Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0005187
UniProt IDO14964
Primary gene name(s)HGS
Synonym gene name(s)HRS
Protein nameHepatocyte growth factor-regulated tyrosine kinase substrate
Protein functionInvolved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. May concentrate ubiquitinated receptors within clathrin-coated regions. Involved in down-regulation of receptor tyrosine kinase via multivesicular body, MVBs when complexed with STAM, ESCRT-0 complex. The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes. May contribute to the efficient recruitment of SMADs to the activin receptor complex. Involved in receptor recycling via its association with the CART complex, a multiprotein complex required for efficient transferrin receptor recycling but not for EGFR degradation.
Subcellular locationCytoplasm. Early endosome membrane;
Peripheral membrane protein;
Cytoplasmic side. Endosome, multivesicular body membrane {ECO:0000250};
Peripheral membrane protein {ECO:0000250}. Note=Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments. {ECO:0000269|PubMed:16159959}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O14964
Gene Ontology
(Biological Process)
Complete annatation
autophagy [GO:0006914];
endosomal transport [GO:0016197];
membrane invagination [GO:0010324];
multivesicular body assembly [GO:0036258];
negative regulation of cell proliferation [GO:0008285];
negative regulation of epidermal growth factor receptor signaling pathway [GO:0042059];
negative regulation of JAK-STAT cascade [GO:0046426];
positive regulation of exosomal secretion [GO:1903543];
positive regulation of gene expression [GO:0010628];
protein localization to membrane [GO:0072657];
protein targeting to lysosome [GO:0006622];
regulation of MAP kinase activity [GO:0043405];
regulation of protein catabolic process [GO:0042176];
signal transduction [GO:0007165]
Gene Ontology
(Molecular Function)
Complete annatation
metal ion binding [GO:0046872];
protein domain specific binding [GO:0019904]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
early endosome [GO:0005769];
early endosome membrane [GO:0031901];
endosome [GO:0005768];
ESCRT-0 complex [GO:0033565];
extracellular exosome [GO:0070062];
intracellular membrane-bounded organelle [GO:0043231];
multivesicular body membrane [GO:0032585]
Protein-protein interaction114593
Phylogenetic treeO14964
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. CD30.2374344493768540.4720216744984040.591380771241891
AZA vs. DISU0.5332188942741290.0355032469389130.43731969643412
AZA vs. IL7-0.1551228041212220.4431413363780010.999311006273513
AZA vs. SAHA-0.08945102608261460.7142215915869820.919478714799058
DISU vs. CD30.2821114660181360.4422604950211130.573609192041814
DISU vs. IL7-0.6978856001614280.005801907914058770.0825129828343735
DISU vs. SAHA-0.6193210517320660.03457255843237380.225172149201207
DMSO vs. AZA0.04669463814613950.7808222707484611
DMSO vs. CD3-0.2024261070145560.5310544978762750.636969427588064
DMSO vs. DISU-0.4884255002580170.04565734214974240.426304923294063
DMSO vs. IL7-0.1942080228275160.2808280988076920.771688587226751
DMSO vs. SAHA-0.1409591631314450.5508061305163880.838941200974091
HIV vs. Mock in Activation0.4486241186339440.4731986337240410.999983755607037
HIV vs. Mock in Latency0.09924994683226110.5484972192995930.999834320637052
IL7 vs. CD3-0.3879770573567680.2328944267873870.362234825607912
SAHA vs. CD3-0.349723572201460.324012093650110.439066833136153
SAHA vs. IL70.06330369250943950.7954173478369650.911172665194498
(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) unknown
(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 -0.698855 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
0.979 0.956 0.941 0.834 1.026
(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
DB04272 Citric Acid nutraceutical, vet_approved unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2D3G X-ray 1.7Å P=257-277.
3F1I X-ray 2.3Å H=404-501.
3OBQ X-ray 1.4Å B=346-354.
3ZYQ X-ray 1.4Å A=1-225.
4AVX X-ray 1.6Å A=1-225.

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

HIV Partner Interaction Type PubMed
Vpu interacts with 21304933
Pr55(Gag) inhibited by 17182674
Nef co-localizes with 24489825
Vpu requires 26317613
Vpu cooperates with 21304933
HIV-1 virus replication enhanced by expression of human gene 18187620

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04144 Endocytosis - Homo sapiens (human)
hsa04145 Phagosome - Homo sapiens (human)