Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008254
UniProt IDP08069
Primary gene name(s)IGF1R
Synonym gene name(s)unknown
Protein nameInsulin-like growth factor 1 receptor
Protein functionReceptor tyrosine kinase which mediates actions of insulin-like growth factor 1, IGF1. Binds IGF1 with high affinity and IGF2 and insulin, INS with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates, IRS1/2, Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K, PIK3R1, leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway, JAK/STAT. Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription, STAT proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.; FUNCTION: When present in a hybrid receptor with INSR, 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.
Subcellular locationCell membrane {ECO:0000269|PubMed:17524361};
Single-pass type I membrane protein {ECO:0000269|PubMed:17524361}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P08069
Gene Ontology
(Biological Process)
Complete annatation
immune response [GO:0006955];
inactivation of MAPKK activity [GO:0051389];
insulin-like growth factor receptor signaling pathway [GO:0048009];
insulin receptor signaling pathway [GO:0008286];
negative regulation of apoptotic process [GO:0043066];
peptidyl-tyrosine autophosphorylation [GO:0038083];
phosphatidylinositol 3-kinase signaling [GO:0014065];
phosphatidylinositol-mediated signaling [GO:0048015];
positive regulation of cell migration [GO:0030335];
positive regulation of cell proliferation [GO:0008284];
positive regulation of DNA replication [GO:0045740];
protein autophosphorylation [GO:0046777];
protein tetramerization [GO:0051262];
regulation of JNK cascade [GO:0046328];
signal transduction [GO:0007165]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
identical protein binding [GO:0042802];
insulin binding [GO:0043559];
insulin-like growth factor-activated receptor activity [GO:0005010];
insulin-like growth factor binding [GO:0005520];
insulin-like growth factor I binding [GO:0031994];
insulin receptor binding [GO:0005158];
insulin receptor substrate binding [GO:0043560];
phosphatidylinositol 3-kinase binding [GO:0043548];
protein tyrosine kinase activity [GO:0004713]
Gene Ontology
(Cellular Component)
Complete annatation
integral component of plasma membrane [GO:0005887];
intracellular membrane-bounded organelle [GO:0043231];
membrane [GO:0016020];
plasma membrane [GO:0005886];
receptor complex [GO:0043235]
Protein-protein interaction109701
Phylogenetic treeP08069
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. CD30.5149250610377610.1264940006023080.212472704455364
AZA vs. DISU0.2411663194108520.4834782276029430.931429104131977
AZA vs. IL7-0.1821032060220.5445400412640650.999311006273513
AZA vs. SAHA1.188246435713279.19360817297488e-060.00063280570593344
DISU vs. CD3-0.2889042631467290.4406654001808470.572094586368624
DISU vs. IL7-0.4313435214498250.2216792944116420.603966968081438
DISU vs. SAHA0.9491777989998610.003634107416722760.0516429059299863
DMSO vs. AZA-0.06841271152015870.7979425645583731
DMSO vs. CD3-0.5990285319787220.06719223056234990.123234837280473
DMSO vs. DISU-0.3120269491086110.3314751710747570.832624925724678
DMSO vs. IL7-0.106244154371790.6983425051393850.937788846060647
DMSO vs. SAHA1.250492088297942.69985600764855e-072.78695410214187e-05
HIV vs. Mock in Activation-0.1611158745499220.7963227408218180.999983755607037
HIV vs. Mock in Latency0.007839659087020910.9668011696217420.999834320637052
IL7 vs. CD3-0.6889970035081540.03777136664229170.0874812245542814
SAHA vs. CD30.6470466682637940.06916761130918620.129533478616806
SAHA vs. IL71.366090334646751.09632139166926e-064.91843710060193e-05
(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 -1.212 2.05E-11 4.64E-09
Infected vs. Bystander -1.448 5.04E-13 1.60E-10
(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 -0.928782 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
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
203628_at 4.32 No downregulated in CD8+ cells
203627_at 2.22 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB01277 Mecasermin approved, investigational yes agonist
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester experimental unknown unknown
DB00030 Insulin Human approved, investigational unknown unknown
DB00071 Insulin Pork approved unknown unknown
DB05023 ATL1101 investigational unknown unknown
DB05184 XL228 investigational unknown unknown
DB05759 IMC-A12 investigational unknown unknown
DB05897 rhIGFBP-3 investigational unknown unknown
DB05900 INSM-18 investigational unknown unknown
DB00047 Insulin Glargine approved unknown agonist
DB00046 Insulin Lispro approved unknown unknown
DB07156 (4Z)-6-bromo-4-({[4-(pyrrolidin-1-ylmethyl)phenyl]amino}methylidene)isoquinoline-1,3(2H,4H)-dione experimental unknown unknown
DB07474 3-[5-(1H-IMIDAZOL-1-YL)-7-METHYL-1H-BENZIMIDAZOL-2-YL]-4-[(PYRIDIN-2-YLMETHYL)AMINO]PYRIDIN-2(1H)-ONE experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1IGR X-ray 2.6Å A=31-492.
1JQH X-ray 2.1Å A/B/C=979-1286.
1K3A X-ray 2.1Å A=988-1286.
1M7N X-ray 2.7Å A/B=974-1294.
1P4O X-ray 1.5Å A/B=974-1294.
2OJ9 X-ray 2.0Å A=982-1286.
2ZM3 X-ray 2.5Å A/B/C/D=981-1286.
3D94 X-ray 2.3Å A=986-1286.
3F5P X-ray 2.9Å A/B/C/D/E/F/G/H/I/J/K/L/M/R/S/T=981-1286.
3I81 X-ray 2.0Å A=982-1286.
3LVP X-ray 3.0Å A/B/C/D=951-1286.
3LW0 X-ray 1.7Å A/B/C/D=983-1286.
3NW5 X-ray 2.1Å A=982-1286.
3NW6 X-ray 2.2Å A=982-1286.
3NW7 X-ray 2.1Å A=982-1286.
3O23 X-ray 2.1Å A=982-1286.
3QQU X-ray 2.9Å A/B/C/D=988-1286.
4D2R X-ray 2.1Å A=985-1286.
4XSS X-ray 3.0Å F=721-736.
5FXQ X-ray 2.3Å A=980-1286.
5FXR X-ray 2.4Å A=980-1286.
5FXS X-ray 1.9Å A=980-1286.
5HZN X-ray 2.2Å A/B/C/D/E/F/G/H=983-1286.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 upregulates 15103018

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)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04015 Rap1 signaling pathway - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04114 Oocyte meiosis - Homo sapiens (human)
hsa04144 Endocytosis - 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)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04520 Adherens junction - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04730 Long-term depression - Homo sapiens (human)
hsa04913 Ovarian steroidogenesis - Homo sapiens (human)
hsa04914 Progesterone-mediated oocyte maturation - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05214 Glioma - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05218 Melanoma - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)