Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000913
UniProt IDQ9BQI3
Primary gene name(s)EIF2AK1
Synonym gene name(s)HRI, KIAA1369
Protein nameEukaryotic translation initiation factor 2-alpha kinase 1
Protein functionInhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser-48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions. In red blood cells, RBCs, controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. May also contain ER stress during acute heme-deficient conditions, By similarity. {ECO:0000250}.
Subcellular locationCytoplasm {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9BQI3
Gene Ontology
(Biological Process)
Complete annatation
acute inflammatory response [GO:0002526];
iron ion homeostasis [GO:0055072];
macrophage differentiation [GO:0030225];
negative regulation of cell proliferation [GO:0008285];
negative regulation of hemoglobin biosynthetic process [GO:0046986];
negative regulation of translational initiation by iron [GO:0045993];
phagocytosis [GO:0006909];
protein autophosphorylation [GO:0046777];
protoporphyrinogen IX metabolic process [GO:0046501];
regulation of eIF2 alpha phosphorylation by heme [GO:0010999];
response to external stimulus [GO:0009605];
response to stress [GO:0006950]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
eukaryotic translation initiation factor 2alpha kinase activity [GO:0004694];
heme binding [GO:0020037];
protein homodimerization activity [GO:0042803]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737]
Protein-protein interaction118002
Phylogenetic treeQ9BQI3
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. CD30.2384648283291330.4660006678034670.585687296959128
AZA vs. DISU0.08545321608238270.7353673910259260.974560663114398
AZA vs. IL70.005570820368088690.9768592647205310.999311006273513
AZA vs. SAHA-0.04108846768436610.8660828980477260.968584440051035
DISU vs. CD3-0.1653989980155710.6479616956909990.749376599727338
DISU vs. IL7-0.08905345254934170.7233990869689550.930462373158888
DISU vs. SAHA-0.1251143385474470.6676032883389390.898933766732129
DMSO vs. AZA-0.0210450230715580.8999060900294581
DMSO vs. CD3-0.2721062664207180.3944068819983050.509102876986073
DMSO vs. DISU-0.1087370042350680.6556028481020190.950002654032543
DMSO vs. IL70.03406107329282420.8495811763414680.966739578515353
DMSO vs. SAHA-0.0262225048137530.9113315365934130.979090218705398
HIV vs. Mock in Activation0.02250729378654780.9711234371003830.999983755607037
HIV vs. Mock in Latency0.01419194569646790.9313431289708290.999834320637052
IL7 vs. CD3-0.2254486775997930.4824501050832650.614238570311686
SAHA vs. CD3-0.3041204858954220.3890166702495330.505604244990121
SAHA vs. IL7-0.05017135000647870.8366458240529250.929546730508987
(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 -0.0576586 0.761483
(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
0.571 0.96 0.611 0.353 0.824
(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

not found

Protein Secondary Structure       (annotations from PDB)      top

not found

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)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)