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Aliases for INSR Gene

Aliases for INSR Gene

  • Insulin Receptor 2 3 5
  • EC 2.7.10.1 4 61
  • IR 3 4
  • CD220 Antigen 4
  • EC 2.7.10 61
  • CD220 3
  • HHF5 3

External Ids for INSR Gene

Previous GeneCards Identifiers for INSR Gene

  • GC19M007225
  • GC19M007056
  • GC19M007067
  • GC19M006847

Summaries for INSR Gene

Entrez Gene Summary for INSR Gene

  • This gene encodes a member of the receptor tyrosine kinase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form a heterotetrameric receptor. Binding of insulin or other ligands to this receptor activates the insulin signaling pathway, which regulates glucose uptake and release, as well as the synthesis and storage of carbohydrates, lipids and protein. Mutations in this gene underlie the inherited severe insulin resistance syndromes including type A insulin resistance syndrome, Donohue syndrome and Rabson-Mendenhall syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

GeneCards Summary for INSR Gene

INSR (Insulin Receptor) is a Protein Coding gene. Diseases associated with INSR include Rabson-Mendenhall Syndrome and Leprechaunism. Among its related pathways are RET signaling and Activation of cAMP-Dependent PKA. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is IGF1R.

UniProtKB/Swiss-Prot for INSR Gene

  • Receptor 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.

Tocris Summary for INSR Gene

  • Insulin receptors (IRs) and insulin-like growth factor receptors (IGFRs) are formed from two subunits, each of which is comprised of an extracellular alpha-subunit and a transmembrane beta-subunit with intracellular tyrosine kinase activity. IR homodimers are activated by insulin.

Gene Wiki entry for INSR Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for INSR Gene

Genomics for INSR Gene

Regulatory Elements for INSR Gene

Enhancers for INSR Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH19F007196 1.7 FANTOM5 Ensembl ENCODE 6.9 +95.3 95342 5.0 HDGF PKNOX1 ARNT MLX CREB3L1 WRNIP1 ARID4B SIN3A DMAP1 ZNF2 ELAVL1 ZNF557 XAB2 GTF2F1 ARHGEF18 INSR RETN CAMSAP3 GC19P007214 GC19P007151
GH19F007205 1.3 Ensembl ENCODE 6.9 +82.8 82843 10.5 HDGF PKNOX1 MLX ARID4B DMAP1 ZNF48 YY1 ZNF207 KLF7 PAF1 ARHGEF18 INSR SH2D3A ADGRE1 TRIP10 GC19P007214 GC19P007151
GH19F007272 1 Ensembl ENCODE 6.4 +21.1 21077 1.5 TBL1XR1 EBF1 EGR1 EED ZNF548 EGR2 CHD2 MTA2 CBFB BHLHE40 ELAVL1 XAB2 ZNF557 INSR GC19P007214
GH19F007177 1.2 Ensembl ENCODE 4.9 +113.0 112960 7.1 HDGF PKNOX1 SIN3A FEZF1 ZNF121 ZNF302 CBX5 ZNF143 ZNF207 ZNF202 ELAVL1 XAB2 ZNF557 GTF2F1 ARHGEF18 INSR GC19P007151 GC19P007214
GH19F007223 1 Ensembl ENCODE 5.8 +69.6 69648 1.4 SOX13 ELF3 SAP130 ZMYM3 RAD21 ZNF644 ZSCAN9 ZNF48 YY1 ADNP INSR GC19P007214
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around INSR on UCSC Golden Path with GeneCards custom track

Promoters for INSR Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000342805 134 3001 HDGF PKNOX1 MLX WRNIP1 ARID4B SIN3A YBX1 ZNF2 YY1 ZNF207

Genomic Location for INSR Gene

Chromosome:
19
Start:
7,112,255 bp from pter
End:
7,294,034 bp from pter
Size:
181,780 bases
Orientation:
Minus strand

Genomic View for INSR Gene

Genes around INSR on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
INSR Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for INSR Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for INSR Gene

Proteins for INSR Gene

  • Protein details for INSR Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P06213-INSR_HUMAN
    Recommended name:
    Insulin receptor
    Protein Accession:
    P06213
    Secondary Accessions:
    • Q17RW0
    • Q59H98
    • Q9UCB7
    • Q9UCB8
    • Q9UCB9

