Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001145
UniProt IDQ92616
Primary gene name(s)GCN1
Synonym gene name(s)GCN1L1, KIAA0219
Protein nameeIF-2-alpha kinase activator GCN1
Protein functionActs as a positive activator of the EIF2AK4/GCN2 protein kinase activity in response to amino acid starvation. Forms a complex with EIF2AK4/GCN2 on translating ribosomes; during this process, GCN1 seems to act as a chaperone to facilitate delivery of uncharged tRNAs that enter the A site of ribosomes to the tRNA-binding domain of EIF2AK4/GCN2, and hence stimulating EIF2AK4/GCN2 kinase activity. Participates in the repression of global protein synthesis and in gene-specific mRNA translation activation, such as the transcriptional activator ATF4, by promoting the EIF2AK4/GCN2-mediated phosphorylation of eukaryotic translation initiation factor 2, eIF-2-alpha/EIF2S1 on 'Ser-52', and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. {ECO:0000250|UniProtKB:E9PVA8, ECO:0000250|UniProtKB:P33892}.
Subcellular locationCytoplasm {ECO:0000250|UniProtKB:E9PVA8}. Note=Associates with ribosomes in undifferentiated neuroblastoma cells and increases after neuronal differentiation. {ECO:0000250|UniProtKB:E9PVA8}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q92616
Gene Ontology
(Biological Process)
Complete annatation
cellular response to amino acid starvation [GO:0034198];
cellular response to leucine starvation [GO:1990253];
positive regulation of kinase activity [GO:0033674];
positive regulation of transcription from RNA polymerase II promoter in response to stress [GO:0036003];
regulation of translation [GO:0006417]
Gene Ontology
(Molecular Function)
Complete annatation
unknown
Gene Ontology
(Cellular Component)
Complete annatation
unknown
Protein-protein interaction116181
Phylogenetic treeQ92616
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. CD30.7519072710271470.0223862868805160.0510757063068631
AZA vs. DISU0.1089439194738210.6660497478586460.962297595817978
AZA vs. IL70.1849700842507310.3348232550746050.999311006273513
AZA vs. SAHA-0.2674662735870120.2727524091745880.6471698120412
DISU vs. CD3-0.6559158900135630.0715740948964180.143414582808534
DISU vs. IL70.06685151470819260.7902865219114940.952138955641538
DISU vs. SAHA-0.3741104579021590.1994290725778030.570280935590532
DMSO vs. AZA0.1236478424494410.4591819834116621
DMSO vs. CD3-0.6418293412414880.04601931331907570.0898730820782831
DMSO vs. DISU0.01224931539927090.9598831584225460.994105021699463
DMSO vs. IL70.06898309431733950.7004288622982150.937788846060647
DMSO vs. SAHA-0.3963951923858210.09255429693958290.356847918727528
HIV vs. Mock in Activation0.2647431848461920.6702873516740220.999983755607037
HIV vs. Mock in Latency-0.03301678108514950.8409814597115510.999834320637052
IL7 vs. CD3-0.560470594312550.08228829500050660.162880035527595
SAHA vs. CD3-1.043193735196820.003599359259046970.0107368060241168
SAHA vs. IL7-0.455337943492090.06160740686496790.210701374199887
(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 0.0497171 0.788799
(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
0.994 0.996 1.004 1.039 0.98
(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
not found
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