Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0004245
UniProt IDO14757
Primary gene name(s)CHEK1
Synonym gene name(s)CHK1
Protein nameSerine/threonine-protein kinase Chk1
Protein functionSerine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1, to form H3T11ph, which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest.; FUNCTION: Isoform 2: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.
Subcellular locationNucleus. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Nuclear export is mediated at least in part by XPO1/CRM1. Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O14757
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process involved in development [GO:1902742];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to mechanical stimulus [GO:0071260];
chromatin-mediated maintenance of transcription [GO:0048096];
DNA damage checkpoint [GO:0000077];
DNA damage induced protein phosphorylation [GO:0006975];
DNA repair [GO:0006281];
DNA replication [GO:0006260];
G2/M transition of mitotic cell cycle [GO:0000086];
G2 DNA damage checkpoint [GO:0031572];
inner cell mass cell proliferation [GO:0001833];
mitotic cell cycle checkpoint [GO:0007093];
negative regulation of mitotic nuclear division [GO:0045839];
nucleus organization [GO:0006997];
peptidyl-threonine phosphorylation [GO:0018107];
regulation of cell proliferation [GO:0042127];
regulation of double-strand break repair via homologous recombination [GO:0010569];
regulation of histone H3-K9 acetylation [GO:2000615];
regulation of mitotic centrosome separation [GO:0046602];
regulation of signal transduction by p53 class mediator [GO:1901796];
regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage [GO:0010767];
replicative senescence [GO:0090399]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
histone kinase activity, H3-T11 specific [GO:0035402];
kinase activity [GO:0016301];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
centrosome [GO:0005813];
chromatin [GO:0000785];
condensed nuclear chromosome [GO:0000794];
cytosol [GO:0005829];
extracellular space [GO:0005615];
intracellular membrane-bounded organelle [GO:0043231];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
replication fork [GO:0005657]
Protein-protein interaction107536
Phylogenetic treeO14757
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. CD32.939427056157560.001159654656716640.00413492192714292
AZA vs. DISU0.01488766118987560.9544047691872830.996649735504266
AZA vs. IL71.167121948643150.005553659902070020.23122326268554
AZA vs. SAHA-0.01308300656935330.9587085456658410.990779256780515
DISU vs. CD3-2.935751461935380.001110139575283830.00454241149778188
DISU vs. IL71.142903952030670.006645375847463390.0895255057198486
DISU vs. SAHA-0.02686262641708830.9281141150328240.983106113465755
DMSO vs. AZA-0.1351935765810960.5264535755042141
DMSO vs. CD3-3.085960177609340.0006573040232658030.00236613742186364
DMSO vs. DISU-0.1521226806627590.5454566767329580.922272808496102
DMSO vs. IL71.308862423617060.001087310909518750.0598219414634858
DMSO vs. SAHA0.1152974637076890.6367890574795920.883107187667305
HIV vs. Mock in Activation-0.3186422301371440.8534781596958920.999983755607037
HIV vs. Mock in Latency-0.05471372287009950.7824751836670210.999834320637052
IL7 vs. CD3-1.763841132846660.05224868265016550.113922232545341
SAHA vs. CD3-2.976619136408680.001033404084930470.00368775741413738
SAHA vs. IL7-1.182168166617560.003342923845700340.0288774980229725
(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 0.740591 0.000305467
(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
0.912 0.815 0.641 0.572 0.968
(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
DB06852 4-[(3S)-1-AZABICYCLO[2.2.2]OCT-3-YLAMINO]-3-(1H-BENZIMIDAZOL-2-YL)-6-CHLOROQUINOLIN-2(1H)-ONE experimental unknown unknown
