Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001216
UniProt IDP62993
Primary gene name(s)GRB2
Synonym gene name(s)ASH
Protein nameGrowth factor receptor-bound protein 2
Protein functionAdapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.; FUNCTION: Isoform 2 does not bind to phosphorylated epidermal growth factor receptor, EGFR but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.
Subcellular locationNucleus {ECO:0000269|PubMed:21179510}. Cytoplasm {ECO:0000269|PubMed:21179510}. Endosome {ECO:0000269|PubMed:21179510}. Golgi apparatus {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P62993
Gene Ontology
(Biological Process)
Complete annatation
aging [GO:0007568];
anatomical structure formation involved in morphogenesis [GO:0048646];
axon guidance [GO:0007411];
branching involved in labyrinthine layer morphogenesis [GO:0060670];
cell-cell signaling [GO:0007267];
cellular response to ionizing radiation [GO:0071479];
epidermal growth factor receptor signaling pathway [GO:0007173];
ERBB2 signaling pathway [GO:0038128];
Fc-epsilon receptor signaling pathway [GO:0038095];
Fc-gamma receptor signaling pathway involved in phagocytosis [GO:0038096];
fibroblast growth factor receptor signaling pathway [GO:0008543];
insulin receptor signaling pathway [GO:0008286];
leukocyte migration [GO:0050900];
MAPK cascade [GO:0000165];
negative regulation of epidermal growth factor receptor signaling pathway [GO:0042059];
phosphatidylinositol-mediated signaling [GO:0048015];
positive regulation of actin filament polymerization [GO:0030838];
positive regulation of reactive oxygen species metabolic process [GO:2000379];
protein heterooligomerization [GO:0051291];
Ras protein signal transduction [GO:0007265];
receptor internalization [GO:0031623];
regulation of MAPK cascade [GO:0043408];
regulation of phosphatidylinositol 3-kinase signaling [GO:0014066];
signal transduction in response to DNA damage [GO:0042770];
T cell costimulation [GO:0031295];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
1-phosphatidylinositol-3-kinase activity [GO:0016303];
ephrin receptor binding [GO:0046875];
epidermal growth factor receptor binding [GO:0005154];
identical protein binding [GO:0042802];
insulin receptor substrate binding [GO:0043560];
neurotrophin TRKA receptor binding [GO:0005168];
phosphatidylinositol-4,5-bisphosphate 3-kinase activity [GO:0046934];
poly(A RNA binding [GO:0044822];
protein kinase binding [GO:0019901];
Ras guanyl-nucleotide exchange factor activity [GO:0005088];
SH3/SH2 adaptor activity [GO:0005070];
SH3 domain binding [GO:0017124]
Gene Ontology
(Cellular Component)
Complete annatation
cell-cell junction [GO:0005911];
COP9 signalosome [GO:0008180];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endosome [GO:0005768];
extracellular exosome [GO:0070062];
Golgi apparatus [GO:0005794];
Grb2-EGFR complex [GO:0070436];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
vesicle membrane [GO:0012506]
Protein-protein interaction109142
Phylogenetic treeP62993
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. CD30.02086660073520070.9490951492885530.967191486820627
AZA vs. DISU-0.0496029530393420.8442636431138570.987545094943509
AZA vs. IL7-0.03845865682668430.8410998547584480.999311006273513
AZA vs. SAHA-0.1165445357421680.6332444454366290.884359080062927
DISU vs. CD3-0.08306947564202490.8184371879578750.876278298975567
DISU vs. IL70.001785187203491670.9943350188497290.999618797576393
DISU vs. SAHA-0.06485591118717970.8243423196384510.954821755916372
DMSO vs. AZA0.007222598869844240.965512465344341
DMSO vs. CD3-0.02649858293896750.933835752926450.95423154160191
DMSO vs. DISU0.05465540357587850.8224371759880260.980295078677667
DMSO vs. IL7-0.03825715475442870.8311204391719740.963051812112721
DMSO vs. SAHA-0.1290199729462160.5847243032562010.857364138361632
HIV vs. Mock in Activation0.1467913894904330.813274519448850.999983755607037
HIV vs. Mock in Latency-0.07959144459757360.6291499267767720.999834320637052
IL7 vs. CD3-0.05282434753541240.869178029325290.916546833358059
SAHA vs. CD3-0.1611314220889710.6488039187386460.7384799890779
SAHA vs. IL7-0.08073678143894450.7409505710541450.881955851869091
(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 -0.0636904 0.716104
(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
0.96 0.932 0.933 1.019 0.931
(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
DB03276 4-[(10s,14s,18s)-18-(2-Amino-2-Oxoethyl)-14-(1-Naphthylmethyl)-8,17,20-Trioxo-7,16,19-Triazaspiro[5.14]Icos-11-En-10-Yl]Benzylphosphonic Acid experimental unknown unknown
DB00061 Pegademase bovine approved unknown binder

