Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000118
UniProt IDP27695
Primary gene name(s)APEX1
Synonym gene name(s)APE, APE1, APEX, APX, HAP1, REF1
Protein nameDNA-(apurinic or apyrimidinic site lyase
Protein functionMultifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic, AP endodeoxyribonuclease in the DNA base excision repair, BER pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions, such as phosphoglycolate blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate, dRp excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination, CSR. On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone, PTH expression by binding to negative calcium response elements, nCaREs. Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant, CRD. In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA. {ECO:0000269|PubMed:10023679, ECO:0000269|PubMed:11118054, ECO:0000269|PubMed:11452037, ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:11832948, ECO:0000269|PubMed:12524539, ECO:0000269|PubMed:16617147, ECO:0000269|PubMed:1719477, ECO:0000269|PubMed:18179823, ECO:0000269|PubMed:18439621, ECO:0000269|PubMed:18579163, ECO:0000269|PubMed:18809583, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:19401441, ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:20699270, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:8355688, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:8932375, ECO:0000269|PubMed:9108029, ECO:0000269|PubMed:9207062, ECO:0000269|PubMed:9560228, ECO:0000269|PubMed:9804799}.
Subcellular locationNucleus. Nucleus, nucleolus. Nucleus speckle. Endoplasmic reticulum. Cytoplasm. Note=Detected in the cytoplasm of B-cells stimulated to switch, By similarity. Colocalized with SIRT1 in the nucleus. Colocalized with YBX1 in nuclear speckles after genotoxic stress. Together with OGG1 is recruited to nuclear speckles in UVA-irradiated cells. Colocalized with nucleolin and NPM1 in the nucleolus. Its nucleolar localization is cell cycle dependent and requires active rRNA transcription. Colocalized with calreticulin in the endoplasmic reticulum. Translocation from the nucleus to the cytoplasm is stimulated in presence of nitric oxide, NO and function in a CRM1-dependent manner, possibly as a consequence of demasking a nuclear export signal, amino acid position 64-80. S-nitrosylation at Cys-93 and Cys-310 regulates its nuclear-cytosolic shuttling. Ubiquitinated form is localized predominantly in the cytoplasm. {ECO:0000250}.;
SUBCELLULAR LOCATION: DNA-(apurinic or apyrimidinic site lyase, mitochondrial: Mitochondrion. Note=The cleaved APEX2 is only detected in mitochondria, By similarity. Translocation from the cytoplasm to the mitochondria is mediated by ROS signaling and cleavage mediated by granzyme A. Tom20-dependent translocated mitochondrial APEX1 level is significantly increased after genotoxic stress. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P27695
Gene Ontology
(Biological Process)
Complete annatation
aging [GO:0007568];
base-excision repair [GO:0006284];
base-excision repair, base-free sugar-phosphate removal [GO:0006286];
cell redox homeostasis [GO:0045454];
cellular response to cAMP [GO:0071320];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to peptide hormone stimulus [GO:0071375];
DNA demethylation [GO:0080111];
DNA recombination [GO:0006310];
DNA repair [GO:0006281];
negative regulation of smooth muscle cell migration [GO:0014912];
positive regulation of DNA repair [GO:0045739];
positive regulation of G1/S transition of mitotic cell cycle [GO:1900087];
regulation of mRNA stability [GO:0043488];
regulation of transcription, DNA-templated [GO:0006355];
response to drug [GO:0042493];
telomere maintenance [GO:0000723];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
