Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001441
UniProt IDP06213
Primary gene name(s)INSR
Synonym gene name(s)unknown
Protein nameInsulin receptor
Protein functionReceptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates, IRS1, 2, 3, 4, SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains, SH2 domain that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5-triphosphate, PIP3, a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead, FOX class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors, IGFI and IGFII. Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. {ECO:0000269|PubMed:12138094, ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16831875, ECO:0000269|PubMed:8257688, ECO:0000269|PubMed:8276809, ECO:0000269|PubMed:8452530, ECO:0000269|PubMed:9428692}.
Subcellular locationCell membrane;
Single-pass type I membrane protein.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P06213
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPK activity [GO:0000187];
activation of protein kinase activity [GO:0032147];
activation of protein kinase B activity [GO:0032148];
adrenal gland development [GO:0030325];
carbohydrate metabolic process [GO:0005975];
cellular response to growth factor stimulus [GO:0071363];
cellular response to insulin stimulus [GO:0032869];
epidermis development [GO:0008544];
exocrine pancreas development [GO:0031017];
glucose homeostasis [GO:0042593];
G-protein coupled receptor signaling pathway [GO:0007186];
heart morphogenesis [GO:0003007];
insulin receptor signaling pathway [GO:0008286];
male gonad development [GO:0008584];
male sex determination [GO:0030238];
peptidyl-tyrosine autophosphorylation [GO:0038083];
peptidyl-tyrosine phosphorylation [GO:0018108];
positive regulation of cell migration [GO:0030335];
positive regulation of cell proliferation [GO:0008284];
positive regulation of developmental growth [GO:0048639];
positive regulation of DNA replication [GO:0045740];
positive regulation of glucose import [GO:0046326];
positive regulation of glycogen biosynthetic process [GO:0045725];
positive regulation of glycolytic process [GO:0045821];
positive regulation of MAPK cascade [GO:0043410];
positive regulation of meiotic cell cycle [GO:0051446];
positive regulation of mitotic nuclear division [GO:0045840];
positive regulation of nitric oxide biosynthetic process [GO:0045429];
positive regulation of protein kinase B signaling [GO:0051897];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of respiratory burst [GO:0060267];
positive regulation of transcription, DNA-templated [GO:0045893];
protein autophosphorylation [GO:0046777];
protein heterotetramerization [GO:0051290];
regulation of embryonic development [GO:0045995];
regulation of female gonad development [GO:2000194];
regulation of transcription, DNA-templated [GO:0006355];
transformation of host cell by virus [GO:0019087]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
GTP binding [GO:0005525];
insulin-activated receptor activity [GO:0005009];
insulin binding [GO:0043559];
insulin-like growth factor I binding [GO:0031994];
insulin-like growth factor II binding [GO:0031995];
insulin-like growth factor receptor binding [GO:0005159];
insulin receptor substrate binding [GO:0043560];
lipoic acid binding [GO:0031405];
phosphatidylinositol 3-kinase binding [GO:0043548];
protein tyrosine kinase activity [GO:0004713];
PTB domain binding [GO:0051425];
receptor signaling protein tyrosine kinase activity [GO:0004716]
Gene Ontology
(Cellular Component)
Complete annatation
caveola [GO:0005901];
cytosol [GO:0005829];
endosome membrane [GO:0010008];
extracellular exosome [GO:0070062];
insulin receptor complex [GO:0005899];
integral component of plasma membrane [GO:0005887];
intracellular membrane-bounded organelle [GO:0043231];
membrane [GO:0016020];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
receptor complex [GO:0043235];
synapse [GO:0045202]
Protein-protein interaction109854
Phylogenetic treeP06213
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. CD31.6172035137810.0006378987685226050.00245015551457
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3-1.018185435091170.02087700632403590.0533209070363465
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3-1.400860804572870.0006522722827810860.00235083300002322
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activation0.5467017969986080.509780103638120.999983755607037
HIV vs. Mock in Latency0.320054954884880.416802814895940.999834320637052
IL7 vs. CD3-1.640497156026910.0009515985187124040.00406445011973706
SAHA vs. CD3-0.8908598798551320.02701718037666730.0592992875438941
SAHA vs. IL7unknownunknownunknown
(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) 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 -0.244506 0.182787
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00030 Insulin Human approved, investigational yes agonist
DB00047 Insulin Glargine approved yes agonist
DB00071 Insulin Pork approved yes binder
DB03909 Adenosine-5&,39;-[Beta, Gamma-Methylene]Triphosphate experimental unknown unknown
DB05120 AT1391 investigational unknown unknown
DB05115 NN344 investigational unknown unknown
DB01307 Insulin Detemir approved yes agonist
DB00046 Insulin Lispro approved yes agonist
DB01306 Insulin Aspart approved yes agonist
DB01309 Insulin Glulisine approved yes agonist
DB01277 Mecasermin approved, investigational unknown unknown
DB08513 [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID experimental unknown unknown
DB09564 Insulin Degludec approved yes ligand

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1GAG X-ray 2.7Å A=1005-1310.
1I44 X-ray 2.4Å A=1005-1310.
1IR3 X-ray 1.9Å A=1005-1310.
1IRK X-ray 2.1Å A=1005-1310.
1P14 X-ray 1.9Å A=1005-1310.
1RQQ X-ray 2.6Å A/B=1005-1310.
2AUH X-ray 3.2Å A=1005-1310.
2B4S X-ray 2.3Å B/D=1005-1310.
2HR7 X-ray 2.3Å A/B=28-512.
2MFR NMR - A=940-988.
2Z8C X-ray 3.2Å A=1008-1310.
3BU3 X-ray 1.6Å A=1005-1310.
3BU5 X-ray 2.1Å A=1005-1310.
3BU6 X-ray 1.9Å A=1005-1310.
3EKK X-ray 2.1Å A=1005-1310.
3EKN X-ray 2.2Å A=1005-1310.
3ETA X-ray 2.6Å A/B=1017-1322.
3W11 X-ray 3.9Å E=28-337# F=731-744.
3W12 X-ray 4.3Å E=28-337# F=731-744.
3W13 X-ray 4.3Å E=28-337# F=724-744.
3W14 X-ray 4.4Å E/F=28-746.
4IBM X-ray 1.8Å A/B=1005-1310.
4OGA X-ray 3.5Å E=28-337# F=731-744.
4XLV X-ray 2.3Å A=983-1310.
4XSS X-ray 3.0Å E=28-337.
4XST X-ray 3.0Å E=28-337.
4ZXB X-ray 3.3Å E=28-956.
5E1S X-ray 2.2Å A=1005-1310.
5HHW X-ray 1.7Å A=1005-1310.
5J3H X-ray 3.2Å E=28-337.

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
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04015 Rap1 signaling pathway - Homo sapiens (human)
hsa04022 cGMP-PKG signaling pathway - Homo sapiens (human)
hsa04066 HIF-1 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)
hsa04152 AMPK signaling pathway - Homo sapiens (human)
hsa04211 Longevity regulating pathway - Homo sapiens (human)
hsa04213 Longevity regulating pathway - multiple species - Homo sapiens (human)
hsa04520 Adherens junction - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04913 Ovarian steroidogenesis - 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)
hsa04960 Aldosterone-regulated sodium reabsorption - Homo sapiens (human)
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