Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003840
UniProt IDQ13315
Primary gene name(s)ATM
Synonym gene name(s)unknown
Protein nameSerine-protein kinase ATM
Protein functionSerine/threonine protein kinase which activates checkpoint signaling upon double strand breaks, DSBs, apoptosis and genotoxic stresses such as ionizing ultraviolet A light, UVA, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks, DSBs, thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor, BCR expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin, NBN, TERF1, RAD9 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response. {ECO:0000269|PubMed:10973490, ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702, ECO:0000269|PubMed:19965871}.
Subcellular locationNucleus {ECO:0000269|PubMed:9050866, ECO:0000269|PubMed:9150358}. Cytoplasmic vesicle {ECO:0000269|PubMed:9050866, ECO:0000269|PubMed:9150358}. Note=Primarily nuclear. Found also in endocytic vesicles in association with beta-adaptin. {ECO:0000269|PubMed:9050866, ECO:0000269|PubMed:9150358}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13315
Gene Ontology
(Biological Process)
Complete annatation
brain development [GO:0007420];
cell cycle arrest [GO:0007050];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to gamma radiation [GO:0071480];
cellular response to nitrosative stress [GO:0071500];
cellular response to X-ray [GO:0071481];
determination of adult lifespan [GO:0008340];
DNA damage induced protein phosphorylation [GO:0006975];
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977];
DNA double-strand break processing [GO:0000729];
DNA repair [GO:0006281];
DNA replication [GO:0006260];
DNA synthesis involved in DNA repair [GO:0000731];
double-strand break repair via homologous recombination [GO:0000724];
double-strand break repair via nonhomologous end joining [GO:0006303];
establishment of macromolecular complex localization to telomere [GO:0097695];
establishment of RNA localization to telomere [GO:0097694];
heart development [GO:0007507];
histone mRNA catabolic process [GO:0071044];
histone phosphorylation [GO:0016572];
intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630];
lipoprotein catabolic process [GO:0042159];
meiotic telomere clustering [GO:0045141];
mitotic spindle assembly checkpoint [GO:0007094];
negative regulation of B cell proliferation [GO:0030889];
negative regulation of telomere capping [GO:1904354];
negative regulation of TORC1 signaling [GO:1904262];
neuron apoptotic process [GO:0051402];
oocyte development [GO:0048599];
peptidyl-serine autophosphorylation [GO:0036289];
peptidyl-serine phosphorylation [GO:0018105];
positive regulation of apoptotic process [GO:0043065];
positive regulation of DNA damage response, signal transduction by p53 class mediator [GO:0043517];
positive regulation of histone phosphorylation [GO:0033129];
positive regulation of neuron apoptotic process [GO:0043525];
positive regulation of telomerase catalytic core complex assembly [GO:1904884];
positive regulation of telomere maintenance via telomerase [GO:0032212];
positive regulation of telomere maintenance via telomere lengthening [GO:1904358];
pre-B cell allelic exclusion [GO:0002331];
protein autophosphorylation [GO:0046777];
protein phosphorylation [GO:0006468];
reciprocal meiotic recombination [GO:0007131];
regulation of apoptotic process [GO:0042981];
regulation of autophagy [GO:0010506];
regulation of cellular response to heat [GO:1900034];
regulation of signal transduction by p53 class mediator [GO:1901796];
replicative senescence [GO:0090399];
response to hypoxia [GO:0001666];
response to ionizing radiation [GO:0010212];
signal transduction [GO:0007165];
signal transduction involved in mitotic G2 DNA damage checkpoint [GO:0072434];
somitogenesis [GO:0001756];
strand displacement [GO:0000732];
telomere maintenance via telomerase [GO:0007004];
V(DJ recombination [GO:0033151]
Gene Ontology
(Molecular Function)
Complete annatation
1-phosphatidylinositol-3-kinase activity [GO:0016303];
ATP binding [GO:0005524];
DNA binding [GO:0003677];
DNA-dependent protein kinase activity [GO:0004677];
protein complex binding [GO:0032403];
protein dimerization activity [GO:0046983];
protein N-terminus binding [GO:0047485];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasmic, membrane-bounded vesicle [GO:0016023];
DNA repair complex [GO:1990391];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
spindle [GO:0005819]
Protein-protein interaction106962
Phylogenetic treeQ13315
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. CD3-3.3676819623537500
AZA vs. DISU-0.2587112895809990.3056193208218780.864889484929148
AZA vs. IL7-0.4395109931662250.02195619104040770.474134194200666
AZA vs. SAHA-0.5038597829739410.03932689283672520.23422109151355
DISU vs. CD33.096042104286393.66373598126302e-151.98658835185463e-13
DISU vs. IL7-0.1894111754315810.4513624640056860.797079038530056
DISU vs. SAHA-0.244928640135630.4001152180717880.7601470147223
DMSO vs. AZA-0.004368524014696520.9790835111927551
DMSO vs. CD33.3506014983732200
DMSO vs. DISU0.2521750217432860.3006597068520680.807887568985919
DMSO vs. IL7-0.4277757431755250.01708454005994240.27225099514126
DMSO vs. SAHA-0.5069233403529310.03200404108180150.192773702791274
HIV vs. Mock in Activation0.1616777772908680.8283209737632110.999983755607037
HIV vs. Mock in Latency0.05648171237866610.7313638376688930.999834320637052
IL7 vs. CD32.937147708543641.11022302462516e-154.92187989711029e-14
SAHA vs. CD32.838069932581231.7608137170555e-136.07218826453692e-12
SAHA vs. IL7-0.06913708101013090.7764817683261250.901400552618252
(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 -0.906 1.66E-05 2.68E-04
Infected vs. Bystander -1.139 5.77E-07 1.12E-05
(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 1.17075 0.000580925
(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
0.967 1.051 1.104 1.303 1.579
(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
208442_s_at 1.40 No downregulated in CD8+ cells
212672_at 1.49 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00201 Caffeine approved unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

not found

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

HIV Partner Interaction Type PubMed
Rev stimulated by 16474151
integrase interacts with 11158303
23432899
Envelope surface glycoprotein gp160; precursor interacts with 19023333
19177012
Envelope surface glycoprotein gp160; precursor induces phosphorylation of 19023333
Tat upregulates 19050264
Envelope surface glycoprotein gp160; precursor cooperates with 19164952
19177012
Vpr activates 16983346
18514189
18577246
19275579
19275588
20012529
21519849
23202519
24744753
24795708
Vif downregulates 21874023
21934670

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa03440 Homologous recombination - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
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