Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002000
UniProt IDP22736
Primary gene name(s)NR4A1
Synonym gene name(s)GFRP1, HMR, NAK1
Protein nameNuclear receptor subfamily 4 group A member 1
Protein functionOrphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element, NBRE 5'-AAAAGGTCA-3', By similarity. May inhibit NF-kappa-B transactivation of IL2. Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation. {ECO:0000250, ECO:0000269|PubMed:15466594, ECO:0000269|PubMed:22983157}.
Subcellular locationCytoplasm. Nucleus.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P22736
Gene Ontology
(Biological Process)
Complete annatation
cell migration involved in sprouting angiogenesis [GO:0002042];
cellular response to corticotropin-releasing hormone stimulus [GO:0071376];
cellular response to fibroblast growth factor stimulus [GO:0044344];
cellular response to vascular endothelial growth factor stimulus [GO:0035924];
endothelial cell chemotaxis [GO:0035767];
fat cell differentiation [GO:0045444];
negative regulation of cell cycle [GO:0045786];
positive regulation of endothelial cell proliferation [GO:0001938];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
regulation of type B pancreatic cell proliferation [GO:0061469];
signal transduction [GO:0007165];
transcription initiation from RNA polymerase II promoter [GO:0006367]
Gene Ontology
(Molecular Function)
Complete annatation
DNA binding [GO:0003677];
protein heterodimerization activity [GO:0046982];
RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding [GO:0004879];
sequence-specific DNA binding [GO:0043565];
steroid hormone receptor activity [GO:0003707];
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding [GO:0001077];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
nuclear membrane [GO:0031965];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction109407
Phylogenetic treeP22736
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. CD36.4657477644585500
AZA vs. DISU0.93543491598150.00288585650254980.138548566832274
AZA vs. IL7unknownunknownunknown
AZA vs. SAHA1.570778575134194.51672125358904e-050.00208849865572396
DISU vs. CD3-5.5492421837009700
DISU vs. IL7-1.076039885773970.0004408946063210180.0158627355376834
DISU vs. SAHA0.6401138006346270.0616883841562720.314302108728592
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3-6.2145307326231500
DMSO vs. DISU-0.6699378143367060.02197355170802570.306043349014401
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHA1.301158957418671.61824085241902e-050.000823936077256994
HIV vs. Mock in Activation0.5160245628359960.4127423516293860.999983755607037
HIV vs. Mock in Latency-0.5774541145022190.1642401570518130.999834320637052
IL7 vs. CD3-6.5976154906283400
SAHA vs. CD3-4.9177750247880200
SAHA vs. IL71.707594141519288.33728499349817e-060.00026513973416032
(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 0.85 2.29E-09 1.94E-07
Infected vs. Bystander 0.923 4.78E-10 3.12E-08
(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 0.4135 0.00532573
(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

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2QW4 X-ray 2.8Å A/B/C/D=347-598.
3V3E X-ray 2.0Å A/B=351-598.
3V3Q X-ray 2.2Å A/B=351-598.
4JGV X-ray 3.0Å A/B=351-598.
4KZI X-ray 2.4Å A/B=351-598.
4KZJ X-ray 2.1Å A/B=351-598.
4KZM X-ray 2.3Å A/B=351-598.
4RE8 X-ray 2.1Å A/B=351-598.
4REE X-ray 2.3Å A/B=351-598.
4REF X-ray 2.1Å A/B=351-598.
4RZE X-ray 2.4Å A/B=351-598.
4RZF X-ray 1.9Å A/B=351-598.
4RZG X-ray 2.7Å A/B=351-598.
4WHF X-ray 2.2Å A/B=351-598.
4WHG X-ray 2.1Å A/B=351-598.

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

HIV Partner Interaction Type PubMed
Vpr downregulates 14751250
Tat upregulates 25613138

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04925 Aldosterone synthesis and secretion - Homo sapiens (human)