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Gene Review

INSRR  -  insulin receptor-related receptor

Homo sapiens

Synonyms: IR-related receptor, IRR, Insulin receptor-related protein
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Disease relevance of INSRR


Psychiatry related information on INSRR

  • Having an incontinent wife put men at greater risk for depressive symptoms (unadj. IRR = 1.13, 95% CIs = 1.02, 1.25), although this relation became nonsignificant with the addition of control variables [6].
  • MLU for IRR speech was greater than that for productive utterances, which supports the idea that these productions facilitate language development [7].

High impact information on INSRR

  • IS911 transposition occurs in several steps: synapsis of the two transposon ends (IRR and IRL); formation of a figure-of-eight intermediate where both ends are joined by a single-strand bridge; resolution into a circular form carrying an IRR-IRL junction; and insertion into a DNA target [8].
  • The C-terminal domain of IRRR was found to abolish binding in IR and IGFIR context, whereas other constructs bound ligands [9].
  • Increased tyrosine phosphorylation of these proteins is also observed in cells expressing a transforming chicken c-Src (mutant Phe-527) and in cells with the activated tyrosine kinase domains of the Drosophila insulin receptor, human insulin-like growth factor I receptor, and human insulin receptor-related receptor [10].
  • Characterization of the endogenous insulin receptor-related receptor in neuroblastomas [11].
  • The intrinsic tyrosine kinase activity of this endogenous IRR was activated by the agonist monoclonal antibody to IRR but not by nerve growth factor, insulin-like growth factor I, or insulin [11].

Chemical compound and disease context of INSRR


Biological context of INSRR


Anatomical context of INSRR


Associations of INSRR with chemical compounds

  • Our data suggest an influence of IRR on IGF signaling via IGF-1R because coexpression of these two receptor tyrosine kinases was significantly correlated with an undifferentiated histology, a high AI, and an advanced survival probability [1].
  • Phosphotyrosine detection revealed a lack in the constitutive activation of the IRR described for analogous constructs of the two other members of the family [15].
  • We conclude that INSRR has no detectable mutations contributing to diabetes in the Pima Indians [13].
  • Binding properties of chimeric insulin receptors containing the cysteine-rich domain of either the insulin-like growth factor I receptor or the insulin receptor related receptor [18].
  • Expression of the insulin receptor-related receptor is induced by the preovulatory surge of luteinizing hormone in thecal-interstitial cells of the rat ovary [19].

Regulatory relationships of INSRR


Other interactions of INSRR

  • CONCLUSION: IRR expression is a new marker for a favorable prognosis in neuroblastoma that is independent of MYCN amplification and age at diagnosis [1].
  • In particular, the mRNA levels of IRR and IGF-I-R were compared by semi-quantitative RT-PCR in seven neuroblastomas and 11 soft tissue sarcomas (STS), five of which were of neuronal origin [2].
  • We amplified human kidney IRR by the polymerase chain reaction to quantitate the proportion of transcripts which included the 24-nucleotide sequence between exons 13 and 14 [16].
  • In contrast, chimeric receptors containing exon 3 of IRR did not bind either IGF-I, IGF-II, or relaxin [18].

Analytical, diagnostic and therapeutic context of INSRR

  • In the present work, we investigated the potential of the third member of the family, insulin receptor-related receptor (IRR), to associate with known interaction partners of the InsR and the IGF-I receptor in a yeast two-hybrid assay [15].
  • In situ hybridization histochemical analysis revealed that IRR transcripts were present in a subpopulation of cells within distal tubules of human kidney, beyond the most proximal segment of the distal convoluted tubule [20].
  • An extensive molecular search using several approaches, including the screening of cDNA libraries and PCR amplification with degenerate primers, did not yield an IRR ligand [19].
  • In women with Quetelet's index equal to or greater than 24 there was a positive relation between coffee intake and breast cancer risk (chi 2 trend = 2.33, P = 0.13), where the corresponding age-adjusted IRR was 2.1 (95% confidence intervals, 0.8 and 5.2) [21].
  • RESULTS: In the cohort analyses, risk of depression was significantly higher in men with BPH compared to those without (IRR 2.17, 2.12-2.22), but was not significantly different for men exposed to alpha 1-blockers versus those unexposed when adjusted for the presence of BPH [22].