    Protein attributes for INSR Gene

    Size:
    1382 amino acids
    Molecular mass:
    156333 Da
    Quaternary structure:
    • Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains carry the insulin-binding regions, while the beta chains carry the kinase domain. Forms a hybrid receptor with IGF1R, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with SORBS1 but dissociates from it following insulin stimulation. Binds SH2B2. Activated form of INSR interacts (via Tyr-999) with the PTB/PID domains of IRS1 and SHC1. The sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition. Interacts (via tyrosines in the C-terminus) with IRS2 (via PTB domain and 591-786 AA); the 591-786 would be the primary anchor of IRS2 to INSR while the PTB domain would have a stabilizing action on the interaction with INSR. Interacts with the SH2 domains of the 85 kDa regulatory subunit of PI3K (PIK3R1) in vitro, when autophosphorylated on tyrosine residues. Interacts with SOCS7. Interacts (via the phosphorylated Tyr-999), with SOCS3. Interacts (via the phosphorylated Tyr-1185, Tyr-1189, Tyr-1190) with SOCS1. Interacts with CAV2 (tyrosine-phosphorylated form); the interaction is increased with Tyr-27phosphorylation of CAV2 (By similarity). Interacts with ARRB2 (By similarity). Interacts with GRB10; this interaction blocks the association between IRS1/IRS2 and INSR, significantly reduces insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2 and thus decreases insulin signaling. Interacts with GRB7. Interacts with PDPK1. Interacts (via Tyr-1190) with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop from dephosphorylation, but promotes dephosphorylation of Tyr-999, this results in decreased interaction with, and phosphorylation of, IRS1. Interacts (via subunit alpha) with ENPP1 (via 485-599 AA); this interaction blocks autophosphorylation. Interacts with PTPRE; this interaction is dependent of Tyr-1185, Tyr-1189 and Tyr-1190 of the INSR. Interacts with STAT5B (via SH2 domain). Interacts with PTPRF. Interacts with ATIC; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling netwok regulating INSR autophosphorylation and endocytosis (By similarity).

    Three dimensional structures from OCA and Proteopedia for INSR Gene

    Alternative splice isoforms for INSR Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for INSR Gene

Selected DME Specific Peptides for INSR Gene

P06213:
  • DGQDACG
  • LMRMCWQ
  • PESLKDG
  • RDLAARN
  • YALVIFEM
  • KCIPECPSGYT
  • YVPDEWEV
  • FPNLTVI
  • GLLPVRWM
  • GVVLWEI
  • RERIEFLNEASVMK
  • FGMVYEG
  • HCQKVCP
  • KTIDSVTSAQ
  • LFFNYALV
  • KFVHRDLAARNCMV
  • HVVRLLGV
  • NITRGSVRIEKN
  • EGHLQILLMF
  • PNGNITHY
  • TDYLLLFRVYGLESL
  • LKPWTQYA
  • HFTGYRIE
  • SQIILKWKPPS
  • DGMAYLNA
  • EIADGMAYL
  • RTYGAKS
  • FVHRDLA
  • QPYQGLSNE
  • GPCPKVC
  • KGLKLPSRTW
  • PNGLIVLYEV

Post-translational modifications for INSR Gene

  • After being transported from the endoplasmic reticulum to the Golgi apparatus, the single glycosylated precursor is further glycosylated and then cleaved, followed by its transport to the plasma membrane.
  • Autophosphorylated on tyrosine residues in response to insulin. Phosphorylation of Tyr-999 is required for binding to IRS1, SHC1 and STAT5B. Dephosphorylated by PTPRE at Tyr-999, Tyr-1185, Tyr-1189 and Tyr-1190. Dephosphorylated by PTPRF and PTPN1. Dephosphorylated by PTPN2; down-regulates insulin-induced signaling.
  • Ubiquitination at Lys 1057
  • Glycosylation at Asn 43, Asn 52, Asn 105, Asn 138, Asn 242, Asn 282, Asn 322, Asn 364, Asn 424, Asn 445, Asn 541, Asn 633, Asn 651, Asn 698, Asn 769, Asn 782, Asn 920, and Asn 933
  • Modification sites at PhosphoSitePlus

