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preproinsulin receptor; IR; CD220; contains: insulin receptor subunit alpha, insulin receptor subunit beta (INSR)

Function: - precursor for the insulin receptor - isoform short has a higher affinity for insulin - phosphorylation of Tyr-999 is required for IRS1- & SHC1- binding Structure: - contains both insulin receptor alpha & insulin receptor beta - after being transported from the endoplasmic reticulum to the Golgi apparatus, the single glycosylated precursor is further glycosylated & then cleaved, followed by its transport to the plasma membrane - belongs to the protein kinase superfamily, Tyr protein kinase family, insulin receptor subfamily - contains 2 fibronectin F3 modules - contains 1 protein kinase domain - sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition Compartment: membrane Alternative splicing: - named isoforms=2, long (HIR-B), short (HIR-A) Expression: - isoform long & isoform short are expressed in the peripheral nerve, kidney, liver, striated muscle, fibroblasts & skin - isoform short is expressed also in the spleen & lymphoblasts Pathology: - defects in INSR are the cause of a) insulin resistance b) Rabson-Mendenhall syndrome c) leprechaunism d) familial hyperinsulinemic hypoglycemia 5 e) insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) - defects in INSR may be associated with diabetes mellitus type 2

Related

insulin receptor; IR; (INSR)

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen protein precursor tyrosine kinase receptor (RTK)

Properties

SIZE: entity length = 1382 aa MW = 156 kD COMPARTMENT: cellular membrane STATE: active state MOTIF: signal sequence {1-27} N-glycosylation site {N43} N-glycosylation site {N52} N-glycosylation site {N105} N-glycosylation site {N138} cysteine-rich region {182-339} MOTIF: cysteine residue {C219} MODIFICATION: cysteine residue {C228} cysteine residue {C223} MODIFICATION: cysteine residue {C234} cysteine residue {C228} MODIFICATION: cysteine residue {C219} cysteine residue {C234} MODIFICATION: cysteine residue {C223} cysteine residue {C235} MODIFICATION: cysteine residue {C243} cysteine residue {C239} MODIFICATION: cysteine residue {C252} N-glycosylation site {N242} cysteine residue {C243} MODIFICATION: cysteine residue {C235} cysteine residue {C252} MODIFICATION: cysteine residue {C239} cysteine residue {C255} MODIFICATION: cysteine residue {C264} cysteine residue {C264} MODIFICATION: cysteine residue {C255} cysteine residue {C268} MODIFICATION: cysteine residue {C280} cysteine residue {C280} MODIFICATION: cysteine residue {C268} N-glycosylation site {N282} cysteine residue {C286} MODIFICATION: cysteine residue {C293} cysteine residue {C293} MODIFICATION: cysteine residue {C286} cysteine residue {C301} MODIFICATION: cysteine residue {C311} cysteine residue {C311} MODIFICATION: cysteine residue {C301} cysteine residue {C315} MODIFICATION: cysteine residue {C328} N-glycosylation site {N322} cysteine residue {C328} MODIFICATION: cysteine residue {C315} cysteine residue {C331} MODIFICATION: cysteine residue {C335} cysteine residue {C335} MODIFICATION: cysteine residue {C331} N-glycosylation site {N364} N-glycosylation site {N424} N-glycosylation site {N445} cysteine residue {C462} MODIFICATION: cysteine residue {C495} cysteine residue {C495} MODIFICATION: cysteine residue {C462} N-glycosylation site {N541} cysteine residue {C551} MODIFICATION: cysteine residue {C-INTERCHAIN} fibronectin type III domain or F3 module {618-847} MOTIF: N-glycosylation site {N633} N-glycosylation site {N651} N-glycosylation site {N698} N-glycosylation site {N769} N-glycosylation site {N782} fibronectin type III domain or F3 module {848-948} MOTIF: N-glycosylation site {N920} N-glycosylation site {N933} transmembrane domain {957-979} Tyr phosphorylation site {Y992} binding site SITE: 996-999 FOR-BINDING-OF: insulin receptor substrate 1 MOTIF: asparagine residue {996} proline residue {997} tyrosine residue {999} Tyr phosphorylation site {Y999} Tyr phosphorylation site {Y1011} kinase domain SITE: 1023-1298 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 1029-1037 ATP-binding site NAME: ATP-binding site SITE: 1057-1057 aspartate residue {D1159} Tyr phosphorylation site {Y1185} Tyr phosphorylation site {Y1189} Tyr phosphorylation site {Y1190} Tyr phosphorylation site {Y1355} binding site SITE: 1361-1364 FOR-BINDING-OF: PI-3-kinase p85 alpha MOTIF: Tyr phosphorylation site {Y1361}

Database Correlations

OMIM correlations MORBIDMAP 147670 UniProt P06213 PFAM correlations Kegg hsa:3643 ENZYME 2.7.10.1

References

  1. UniProt :accession P06213
  2. Wikipedia; Note: insulin receptor entry http://en.wikipedia.org/wiki/insulin_receptor
  3. Kemp BE, Pearson RB. Protein kinase recognition sequence motifs. Trends Biochem Sci. 1990 Sep;15(9):342-6. Review. PMID: 2238044
  4. Seino S, Seino M, Nishi S, Bell GI. Structure of the human insulin receptor gene and characterization of its promoter. Proc Natl Acad Sci U S A. 1989 Jan;86(1):114-8. PMID: 2911561