3'-5' exonuclease activity [GO:0008408];
chromatin DNA binding [GO:0031490];
damaged DNA binding [GO:0003684];
DNA-(apurinic or apyrimidinic site lyase activity [GO:0003906];
DNA binding [GO:0003677];
double-stranded DNA 3'-5' exodeoxyribonuclease activity [GO:0008311];
double-stranded DNA exodeoxyribonuclease activity [GO:0008309];
double-stranded telomeric DNA binding [GO:0003691];
endodeoxyribonuclease activity [GO:0004520];
endonuclease activity [GO:0004519];
metal ion binding [GO:0046872];
oxidoreductase activity [GO:0016491];
phosphodiesterase I activity [GO:0004528];
phosphoric diester hydrolase activity [GO:0008081];
poly(A RNA binding [GO:0044822];
RNA-DNA hybrid ribonuclease activity [GO:0004523];
site-specific endodeoxyribonuclease activity, specific for altered base [GO:0016890];
transcription coactivator activity [GO:0003713];
transcription corepressor activity [GO:0003714];
uracil DNA N-glycosylase activity [GO:0004844]
Gene Ontology
(Cellular Component)
Complete annatation
centrosome [GO:0005813];
cytoplasm [GO:0005737];
endoplasmic reticulum [GO:0005783];
mitochondrion [GO:0005739];
nuclear chromosome, telomeric region [GO:0000784];
nuclear speck [GO:0016607];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
ribosome [GO:0005840];
transcription factor complex [GO:0005667]
Protein-protein interaction106825
Phylogenetic treeP27695
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. CD31.032808235732580.001781541949788520.00600165406061972
AZA vs. DISU-0.2553770702713670.3126597354127320.868081173655893
AZA vs. IL70.2599575209416970.1761661077011540.942900166334986
AZA vs. SAHA-0.05140819284387290.8328905946327550.959845248930506
DISU vs. CD3-1.300076140297850.0004071923493499390.00191454069684996
DISU vs. IL70.5061536866572370.04474726166910650.279980468876379
DISU vs. SAHA0.2052890229085790.4808419000488170.811434633281613
DMSO vs. AZA0.04520962388289130.7869808597192831
DMSO vs. CD3-1.000554750783120.001914769028602990.00600582873535375
DMSO vs. DISU0.2982440792894720.221455115125810.733159745634375
DMSO vs. IL70.2222130946136850.2160292573029290.724804783238115
DMSO vs. SAHA-0.1028166432981180.6623487899708260.893649775454289
HIV vs. Mock in Activation-0.09409442703114410.8797493541842420.999983755607037
HIV vs. Mock in Latency-0.128281612253910.4368667138128050.999834320637052
IL7 vs. CD3-0.7650889249764560.0176673354126220.0474180460602656
SAHA vs. CD3-1.108700160116960.001903852619804520.00621785201240996
SAHA vs. IL7-0.3143495823518640.1967056207872570.428216132231294
(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 -0.413598 0.00108419
(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
1.01 1.07 0.973 0.967 1.017
(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
DB04967 Lucanthone approved, investigational yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1BIX X-ray 2.2Å A=32-318.
1CQG NMR - B=59-71.
1CQH NMR - B=59-71.
1DE8 X-ray 2.9Å A/B=43-318.
1DE9 X-ray 3.0Å A/B=43-318.
1DEW X-ray 2.6Å A/B=40-318.
1E9N X-ray 2.2Å A/B=2-318.
1HD7 X-ray 1.9Å A=2-318.
2ISI X-ray 2.7Å A/B/C=2-318.
2O3H X-ray 1.9Å A=40-318.
3U8U X-ray 2.1Å A/B/C/D/E/F=1-318.
4IEM X-ray 2.3Å A/B/C/D=2-318.
4LND X-ray 1.9Å A/B/C=39-318.
4QH9 X-ray 2.1Å A=38-318.
4QHD X-ray 1.6Å A=38-318.
4QHE X-ray 1.4Å A=38-318.
5CFG X-ray 1.8Å A=44-318.
5DFF X-ray 1.5Å A/B=43-318.
5DFH X-ray 1.9Å A/B=43-318.
5DFI X-ray 1.6Å A/B=43-318.
5DFJ X-ray 1.8Å A/B=43-318.
5DG0 X-ray 1.8Å A/B=43-318.

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

HIV Partner Interaction Type PubMed
Rev interacts with 22174317
HIV-1 virus replication enhanced by expression of human gene 19266025

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03410 Base excision repair - Homo sapiens (human)