Other Protein References for INSR Gene

Antibody Products

  • R&D Systems Antibodies for INSR (Insulin R/CD220)
  • Cell Signaling Technology (CST) Antibodies for INSR (INSR)

Protein Products

Domains & Families for INSR Gene

Suggested Antigen Peptide Sequences for INSR Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P06213

UniProtKB/Swiss-Prot:

INSR_HUMAN :
  • The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2.
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Domain:
  • The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2.
  • Contains 3 fibronectin type-III domains.
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
genes like me logo Genes that share domains with INSR: view

Function for INSR Gene

Molecular function for INSR Gene

GENATLAS Biochemistry:
insulin receptor precursor of two subunits alpha and beta
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated in response to insulin. Autophosphorylation activates the kinase activity. PTPN1, PTPRE and PTPRF dephosphorylate important tyrosine residues, thereby reducing INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the catalytic activity of the INSR, they block access of substrates to the activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR activity, they bind to the activated INRS and interfere with the phosphorylation of INSR substrates.
UniProtKB/Swiss-Prot Function:
Receptor 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.

Enzyme Numbers (IUBMB) for INSR Gene

Gene Ontology (GO) - Molecular Function for INSR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA --
GO:0004713 protein tyrosine kinase activity IMP 7537849
GO:0004714 transmembrane receptor protein tyrosine kinase activity IEA --
GO:0004716 signal transducer, downstream of receptor, with protein tyrosine kinase activity IDA 6849137
GO:0005009 insulin-activated receptor activity IDA 6849137
genes like me logo Genes that share ontologies with INSR: view
genes like me logo Genes that share phenotypes with INSR: view

Human Phenotype Ontology for INSR Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for INSR Gene

MGI Knock Outs for INSR:

Animal Model Products

miRNA for INSR Gene

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for INSR

Flow Cytometry Products

No data available for Transcription Factor Targets and HOMER Transcription for INSR Gene

Localization for INSR Gene

Subcellular locations from UniProtKB/Swiss-Prot for INSR Gene

Cell membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for INSR gene
Compartment Confidence
plasma membrane 5
extracellular 5
endosome 4
mitochondrion 1
nucleus 1
cytosol 1

Gene Ontology (GO) - Cellular Components for INSR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IEA,TAS --
GO:0005887 integral component of plasma membrane IDA 9092559
GO:0005899 insulin receptor complex IMP 15069075
GO:0005901 caveola IEA,IDA 15182363
GO:0010008 endosome membrane TAS --
genes like me logo Genes that share ontologies with INSR: view

Pathways & Interactions for INSR Gene

genes like me logo Genes that share pathways with INSR: view

Pathways by source for INSR Gene

Interacting Proteins for INSR Gene

SIGNOR curated interactions for INSR Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for INSR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000187 activation of MAPK activity IMP 17001305
GO:0001934 positive regulation of protein phosphorylation IDA 7556070
GO:0003007 heart morphogenesis IMP 7693131
GO:0005975 carbohydrate metabolic process IEA --
GO:0006355 regulation of transcription, DNA-templated IMP 12881524
genes like me logo Genes that share ontologies with INSR: view

Drugs & Compounds for INSR Gene

(92) Drugs for INSR Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Insulin Aspart Approved Pharma Target, agonist 442
Insulin Detemir Approved Pharma Target, agonist 196
Insulin Glargine Approved Pharma Target, agonist 522
Insulin-glulisine Approved Pharma Target, agonist 104
Insulin Degludec Approved Pharma Target, ligand 0

(55) Additional Compounds for INSR Gene - From: Novoseek, Tocris, and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
6bK
1774353-12-6
BMS 536924
468740-43-4
Insulin (human) recombinant
11061-68-0
Picropodophyllotoxin
477-47-4

(5) Tocris Compounds for INSR Gene

Compound Action Cas Number
6bK Insulin degrading enzyme (IDE) inhibitor 1774353-12-6
BMS 536924 Dual IR/IGF1R inhibitor 468740-43-4
Insulin (human) recombinant Endogenous peptide agonist 11061-68-0
Mitoglitazone Insulin sensitizer; exhibits low binding affinity at PPARgamma 146062-49-9
Picropodophyllotoxin Selective IGF1R inhibitor 477-47-4