DB06876 N-{5-[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]-1H-PYRROLO[2,3-B]PYRIDIN-3-YL}NICOTINAMIDE experimental unknown unknown
DB07025 3-(5-{[4-(AMINOMETHYL)PIPERIDIN-1-YL]METHYL}-1H-INDOL-2-YL)QUINOLIN-2(1H)-ONE experimental unknown unknown
DB07034 2,2&,39;-{[9-(HYDROXYIMINO)-9H-FLUORENE-2,7-DIYL]BIS(OXY)}DIACETIC ACID experimental unknown unknown
DB07037 (2S)-1-AMINO-3-[(5-NITROQUINOLIN-8-YL)AMINO]PROPAN-2-OL experimental unknown unknown
DB07038 2-(cyclohexylamino)benzoic acid experimental unknown unknown
DB07075 3-(5-{[4-(AMINOMETHYL)PIPERIDIN-1-YL]METHYL}-1H-INDOL-2-YL)-1H-INDAZOLE-6-CARBONITRILE experimental unknown unknown
DB07078 (3Z)-6-(4-HYDROXY-3-METHOXYPHENYL)-3-(1H-PYRROL-2-YLMETHYLENE)-1,3-DIHYDRO-2H-INDOL-2-ONE experimental unknown unknown
DB07158 5-ETHYL-3-METHYL-1,5-DIHYDRO-4H-PYRAZOLO[4,3-C]QUINOLIN-4-ONE experimental unknown unknown
DB07213 (5-{3-[5-(PIPERIDIN-1-YLMETHYL)-1H-INDOL-2-YL]-1H-INDAZOL-6-YL}-2H-1,2,3-TRIAZOL-4-YL)METHANOL experimental unknown unknown
DB07228 1-(5-CHLORO-2-METHOXYPHENYL)-3-{6-[2-(DIMETHYLAMINO)-1-METHYLETHOXY]PYRAZIN-2-YL}UREA experimental unknown unknown
DB07243 (3-ENDO)-8-METHYL-8-AZABICYCLO[3.2.1]OCT-3-YL 1H-PYRROLO[2,3-B]PYRIDINE-3-CARBOXYLATE experimental unknown unknown
DB07311 18-CHLORO-11,12,13,14-TETRAHYDRO-1H,10H-8,4-(AZENO)-9,15,1,3,6-BENZODIOXATRIAZACYCLOHEPTADECIN-2-ONE experimental unknown unknown
DB07314 1-(5-CHLORO-2,4-DIMETHOXYPHENYL)-3-(5-CYANOPYRAZIN-2-YL)UREA experimental unknown unknown
DB07320 4-(6-{[(4-METHYLCYCLOHEXYL)AMINO]METHYL}-1,4-DIHYDROINDENO[1,2-C]PYRAZOL-3-YL)BENZOIC ACID experimental unknown unknown
DB07336 4-[3-(1H-BENZIMIDAZOL-2-YL)-1H-INDAZOL-6-YL]-2-METHOXYPHENOL experimental unknown unknown
DB07647 (2R)-1-[(5,6-DIPHENYL-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)AMINO]PROPAN-2-OL experimental unknown unknown
DB07648 (2R)-3-{[(4Z)-5,6-DIPHENYL-6,7-DIHYDRO-4H-PYRROLO[2,3-D]PYRIMIDIN-4-YLIDENE]AMINO}PROPANE-1,2-DIOL experimental unknown unknown
DB07653 N-(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)GLYCINE experimental unknown unknown
DB07654 (5,6-DIPHENYL-FURO[2,3-D]PYRIMIDIN-4-YLAMINO)-ACETIC experimental unknown unknown
DB07655 3-AMINO-3-BENZYL-[4.3.0]BICYCLO-1,6-DIAZANONAN-2-ONE experimental unknown unknown
DB07959 3-(1H-BENZIMIDAZOL-2-YL)-1H-INDAZOLE experimental unknown unknown
DB08392 2-[5,6-BIS-(4-METHOXY-PHENYL)-FURO[2,3-D]PYRIMIDIN-4-YLAMINO]-ETHANOL experimental unknown unknown
DB08393 2-[(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHANOL experimental unknown unknown
DB08683 REL-(9R,12S)-9,10,11,12-TETRAHYDRO-9,12-EPOXY-1H-DIINDOLO[1,2,3-FG:3&,39;,2&,39;,1&,39;-KL]PYRROLO[3,4-I][1,6]BENZODIAZOCINE-1,3(2H)-DIONE experimental unknown unknown
DB08774 1-[(2S)-4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)morpholin-2-yl]methanamine experimental unknown unknown
DB08776 N-(4-OXO-5,6,7,8-TETRAHYDRO-4H-[1,3]THIAZOLO[5,4-C]AZEPIN-2-YL)ACETAMIDE experimental unknown unknown
DB08777 5,6,7,8-TETRAHYDRO[1]BENZOTHIENO[2,3-D]PYRIMIDIN-4(3H)-ONE experimental unknown unknown
DB08778 [4-amino-2-(tert-butylamino)-1,3-thiazol-5-yl](phenyl)methanone experimental unknown unknown
DB08779 2-(methylsulfanyl)-5-(thiophen-2-ylmethyl)-1H-imidazol-4-ol experimental unknown unknown
DB08780 6-MORPHOLIN-4-YL-9H-PURINE experimental unknown unknown
DB08781 1-[(2S)-4-(5-BROMO-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1IA8 X-ray 1.7Å A=1-289.
1NVQ X-ray 2.0Å A=1-289.
1NVR X-ray 1.8Å A=1-289.
1NVS X-ray 1.8Å A=1-289.
1ZLT X-ray 1.7Å A=1-289.
1ZYS X-ray 1.7Å A=1-273.
2AYP X-ray 2.9Å A=1-269.
2BR1 X-ray 2.0Å A=1-289.
2BRB X-ray 2.1Å A=1-289.
2BRG X-ray 2.1Å A=1-289.
2BRH X-ray 2.1Å A=1-289.
2BRM X-ray 2.2Å A=1-289.
2BRN X-ray 2.8Å A=1-289.
2BRO X-ray 2.2Å A=1-289.
2C3J X-ray 2.1Å A=1-289.
2C3K X-ray 2.6Å A=1-289.
2C3L X-ray 2.3Å A=1-289.
2CGU X-ray 2.5Å A=1-289.
2CGV X-ray 2.6Å A=1-289.
2CGW X-ray 2.2Å A=1-289.
2CGX X-ray 2.2Å A=1-289.
2E9N X-ray 2.5Å A=2-270.
