IGF1R

Protein identityUniProt · HPA

UniProt accession

P08069

Gene

IGF1R

Ensembl

ENSG00000140443

Chromosome

15

Canonical length

1367 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, RAS pathway related proteins

Subcellular location

Nucleoli,Nucleoli rim,Plasma membrane,Primary cilium

OverviewNCBI Gene

This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

Canonical amino-acid sequenceUniProt

1367 residues, UniProt reviewed canonical sequence.

>P08069|IGF1R
     1  MKSGSGGGSP TSLWGLLFLS AALSLWPTSG EICGPGIDIR NDYQQLKRLE NCTVIEGYLH
    61  ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVIF
   121  EMTNLKDIGL YNLRNITRGA IRIEKNADLC YLSTVDWSLI LDAVSNNYIV GNKPPKECGD
   181  LCPGTMEEKP MCEKTTINNE YNYRCWTTNR CQKMCPSTCG KRACTENNEC CHPECLGSCS
   241  APDNDTACVA CRHYYYAGVC VPACPPNTYR FEGWRCVDRD FCANILSAES SDSEGFVIHD
   301  GECMQECPSG FIRNGSQSMY CIPCEGPCPK VCEEEKKTKT IDSVTSAQML QGCTIFKGNL
   361  LINIRRGNNI ASELENFMGL IEVVTGYVKI RHSHALVSLS FLKNLRLILG EEQLEGNYSF
   421  YVLDNQNLQQ LWDWDHRNLT IKAGKMYFAF NPKLCVSEIY RMEEVTGTKG RQSKGDINTR
   481  NNGERASCES DVLHFTSTTT SKNRIIITWH RYRPPDYRDL ISFTVYYKEA PFKNVTEYDG
   541  QDACGSNSWN MVDVDLPPNK DVEPGILLHG LKPWTQYAVY VKAVTLTMVE NDHIRGAKSE
   601  ILYIRTNASV PSIPLDVLSA SNSSSQLIVK WNPPSLPNGN LSYYIVRWQR QPQDGYLYRH
   661  NYCSKDKIPI RKYADGTIDI EEVTENPKTE VCGGEKGPCC ACPKTEAEKQ AEKEEAEYRK
   721  VFENFLHNSI FVPRPERKRR DVMQVANTTM SSRSRNTTAA DTYNITDPEE LETEYPFFES
   781  RVDNKERTVI SNLRPFTLYR IDIHSCNHEA EKLGCSASNF VFARTMPAEG ADDIPGPVTW
   841  EPRPENSIFL KWPEPENPNG LILMYEIKYG SQVEDQRECV SRQEYRKYGG AKLNRLNPGN
   901  YTARIQATSL SGNGSWTDPV FFYVQAKTGY ENFIHLIIAL PVAVLLIVGG LVIMLYVFHR
   961  KRNNSRLGNG VLYASVNPEY FSAADVYVPD EWEVAREKIT MSRELGQGSF GMVYEGVAKG
  1021  VVKDEPETRV AIKTVNEAAS MRERIEFLNE ASVMKEFNCH HVVRLLGVVS QGQPTLVIME
  1081  LMTRGDLKSY LRSLRPEMEN NPVLAPPSLS KMIQMAGEIA DGMAYLNANK FVHRDLAARN
  1141  CMVAEDFTVK IGDFGMTRDI YETDYYRKGG KGLLPVRWMS PESLKDGVFT TYSDVWSFGV
  1201  VLWEIATLAE QPYQGLSNEQ VLRFVMEGGL LDKPDNCPDM LFELMRMCWQ YNPKMRPSFL
  1261  EIISSIKEEM EPGFREVSFY YSEENKLPEP EELDLEPENM ESVPLDPSAS SSSLPLPDRH
  1321  SGHKAENGPG PGVLVLRASF DERQPYAHMN GGRKNERALP LPQSSTC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IGF1R can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

19 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IGF1R.

Disease | AllUniProt

Conditions IGF1R is implicated in, by any mechanism.

• Insulin-like growth factor 1 resistance (IGF1RES) MIM:270450

Disease | GeneticClinVar

78 pathogenic / likely-pathogenic of 1,344 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Growth delay due to insulin-like growth factor I resistance
• Inborn genetic diseases
• Neurodevelopmental disorder
• IGF1R-related disorder
• Intellectual disability

Disease | AutoantibodyPubMed

Conditions in which antibodies against IGF1R are reported. Each links to that disease's full target list.

• Graves Disease 3

Showing 1 of 2 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for IGF1R from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.31

gnomAD pLI

0.97

gnomAD missense Z

2.73

DepMap mean gene effect

-0.31

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amyloid-beta clearance
• cellular response to amyloid-beta
• cellular response to glucose stimulus
• dendritic spine maintenance
• immune response
• insulin receptor signaling pathway
• insulin-like growth factor receptor signaling pathway
• negative regulation of apoptotic process
• negative regulation of MAPK cascade
• peptidyl-tyrosine autophosphorylation
• phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of cell migration
• positive regulation of cell population proliferation
• positive regulation of cold-induced thermogenesis
• positive regulation of MAPK cascade
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of protein-containing complex disassembly
• protein autophosphorylation
• regulation of JNK cascade
• signal transduction
• transcytosis

Molecular functions

• ATP binding
• identical protein binding
• insulin binding
• insulin receptor activity
• insulin receptor binding
• insulin receptor substrate binding
• insulin-like growth factor binding
• insulin-like growth factor I binding
• insulin-like growth factor receptor activity
• phosphatidylinositol 3-kinase binding
• protein transporter activity
• protein tyrosine kinase activity

Cellular components

• alphav-beta3 integrin-IGF-1-IGF1R complex
• axon
• cilium
• insulin receptor complex
• membrane
• nucleolus
• plasma membrane
• protein kinase complex
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Receptor L-domain
• Protein kinase domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Tyrosine-protein kinase, receptor class II, conserved site
• Fibronectin type III
• Furin-like cysteine-rich domain
• Furin-like repeat
• Tyrosine-protein kinase, active site
• Growth factor receptor cysteine-rich domain superfamily
• Protein kinase-like domain superfamily
• Immunoglobulin-like fold
• Tyrosine-protein kinase, insulin-like receptor
• Protein kinase, ATP binding site
• Tyrosine-protein kinase, catalytic domain
• Fibronectin type III superfamily
• Receptor L-domain superfamily
• Receptor Tyrosine Kinase
• Furin-like cysteine rich region
• Receptor L domain
• Protein tyrosine and serine/threonine kinase

KeywordsUniProt

• ATP-binding
• Cell membrane
• Cleavage on pair of basic residues
• Disulfide bond
• Glycoprotein
• Host-virus interaction
• Isopeptide bond
• Kinase
• Membrane
• Nucleotide-binding
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transferase
• Transmembrane
• Transmembrane helix
• Tyrosine-protein kinase
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of IGF1R in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARRB1
• ARRB2
• GRB10
• MAP3K5
• NMD2
• PIK3R1
• RACK1
• SHC1
• SOCS1
• SOCS2
• SOCS3
• STAT3
• SH2B1
• ZFAND2B
• MDM2
• ARHGEF12
• CANX
• CSK
• INSR
• PIK3R2
• PIK3R3
• PPM1A
• PTPN1
• PTPN11
• PTPN6
• SDF2L1
• YWHAE
• YWHAG