(7) ApexBio Compounds for INSR Gene

Compound Action Cas Number
BMS-536924 IR/IGF-1R inhibitor 468740-43-4
BMS-754807 IGF-1R/InsR inhibitor,potent and selective 1001350-96-4
Demethylasterriquinone B1 78860-34-1
GSK1838705A IGF-IR/IR/ALK inhibitor, ATP-competitive 1116235-97-2
GSK1904529A Selective IGF-1R/IR inhibitor 1089283-49-7
HNGF6A 1093111-54-6
Linsitinib IGF1R/IR inhibitor,potent and novel 867160-71-2
genes like me logo Genes that share compounds with INSR: view

Drug Products

Transcripts for INSR Gene

Unigene Clusters for INSR Gene

Insulin receptor:
Representative Sequences:

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for INSR

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for INSR Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22
SP1: -
SP2: - -
SP3:

Relevant External Links for INSR Gene

GeneLoc Exon Structure for
INSR
ECgene alternative splicing isoforms for
INSR

Expression for INSR Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for INSR Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for INSR Gene

This gene is overexpressed in Pancreas (x4.2).

Protein differential expression in normal tissues from HIPED for INSR Gene

This gene is overexpressed in Plasma (10.2), Pancreas (9.9), and Placenta (8.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for INSR Gene



Protein tissue co-expression partners for INSR Gene

NURSA nuclear receptor signaling pathways regulating expression of INSR Gene:

INSR

SOURCE GeneReport for Unigene cluster for INSR Gene:

Hs.465744

mRNA Expression by UniProt/SwissProt for INSR Gene:

P06213-INSR_HUMAN
Tissue specificity: Isoform Long and isoform Short are predominantly expressed in tissue targets of insulin metabolic effects: liver, adipose tissue and skeletal muscle but are also expressed in the peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta vascular endothelium, fibroblasts, monocytes, granulocytes, erythrocytes and skin. Isoform Short is preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas.
genes like me logo Genes that share expression patterns with INSR: view

Primer Products

Orthologs for INSR Gene

This gene was present in the common ancestor of animals.

Orthologs for INSR Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia INSR 34 35
  • 99.21 (n)
cow
(Bos Taurus)
Mammalia IR-A 35
  • 95 (a)
OneToOne
INSR 34
  • 89.7 (n)
dog
(Canis familiaris)
Mammalia INSR 34 35
  • 88.91 (n)
mouse
(Mus musculus)
Mammalia Insr 34 16 35
  • 87.34 (n)
rat
(Rattus norvegicus)
Mammalia Insr 34
  • 87.23 (n)
oppossum
(Monodelphis domestica)
Mammalia INSR 35
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia INSR 35
  • 70 (a)
OneToOne
chicken
(Gallus gallus)
Aves CTK-1 35
  • 82 (a)
OneToOne
INSR 34
  • 77 (n)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100492718 34
  • 67.83 (n)
African clawed frog
(Xenopus laevis)
Amphibia LOC398006 34
zebrafish
(Danio rerio)
Actinopterygii insra 34 35
  • 69.41 (n)
insrb 35
  • 67 (a)
OneToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8035 34
fruit fly
(Drosophila melanogaster)
Insecta InR 36
  • 36 (a)
CG3837 36 35
  • 29 (a)
CG10702 36
  • 26 (a)
worm
(Caenorhabditis elegans)
Secernentea W02A2.4 36
  • 37 (a)
K09B11.5 36
  • 36 (a)
T21G5.1 36
  • 33 (a)
T25B9.5 36
  • 30 (a)
Y69E1A.3 36
  • 30 (a)
daf-2 35
  • 24 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 40 (a)
OneToMany
Species where no ortholog for INSR was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for INSR Gene

ENSEMBL:
Gene Tree for INSR (if available)
TreeFam:
Gene Tree for INSR (if available)

Paralogs for INSR Gene

Paralogs for INSR Gene

(23) SIMAP similar genes for INSR Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with INSR: view

