Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002185
UniProt IDP27986
Primary gene name(s)PIK3R1
Synonym gene name(s)GRB1
Protein namePhosphatidylinositol 3-kinase regulatory subunit alpha
Protein functionBinds to activated, phosphorylated protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling, PubMed:17626883, PubMed:19805105, PubMed:7518429. Modulates the cellular response to ER stress by promoting nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement, PubMed:20348923. {ECO:0000269|PubMed:17626883, ECO:0000269|PubMed:19805105, ECO:0000269|PubMed:20348923, ECO:0000269|PubMed:7518429}.
Subcellular locationunknown
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P27986
Gene Ontology
(Biological Process)
Complete annatation
B cell differentiation [GO:0030183];
cellular glucose homeostasis [GO:0001678];
cellular response to insulin stimulus [GO:0032869];
cellular response to UV [GO:0034644];
epidermal growth factor receptor signaling pathway [GO:0007173];
ERBB2 signaling pathway [GO:0038128];
extrinsic apoptotic signaling pathway via death domain receptors [GO:0008625];
Fc-epsilon receptor signaling pathway [GO:0038095];
Fc-gamma receptor signaling pathway involved in phagocytosis [GO:0038096];
growth hormone receptor signaling pathway [GO:0060396];
insulin-like growth factor receptor signaling pathway [GO:0048009];
insulin receptor signaling pathway [GO:0008286];
intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630];
leukocyte migration [GO:0050900];
negative regulation of apoptotic process [GO:0043066];
negative regulation of cell-matrix adhesion [GO:0001953];
negative regulation of osteoclast differentiation [GO:0045671];
NFAT protein import into nucleus [GO:0051531];
phosphatidylinositol 3-kinase signaling [GO:0014065];
phosphatidylinositol biosynthetic process [GO:0006661];
phosphatidylinositol-mediated signaling [GO:0048015];
phosphatidylinositol phosphorylation [GO:0046854];
platelet activation [GO:0030168];
positive regulation of cell migration [GO:0030335];
positive regulation of endoplasmic reticulum unfolded protein response [GO:1900103];
positive regulation of establishment of protein localization to plasma membrane [GO:0090004];
positive regulation of glucose import [GO:0046326];
positive regulation of glucose import in response to insulin stimulus [GO:2001275];
positive regulation of RNA splicing [GO:0033120];
positive regulation of transcription factor import into nucleus [GO:0042993];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of tumor necrosis factor production [GO:0032760];
protein phosphorylation [GO:0006468];
protein stabilization [GO:0050821];
regulation of phosphatidylinositol 3-kinase activity [GO:0043551];
regulation of phosphatidylinositol 3-kinase signaling [GO:0014066];
regulation of stress fiber assembly [GO:0051492];
response to endoplasmic reticulum stress [GO:0034976];
T cell costimulation [GO:0031295];
T cell receptor signaling pathway [GO:0050852];
vascular endothelial growth factor receptor signaling pathway [GO:0048010];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
1-phosphatidylinositol-3-kinase activity [GO:0016303];
1-phosphatidylinositol-3-kinase regulator activity [GO:0046935];
ErbB-3 class receptor binding [GO:0043125];
insulin binding [GO:0043559];
insulin-like growth factor receptor binding [GO:0005159];
insulin receptor binding [GO:0005158];
insulin receptor substrate binding [GO:0043560];
neurotrophin TRKA receptor binding [GO:0005168];
phosphatidylinositol 3-kinase binding [GO:0043548];
phosphatidylinositol 3-kinase regulator activity [GO:0035014];
phosphatidylinositol-4,5-bisphosphate 3-kinase activity [GO:0046934];
protein phosphatase binding [GO:0019903];
transcription factor binding [GO:0008134];
transmembrane receptor protein tyrosine kinase adaptor activity [GO:0005068]
Gene Ontology
(Cellular Component)
Complete annatation
cell-cell junction [GO:0005911];
cis-Golgi network [GO:0005801];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
membrane [GO:0016020];
nucleus [GO:0005634];
perinuclear endoplasmic reticulum membrane [GO:1990578];
phosphatidylinositol 3-kinase complex [GO:0005942];
phosphatidylinositol 3-kinase complex, class IA [GO:0005943];
plasma membrane [GO:0005886]
Protein-protein interaction111313
Phylogenetic treeP27986
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. CD3-1.730983838805572.71366475068646e-072.37931094370834e-06
AZA vs. DISU-0.2150019865241820.3946203516684760.902586488791209
AZA vs. IL7-0.09140540792130780.6334696284464770.999311006273513
AZA vs. SAHA-0.2908892660952260.2329040868187480.603748272520346
DISU vs. CD31.503878903241294.76499326849122e-050.000296685289257483
DISU vs. IL70.1146924186974160.6481978781786710.898171239645597
DISU vs. SAHA-0.07569068549284030.7946926075186110.945811599772012
DMSO vs. AZA-0.1391409201158050.4044306517457571
DMSO vs. CD31.581195516774481.35264773415411e-069.46916269285859e-06
DMSO vs. DISU0.07415070232607010.7607421222032180.969857060964769
DMSO vs. IL70.05486308518139360.759555411119040.951841190064606
DMSO vs. SAHA-0.1597680675073080.4974769360319720.812534525641619
HIV vs. Mock in Activation0.318252931212130.6104507607236980.999983755607037
HIV vs. Mock in Latency0.07977796367330840.6276821323816670.999834320637052
IL7 vs. CD31.64817870356815.51214912603015e-075.70244500869269e-06
SAHA vs. CD31.414273330010248.36429123260984e-050.000410051622886891
SAHA vs. IL7-0.2040642333857750.4012619252310270.64827619624001
(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 -0.617259 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
1.044 1.13 1.133 1.189 1.177
(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
DB01064 Isoprenaline approved unknown agonist
DB05210 SF1126 investigational unknown unknown
DB08059 (1S,6BR,9AS,11R,11BR)-9A,11B-DIMETHYL-1-[(METHYLOXY)METHYL]-3,6,9-TRIOXO-1,6,6B,7,8,9,9A,10,11,11B-DECAHYDRO-3H-FURO[4,3,2-DE]INDENO[4,5-H][2]BENZOPYRAN-11-YL ACETATE experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1A0N NMR - A=91-104.
1AZG NMR - A=91-104.
1H9O X-ray 1.7Å A=617-724.
1PBW X-ray 2.0Å A/B=105-319.
1PHT X-ray 2.0Å A=1-85.
1PIC NMR - A=617-724.
1PKS NMR - A=1-79.
1PKT NMR - A=1-79.
2IUG X-ray 1.8Å A=321-440.
2IUH X-ray 2.0Å A=321-440.
2IUI X-ray 2.4Å A/B=321-440.
2RD0 X-ray 3.0Å B=322-600.
2V1Y X-ray 2.4Å B=431-600.
3HHM X-ray 2.8Å B=322-694.
3HIZ X-ray 3.3Å B=322-694.
3I5R X-ray 1.7Å A=1-83.
3I5S X-ray 3.0Å A/B/C/D=1-83.
4A55 X-ray 3.5Å B=322-600.
4JPS X-ray 2.2Å B=307-593.
4L1B X-ray 2.5Å B=318-615.
4L23 X-ray 2.5Å B=318-615.
4L2Y X-ray 2.8Å B=318-615.
4OVU X-ray 2.9Å B=322-600.
4OVV X-ray 3.5Å B=322-600.
4WAF X-ray 2.3Å B=306-617.
4YKN X-ray 2.9Å A=318-615.
4ZOP X-ray 2.6Å B=307-590.
5AUL X-ray 1.1Å A=614-720.
5FI4 X-ray 2.5Å B=306-617.
5ITD X-ray 3.0Å B=307-617.

