-531.
2XK9 X-ray 2.3Å A=210-531.
2XM8 X-ray 3.4Å A=210-531.
2XM9 X-ray 2.5Å A=210-531.
2YCF X-ray 1.7Å A=210-530.
2YCQ X-ray 2.0Å A=210-531.
2YCR X-ray 2.2Å A=210-531.
2YCS X-ray 2.3Å A=210-531.
2YIQ X-ray 1.8Å A=210-531.
2YIR X-ray 2.1Å A=210-531.
2YIT X-ray 2.2Å A=210-531.
3I6U X-ray 3.0Å A/B=84-502.
3I6W X-ray 3.2Å A/B/C/D/E/F/G/H=70-512.
3VA4 X-ray 1.5Å C=63-73.
4A9R X-ray 2.8Å A=210-531.
4A9S X-ray 2.6Å A=210-531.
4A9T X-ray 2.7Å A=210-531.
4A9U X-ray 2.4Å A=210-531.
4BDA X-ray 2.6Å A=210-531.
4BDB X-ray 2.5Å A=210-531.
4BDC X-ray 3.0Å A=210-531.
4BDD X-ray 2.6Å A=210-531.
4BDE X-ray 2.5Å A=210-531.
4BDF X-ray 2.7Å A=210-531.
4BDG X-ray 2.8Å A=210-531.
4BDH X-ray 2.7Å A=210-531.
4BDI X-ray 2.3Å A=210-531.
4BDJ X-ray 3.0Å A=210-531.
4BDK X-ray 3.3Å A=210-531.

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

HIV Partner Interaction Type PubMed
Vpr induces phosphorylation of 16983346
Envelope surface glycoprotein gp160; precursor cooperates with 19164952

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)
hsa05166 HTLV-I infection - Homo sapiens (human)