  1. Coexpression of insulin receptor-related receptor and insulin-like growth factor 1 receptor correlates with enhanced apoptosis and dedifferentiation in human neuroblastomas. Weber, A., Huesken, C., Bergmann, E., Kiess, W., Christiansen, N.M., Christiansen, H. Clin. Cancer Res. (2003) [Pubmed]
  2. Correlation of type I insulin-like growth factor receptor (IGF-I-R) and insulin receptor-related receptor (IRR) messenger RNA levels in tumor cell lines from pediatric tumors of neuronal origin. Elmlinger, M.W., Rauschnabel, U., Koscielniak, E., Haenze, J., Ranke, M.B., Berthold, A., Klammt, J., Kiess, W. Regul. Pept. (1999) [Pubmed]
  3. Insulin receptor-related receptor messenger ribonucleic acid is focally expressed in sympathetic and sensory neurons and renal distal tubule cells. Reinhardt, R.R., Chin, E., Zhang, B., Roth, R.A., Bondy, C.A. Endocrinology (1993) [Pubmed]
  4. Gene expression and tyrosine kinase activity of insulin receptor in uterine leiomyoma and matched myometrium. Toscani, G.K., Chaves, E.M., Cervi, F.L., Tavares, M.B., Silva, I.S., von Eye Corleta, H., Capp, E. Arch. Gynecol. Obstet. (2004) [Pubmed]
  5. Multiple births, sex of children and subsequent breast-cancer risk for the mothers: a prospective study in Norway. Albrektsen, G., Heuch, I., Kvåle, G. Int. J. Cancer (1995) [Pubmed]
  6. The impact of own and spouse's urinary incontinence on depressive symptoms. Fultz, N.H., Rahrig Jenkins, K., Østbye, T., Taylor, D.H., Kabeto, M.U., Langa, K.M. Social science & medicine (1982) (2005) [Pubmed]
  7. Imitations, repetitions, routines, and the child's analysis of language: insights from the blind. Pérez-Pereira, M. Journal of child language. (1994) [Pubmed]
  8. A target specificity switch in IS911 transposition: the role of the OrfA protein. Loot, C., Turlan, C., Rousseau, P., Ton-Hoang, B., Chandler, M. EMBO J. (2002) [Pubmed]
  9. Specificity of insulin and insulin-like growth factor I receptors investigated using chimeric mini-receptors. Role of C-terminal of receptor alpha subunit. Kristensen, C., Wiberg, F.C., Andersen, A.S. J. Biol. Chem. (1999) [Pubmed]
  10. Characterization and cloning of a 58/53-kDa substrate of the insulin receptor tyrosine kinase. Yeh, T.C., Ogawa, W., Danielsen, A.G., Roth, R.A. J. Biol. Chem. (1996) [Pubmed]
  11. Characterization of the endogenous insulin receptor-related receptor in neuroblastomas. Kovacina, K.S., Roth, R.A. J. Biol. Chem. (1995) [Pubmed]
  12. Dietary intake of folic acid and colorectal cancer risk in a cohort of women. Terry, P., Jain, M., Miller, A.B., Howe, G.R., Rohan, T.E. Int. J. Cancer (2002) [Pubmed]
  13. Polymorphism screening of the insulin receptor-related receptor gene (INSRR) on 1q in Pima Indians. Wolford, J.K., Thameem, F., Bogardus, C., Prochazka, M. Mol. Cell. Probes (2001) [Pubmed]
  14. The assignment of the human insulin receptor-related receptor gene (INSRR) to chromosome 1q21-->q23 by the use of radiation hybrid mapping. Whitmore, T.E., Maurer, M.F., Day, H.L., Jelmberg, A.C., Dasovich, M.M., Sundborg, L.M., Burkhead, S.K., Heipel, M.D., Madden, K.L., Kramer, J.M., Kuijper, J.L., Xu, W.F., Jaspers, S.R., Holly, R.D., Lok, S. Cytogenet. Cell Genet. (1999) [Pubmed]
  15. Comparative analysis of the signaling capabilities of the insulin receptor-related receptor. Klammt, J., Garten, A., Barnikol-Oettler, A., Beck-Sickinger, A.G., Kiess, W. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  16. Expression of a cDNA encoding the human insulin receptor-related receptor. Jui, H.Y., Suzuki, Y., Accili, D., Taylor, S.I. J. Biol. Chem. (1994) [Pubmed]
  17. The insulin receptor-related receptor. Tissue expression, ligand binding specificity, and signaling capabilities. Zhang, B., Roth, R.A. J. Biol. Chem. (1992) [Pubmed]
  18. Binding properties of chimeric insulin receptors containing the cysteine-rich domain of either the insulin-like growth factor I receptor or the insulin receptor related receptor. Zhang, B., Roth, R.A. Biochemistry (1991) [Pubmed]
  19. Expression of the insulin receptor-related receptor is induced by the preovulatory surge of luteinizing hormone in thecal-interstitial cells of the rat ovary. Dissen, G.A., Garcia-Rudaz, C., Tapia, V., Parada, L.F., Hsu, S.Y., Ojeda, S.R. Endocrinology (2006) [Pubmed]
  20. Insulin receptor-related receptor messenger ribonucleic acid: quantitative distribution and localization to subpopulations of epithelial cells in stomach and kidney. Mathi, S.K., Chan, J., Watt, V.M. Endocrinology (1995) [Pubmed]
  21. Coffee consumption and the risk of breast cancer. A prospective study of 14,593 Norwegian women. Vatten, L.J., Solvoll, K., Løken, E.B. Br. J. Cancer (1990) [Pubmed]
  22. Drug or symptom-induced depression in men treated with alpha 1-blockers for benign prostatic hyperplasia? A nested case-control study. Clifford, G.M., Farmer, R.D. Pharmacoepidemiology and drug safety. (2002) [Pubmed]
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