Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000977
UniProt IDO75460
Primary gene name(s)ERN1
Synonym gene name(s)IRE1
Protein nameSerine/threonine-protein kinase/endoribonuclease IRE1
Protein functionSenses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto-activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis. {ECO:0000250|UniProtKB:Q9EQY0, ECO:0000269|PubMed:11175748, ECO:0000269|PubMed:12637535, ECO:0000269|PubMed:9637683}.
Subcellular locationEndoplasmic reticulum membrane {ECO:0000269|PubMed:9637683};
Single-pass type I membrane protein {ECO:0000269|PubMed:9637683}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O75460
Gene Ontology
(Biological Process)
Complete annatation
activation of JUN kinase activity [GO:0007257];
activation of signaling protein activity involved in unfolded protein response [GO:0006987];
cell cycle arrest [GO:0007050];
cellular response to glucose stimulus [GO:0071333];
cellular response to vascular endothelial growth factor stimulus [GO:0035924];
endothelial cell proliferation [GO:0001935];
insulin metabolic process [GO:1901142];
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress [GO:0070059];
IRE1-mediated unfolded protein response [GO:0036498];
mRNA catabolic process [GO:0006402];
mRNA cleavage [GO:0006379];
mRNA endonucleolytic cleavage involved in unfolded protein response [GO:0070055];
mRNA splicing, via endonucleolytic cleavage and ligation [GO:0070054];
peptidyl-serine autophosphorylation [GO:0036289];
peptidyl-serine trans-autophosphorylation [GO:1990579];
positive regulation of endoplasmic reticulum unfolded protein response [GO:1900103];
positive regulation of RNA splicing [GO:0033120];
positive regulation of vascular smooth muscle cell proliferation [GO:1904707];
protein autophosphorylation [GO:0046777];
protein phosphorylation [GO:0006468];
regulation of macroautophagy [GO:0016241];
regulation of transcription, DNA-templated [GO:0006355];
response to endoplasmic reticulum stress [GO:0034976];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
ADP binding [GO:0043531];
ATP binding [GO:0005524];
endoribonuclease activity [GO:0004521];
enzyme binding [GO:0019899];
Hsp70 protein binding [GO:0030544];
Hsp90 protein binding [GO:0051879];
identical protein binding [GO:0042802];
magnesium ion binding [GO:0000287];
protein homodimerization activity [GO:0042803];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
AIP1-IRE1 complex [GO:1990597];
cytoplasm [GO:0005737];
endoplasmic reticulum [GO:0005783];
endoplasmic reticulum membrane [GO:0005789];
integral component of endoplasmic reticulum membrane [GO:0030176];
Ire1 complex [GO:1990332];
IRE1-RACK1-PP2A complex [GO:1990630];
IRE1-TRAF2-ASK1 complex [GO:1990604];
mitochondrion [GO:0005739];
nuclear inner membrane [GO:0005637]
Protein-protein interaction108391
Phylogenetic treeO75460
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. CD3-2.009928222922573.22705606681239e-094.1857305541305e-08
AZA vs. DISU0.1300554829510140.6074790496453840.955602906116453
AZA vs. IL7-0.2542047960423060.1857820880267650.952505417553304
AZA vs. SAHA-0.1234268957030450.613132133238370.874185885581222
DISU vs. CD32.126973474168591.82873401977091e-082.66341416560644e-07
DISU vs. IL7-0.3930303006001540.1203780960039490.454190777048258
DISU vs. SAHA-0.2518990652559430.3868401650001450.753301049242351
DMSO vs. AZA0.04228688063867990.8002957703471661
DMSO vs. CD32.038599224463718.14568856810638e-101.0698761837709e-08
DMSO vs. DISU-0.09020721353655940.7115743285735890.962147565525893
DMSO vs. IL7-0.2887979208575520.1081809330376340.591522511984886
DMSO vs. SAHA-0.171898891090850.4658711058095030.792443844769281
HIV vs. Mock in Activation0.9533865118717510.1322805881524770.999983755607037
HIV vs. Mock in Latency0.1916467129637690.3822936025348480.999834320637052
IL7 vs. CD31.762648726120349.70951601342307e-081.18984987699452e-06
SAHA vs. CD31.861925813436833.39037199537096e-073.10029769236895e-06
SAHA vs. IL70.1264579491238340.6044313082003790.799908749187332
(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) TRUE
(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 -0.658218 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
unknown unknown unknown unknown unknown
(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
DB07382 N~2~-1H-benzimidazol-5-yl-N~4~-(3-cyclopropyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamine experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2HZ6 X-ray 3.1Å A=24-390.
3P23 X-ray 2.7Å A/B/C/D=547-977.
4U6R X-ray 2.5Å A=547-977.
4YZ9 X-ray 2.4Å A/B/C=562-966.
4YZC X-ray 2.4Å A/B=562-966.
4YZD X-ray 3.1Å A/B/C=562-966.
4Z7G X-ray 2.6Å A/B=562-977.
4Z7H X-ray 2.9Å A/B=562-977.
5HGI X-ray 2.5Å A=547-977.

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05010 Alzheimer's disease - Homo sapiens (human)