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1AZE NMR - A=1-56.
1BM2 X-ray 2.1Å A=49-163.
1BMB X-ray 1.8Å A=49-168.
1CJ1 X-ray 3.0Å A/B/C/D/E/F/G/H/I/J/K/L=57-152.
1FHS NMR - A=53-163.
1FYR X-ray 2.4Å A/B/C/D=50-161.
1GCQ X-ray 1.6Å A/B=159-217.
1GFC NMR - A=159-215.
1GFD NMR - A=159-215.
1GHU NMR - A=60-158.
1GRI X-ray 3.1Å A/B=1-217.
1IO6 NMR - A=159-215.
1JYQ X-ray 2.0Å A/B=60-151.
1JYR X-ray 1.5Å A=60-151.
1JYU X-ray 2.7Å A=60-151.
1QG1 NMR - E=58-159.
1TZE X-ray 2.1Å E=55-152.
1X0N NMR - A=58-159.
1ZFP X-ray 1.8Å E=56-153.
2AOA X-ray 1.9Å A/B=55-153.
2AOB X-ray 1.8Å A/B/C/D=55-153.
2H46 X-ray 1.9Å E=53-162.
2H5K X-ray 3.2Å A/B=53-162.
2HUW X-ray 1.9Å A/B=53-162.
2VVK X-ray 1.6Å A=161-214.
2VWF X-ray 1.5Å A=159-214.
2W0Z X-ray 1.7Å A=159-214.
3C7I X-ray 1.7Å A=53-162.
3IMD X-ray 2.0Å A/B=53-163.
3IMJ X-ray 2.0Å A/B=53-163.
3IN7 X-ray 2.0Å A/C=53-163.
3IN8 X-ray 1.7Å A=53-163.
3KFJ X-ray 2.0Å A=53-163.
3MXC X-ray 2.0Å A=55-152.
3MXY X-ray 2.3Å A=55-152.
3N7Y X-ray 2.0Å A/B/C=55-152.
3N84 X-ray 2.0Å A/B/C/D/E/F=53-163.
3N8M X-ray 2.0Å A=53-163.
3OV1 X-ray 1.6Å A=53-163.
3OVE X-ray 1.8Å A=53-163.
3S8L X-ray 1.7Å A=53-163.
3S8N X-ray 1.7Å A=53-163.
3S8O X-ray 1.8Å A=53-163.
3WA4 X-ray 1.3Å A=60-152.
4P9V X-ray 1.6Å A=53-163.
4P9Z X-ray 1.8Å A=53-163.
5CDW X-ray 2.6Å A/B/C/E/G/H/K/L/O/P/U/V/Y/Z/c/d=54-153.

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

HIV Partner Interaction Type PubMed
reverse transcriptase interacts with 22190034
Tat recruits 16436505
Pol interacts with 22190034
Tat upregulates 10906142
Tat binds 21745501
Nef upregulates 10906142

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01521 EGFR tyrosine kinase inhibitor resistance - Homo sapiens (human)
hsa01522 Endocrine resistance - Homo sapiens (human)
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04072 Phospholipase D signaling pathway - Homo sapiens (human)
hsa04150 mTOR signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04320 Dorso-ventral axis formation - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04540 Gap junction - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04630 Jak-STAT signaling pathway - Homo sapiens (human)
hsa04650 Natural killer cell mediated cytotoxicity - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04662 B cell receptor signaling pathway - Homo sapiens (human)
hsa04664 Fc epsilon RI signaling pathway - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04912 GnRH signaling pathway - Homo sapiens (human)
hsa04915 Estrogen signaling pathway - Homo sapiens (human)
hsa04917 Prolactin signaling pathway - Homo sapiens (human)
hsa05034 Alcoholism - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05211 Renal cell carcinoma - Homo sapiens (human)
hsa05213 Endometrial cancer - Homo sapiens (human)
hsa05214 Glioma - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05221 Acute myeloid leukemia - Homo sapiens (human)
hsa05223 Non-small cell lung cancer - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)
hsa05231 Choline metabolism in cancer - Homo sapiens (human)