Variants for INSR Gene

Sequence variations from dbSNP and Humsavar for INSR Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs111993466 Rabson-Mendenhall syndrome (RMS) [MIM:262190] 7,122,671(+) GTCCC(A/G)ATGCA reference, missense
rs121913135 Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549], Pathogenic 7,125,437(-) CTTCG(G/T)CATGG reference, missense
rs121913138 Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549], Pathogenic 7,143,072(-) CGCAG(G/T)TCCCT reference, missense
rs121913140 Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549], Pathogenic 7,119,563(-) CCTTT(C/G)GGAAA reference, missense
rs121913141 Leprechaunism (LEPRCH) [MIM:246200], Pathogenic 7,184,511(-) CTACC(C/T)GGACG reference, missense

Structural Variations from Database of Genomic Variants (DGV) for INSR Gene

Variant ID Type Subtype PubMed ID
dgv1017e212 CNV loss 25503493
dgv1018e212 CNV loss 25503493
dgv1019e212 CNV loss 25503493
dgv136e55 CNV gain 17911159
dgv3421n100 CNV gain 25217958
dgv3423n100 CNV gain 25217958
dgv3424n100 CNV gain 25217958
dgv393n27 CNV gain 19166990
dgv395n27 CNV gain 19166990
dgv6237n54 CNV gain 21841781
dgv6245n54 CNV gain 21841781
dgv6246n54 CNV gain 21841781
esv1005113 CNV deletion 20482838
esv1122975 CNV insertion 17803354
esv1602115 CNV deletion 17803354
esv1934161 CNV deletion 18987734
esv2568778 CNV insertion 19546169
esv2600509 CNV insertion 19546169
esv26586 CNV loss 19812545
esv2659640 CNV deletion 23128226
esv2667178 CNV deletion 23128226
esv2671138 CNV deletion 23128226
esv2673294 CNV deletion 23128226
esv2675376 CNV deletion 23128226
esv2718083 CNV deletion 23290073
esv2718085 CNV deletion 23290073
esv2718086 CNV deletion 23290073
esv2718087 CNV deletion 23290073
esv2718088 CNV deletion 23290073
esv2751809 CNV gain 17911159
nsv578502 CNV gain 21841781
nsv578500 CNV gain 21841781
nsv524177 CNV loss 19592680
nsv521868 CNV loss 19592680
nsv521213 CNV gain 19592680
nsv513513 CNV insertion 21212237
nsv480227 CNV novel sequence insertion 20440878
nsv479065 CNV novel sequence insertion 20440878
nsv478625 CNV novel sequence insertion 20440878
nsv476950 CNV novel sequence insertion 20440878
nsv475210 CNV novel sequence insertion 20440878
nsv474542 CNV novel sequence insertion 20440878
nsv473511 CNV novel sequence insertion 20440878
nsv473021 CNV novel sequence insertion 20440878
nsv458347 CNV gain 19166990
nsv1141947 OTHER inversion 24896259
nsv1138663 CNV deletion 24896259
nsv1133253 CNV tandem duplication 24896259
nsv1131392 CNV deletion 24896259
nsv1125376 OTHER inversion 24896259
nsv1113966 CNV deletion 24896259
nsv1060887 CNV gain 25217958
nsv1060476 CNV gain 25217958
nsv1058745 CNV loss 25217958
nsv1057262 CNV gain 25217958
nsv1056752 CNV gain 25217958
esv9300 CNV loss 19470904
esv3893162 CNV loss 25118596
esv3643581 CNV loss 21293372
esv3643580 CNV loss 21293372
esv3643579 CNV loss 21293372
esv3583229 CNV loss 25503493
esv3555964 CNV deletion 23714750
esv3383975 CNV duplication 20981092
esv3302902 CNV tandem duplication 20981092
esv3302632 CNV tandem duplication 20981092

Variation tolerance for INSR Gene

Residual Variation Intolerance Score: 3.75% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.60; 44.99% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for INSR Gene

Human Gene Mutation Database (HGMD)
INSR
SNPedia medical, phenotypic, and genealogical associations of SNPs for
INSR

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for INSR Gene

Disorders for INSR Gene

MalaCards: The human disease database

(27) MalaCards diseases for INSR Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
rabson-mendenhall syndrome
  • pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities
leprechaunism
  • donohue syndrome
diabetes mellitus, insulin-resistant, with acanthosis nigricans
  • insulin receptor, defect in, with insulin-resistant diabetes mellitus and acanthosis nigricans
hyperinsulinemic hypoglycemia, familial, 5
  • hyperinsulinism due to insr deficiency
insr-related hyperinsulinism
  • hyperinsulinemic hypoglycemia, familial, 5
- elite association - COSMIC cancer census association via MalaCards
Search INSR in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