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

HIV Partner Interaction Type PubMed
Nef interacts with 11289809
Tat activates 17157319
Nef associates with 24229420
Envelope surface glycoprotein gp120 modulated by 16524887
Envelope surface glycoprotein gp160; precursor inhibits 9808187
Envelope surface glycoprotein gp160; precursor activates 9341793
Envelope surface glycoprotein gp120 mediated by 16081599
Tat interacts with 11154208
Envelope surface glycoprotein gp120 induces phosphorylation of 9123823
Nef complexes with 18854243
Nef binds 11689886
Tat inhibited by 12077252
Envelope surface glycoprotein gp120 inhibited by 20818790
Envelope surface glycoprotein gp120 relocalizes 18453587
Tat induces phosphorylation of 23301033
Nef downregulates 8636073
Tat regulated by 24073214
Envelope surface glycoprotein gp120 activates 12551992
Envelope surface glycoprotein gp120 regulated by 15689238
Nef activates 25104021
Nef upregulates 10985305

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)
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04015 Rap1 signaling pathway - Homo sapiens (human)
hsa04022 cGMP-PKG signaling pathway - Homo sapiens (human)
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04070 Phosphatidylinositol signaling system - Homo sapiens (human)
hsa04071 Sphingolipid 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)
hsa04152 AMPK signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04211 Longevity regulating pathway - Homo sapiens (human)
hsa04213 Longevity regulating pathway - multiple species - Homo sapiens (human)
hsa04261 Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
hsa04360 Axon guidance - Homo sapiens (human)
hsa04370 VEGF signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04611 Platelet activation - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - 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)
hsa04666 Fc gamma R-mediated phagocytosis - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04670 Leukocyte transendothelial migration - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04725 Cholinergic synapse - Homo sapiens (human)
hsa04750 Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
hsa04810 Regulation of actin cytoskeleton - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04914 Progesterone-mediated oocyte maturation - Homo sapiens (human)
hsa04915 Estrogen signaling pathway - Homo sapiens (human)
hsa04917 Prolactin signaling pathway - Homo sapiens (human)
hsa04919 Thyroid hormone signaling pathway - Homo sapiens (human)
hsa04921 Oxytocin signaling pathway - Homo sapiens (human)
hsa04923 Regulation of lipolysis in adipocytes - Homo sapiens (human)
hsa04930 Type II diabetes mellitus - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa04960 Aldosterone-regulated sodium reabsorption - Homo sapiens (human)
hsa04973 Carbohydrate digestion and absorption - Homo sapiens (human)
hsa05100 Bacterial invasion of epithelial cells - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05146 Amoebiasis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05210 Colorectal cancer - Homo sapiens (human)
hsa05211 Renal cell carcinoma - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05213 Endometrial cancer - Homo sapiens (human)
hsa05214 Glioma - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05218 Melanoma - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05221 Acute myeloid leukemia - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)
hsa05223 Non-small cell lung cancer - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)
hsa05230 Central carbon metabolism in cancer - Homo sapiens (human)
hsa05231 Choline metabolism in cancer - Homo sapiens (human)