2E9O X-ray 2.1Å A=2-270.
2E9P X-ray 2.6Å A=2-270.
2E9U X-ray 2.0Å A=2-270.
2E9V X-ray 2.0Å A/B=2-269.
2GDO X-ray 3.0Å A=1-289.
2GHG X-ray 3.5Å A=2-270.
2HOG X-ray 1.9Å A=2-307.
2HXL X-ray 1.8Å A=2-307.
2HXQ X-ray 2.0Å A=2-307.
2HY0 X-ray 1.7Å A=2-307.
2QHM X-ray 2.0Å A=1-307.
2QHN X-ray 1.7Å A=1-307.
2R0U X-ray 1.9Å A=1-307.
2WMQ X-ray 2.4Å A=1-289.
2WMR X-ray 2.4Å A=1-289.
2WMS X-ray 2.7Å A=1-289.
2WMT X-ray 2.5Å A=1-289.
2WMU X-ray 2.6Å A=1-289.
2WMV X-ray 2.0Å A=1-289.
2WMW X-ray 2.4Å A=1-289.
2WMX X-ray 2.4Å A=1-289.
2X8D X-ray 1.9Å A=1-289.
2X8E X-ray 2.5Å A=1-276.
2X8I X-ray 1.9Å A=1-289.
2XEY X-ray 2.7Å A=1-289.
2XEZ X-ray 2.2Å A=1-289.
2XF0 X-ray 2.4Å A=1-289.
2YDI X-ray 1.6Å A=1-289.
2YDJ X-ray 1.8Å A/B=1-276.
2YDK X-ray 1.9Å A=1-276.
2YER X-ray 1.8Å A=1-276.
2YEX X-ray 1.3Å A=1-276.
2YM3 X-ray 2.0Å A=1-289.
2YM4 X-ray 2.3Å A=1-289.
2YM5 X-ray 2.0Å A=1-289.
2YM6 X-ray 2.0Å A=1-289.
2YM7 X-ray 1.8Å A=1-289.
2YM8 X-ray 2.0Å A=1-289.
2YWP X-ray 2.9Å A=2-270.
3F9N X-ray 1.9Å A=2-307.
3JVR X-ray 1.7Å A=2-272.
3JVS X-ray 1.9Å A=2-272.
3NLB X-ray 1.9Å A=1-289.
3OT3 X-ray 1.4Å A=2-274.
3OT8 X-ray 1.6Å A=2-274.
3PA3 X-ray 1.4Å A=2-274.
3PA4 X-ray 1.5Å A=2-274.
3PA5 X-ray 1.7Å A=2-274.
3TKH X-ray 1.7Å A=1-307.
3TKI X-ray 1.6Å A=1-307.
3U9N X-ray 1.8Å A=2-274.
4FSM X-ray 2.3Å A=2-280.
4FSN X-ray 2.1Å A=4-280.
4FSQ X-ray 2.4Å A=2-280.
4FSR X-ray 2.5Å A=2-280.
4FST X-ray 1.9Å A=2-270.
4FSU X-ray 2.1Å A=2-280.
4FSW X-ray 2.3Å A=2-280.
4FSY X-ray 2.3Å A=2-280.
4FSZ X-ray 2.3Å A=2-280.
4FT0 X-ray 2.3Å A=2-280.
4FT3 X-ray 2.5Å A=2-280.
4FT5 X-ray 2.4Å A=2-280.
4FT7 X-ray 2.2Å A=2-280.
4FT9 X-ray 2.2Å A=2-280.
4FTA X-ray 2.4Å A=2-280.
4FTC X-ray 2.0Å A=2-280.
4FTI X-ray 2.2Å A=2-280.
4FTJ X-ray 2.2Å A=2-280.
4FTK X-ray 2.3Å A=2-280.
4FTL X-ray 2.5Å A=2-280.
4FTM X-ray 1.9Å A=2-280.
4FTN X-ray 2.0Å A=2-280.
4FTO X-ray 2.1Å A=2-280.
4FTQ X-ray 2.0Å A=2-280.
4FTR X-ray 2.2Å A=2-280.
4FTT X-ray 2.3Å A=2-280.
4FTU X-ray 2.1Å A=2-280.
4GH2 X-ray 2.0Å A=2-280.
4HYH X-ray 1.7Å A=1-289.
4HYI X-ray 1.4Å A=1-289.
4JIK X-ray 1.9Å A=2-274.
4QYE X-ray 2.0Å A=1-289.
4QYF X-ray 2.1Å A=1-289.
4QYG X-ray 1.7Å A/B=1-289.
4QYH X-ray 1.9Å A/B=1-289.
4RVK X-ray 1.8Å A=1-289.
4RVL X-ray 1.8Å A=1-289.
4RVM X-ray 1.8Å A=1-289.
5DLS X-ray 2.1Å A=1-289.
5F4N X-ray 1.9Å A=1-273.

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

HIV Partner Interaction Type PubMed
Vpr induces phosphorylation of 17210576
Vpr activates 12738771

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)
hsa05203 Viral carcinogenesis - Homo sapiens (human)