INSR_HUMAN
  • Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the bodys own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269 PubMed:1470163, ECO:0000269 PubMed:1607076, ECO:0000269 PubMed:7657032}. Note=The gene represented in this entry may be involved in disease pathogenesis.
  • Familial hyperinsulinemic hypoglycemia 5 (HHF5) [MIM:609968]: Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. {ECO:0000269 PubMed:15161766}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:610549]: Characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor. {ECO:0000269 PubMed:10733238, ECO:0000269 PubMed:11260230, ECO:0000269 PubMed:12107746, ECO:0000269 PubMed:12970295, ECO:0000269 PubMed:1563582, ECO:0000269 PubMed:1963473, ECO:0000269 PubMed:2002058, ECO:0000269 PubMed:2168397, ECO:0000269 PubMed:2365819, ECO:0000269 PubMed:2544998, ECO:0000269 PubMed:3283938, ECO:0000269 PubMed:8243830, ECO:0000269 PubMed:8288049, ECO:0000269 PubMed:8314008, ECO:0000269 PubMed:8388389, ECO:0000269 PubMed:9175790}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Leprechaunism (LEPRCH) [MIM:246200]: Represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive. {ECO:0000269 PubMed:12538626, ECO:0000269 PubMed:12970295, ECO:0000269 PubMed:1607067, ECO:0000269 PubMed:1730625, ECO:0000269 PubMed:2365819, ECO:0000269 PubMed:2479553, ECO:0000269 PubMed:2834824, ECO:0000269 PubMed:7538143, ECO:0000269 PubMed:7815442, ECO:0000269 PubMed:8188715, ECO:0000269 PubMed:8326490, ECO:0000269 PubMed:8419945, ECO:0000269 PubMed:8636294, ECO:0000269 PubMed:9249867, ECO:0000269 PubMed:9703342}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Rabson-Mendenhall syndrome (RMS) [MIM:262190]: Severe insulin resistance syndrome characterized by insulin-resistant diabetes mellitus with pineal hyperplasia and somatic abnormalities. Typical features include coarse, senile-appearing facies, dental and skin abnormalities, abdominal distension, and phallic enlargement. Inheritance is autosomal recessive. {ECO:0000269 PubMed:10443650, ECO:0000269 PubMed:12023989, ECO:0000269 PubMed:17201797, ECO:0000269 PubMed:2365819, ECO:0000269 PubMed:8314008}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for INSR Gene

insulin resistance,type A (hyperinsulinemia,decreased insulin binding,acanthocytosis)

Relevant External Links for INSR

Genetic Association Database (GAD)
INSR
Human Genome Epidemiology (HuGE) Navigator
INSR
Tumor Gene Database (TGDB):
INSR
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
INSR
genes like me logo Genes that share disorders with INSR: view

Publications for INSR Gene

  1. Insulin resistance-related genes and advanced left-sided colorectal adenoma. (PMID: 17416760) Gunter M.J. … Peters U. (Cancer Epidemiol. Biomarkers Prev. 2007) 3 22 46 64
  2. Hybrid receptors formed by insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) have low insulin and high IGF-1 affinity irrespective of the IR splice variant. (PMID: 16831875) Slaaby R. … Brandt J. (J. Biol. Chem. 2006) 3 4 22 64
  3. Crystal structure of a complex between protein tyrosine phosphatase 1B and the insulin receptor tyrosine kinase. (PMID: 16271887) Li S. … Hubbard S.R. (Structure 2005) 3 4 22 64
  4. [Correlation between single nucleotide polymorphism of insulin receptor gene with polycystic ovary syndrome]. (PMID: 15498182) Chen Z.J. … Chang Z.H. (Zhonghua Fu Chan Ke Za Zhi 2004) 3 22 46 64
  5. Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2. (PMID: 10803466) Kasus-Jacobi A. … Burnol A.F. (Oncogene 2000) 3 4 22 64

Products for INSR Gene

Sources for INSR Gene

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