INSRR

INSRR
Identifiers
Aliases	INSRR, IRR, insulin receptor related receptor
External IDs	OMIM: 147671; MGI: 1346037; GeneCards: INSRR
Enzyme activity
Gene location (Human)
Chr.	Chromosome 1 (human)
End	156,859,117 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	87,723,408 bp
RNA expression pattern
	Top expressed in
	body of stomach; ; human kidney; ; body of uterus; ; right testis; ; apex of heart; ; myometrium; ; canal of the cervix; ; fundus; ; left testis; ; abdominal wall;
	Top expressed in
	islet of Langerhans; ; right kidney; ; cingulate gyrus; ; embryo; ; internal carotid artery; ; external carotid artery; ; central gray substance of midbrain; ; glossopharyngeal ganglion; ; nucleus of stria terminalis; ; human kidney;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	transmembrane receptor protein tyrosine kinase activity; phosphatidylinositol 3-kinase binding; insulin receptor substrate binding; nucleotide binding; protein kinase activity; protein tyrosine kinase activity; transferase activity; ATP binding; kinase activity; receptor tyrosine kinase; transmembrane signaling receptor activity; insulin-activated receptor activity;
Cellular component	receptor complex; integral component of membrane; integral component of plasma membrane; membrane; cytoplasm; insulin receptor complex; axon;
Biological process	actin cytoskeleton reorganization; protein autophosphorylation; protein phosphorylation; cellular response to alkaline pH; male sex determination; phosphorylation; transmembrane receptor protein tyrosine kinase signaling pathway; peptidyl-tyrosine phosphorylation; insulin receptor signaling pathway; negative regulation of signal transduction; cell differentiation; glucose homeostasis; negative regulation of apoptotic process; positive regulation of ERK1 and ERK2 cascade; anatomical structure development;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	3645
	23920
	ENSG00000027644
	ENSMUSG00000005640
	P14616
	Q9WTL4
	NM_014215
	NM_011832
	NP_055030
	NP_035962
	Wikidata
View/Edit Human	View/Edit Mouse

Insulin receptor-related protein is a protein that in humans is encoded by the INSRR gene.

Function

The encoded protein, commonly abbreviated IRR, is an orphan receptor and one of three receptor tyrosine kinases in the insulin receptor family, alongside the insulin receptor and insulin-like growth factor 1 receptor. No endogenous peptide or protein ligand is known for IRR. In experimental systems, extracellular pH above approximately 7.9 activates the receptor and triggers autophosphorylation.

The Human Protein Atlas classifies INSRR RNA expression as cell type enhanced in renal collecting-duct intercalated cells. In rodents, IRR has been localized to non-A intercalated cells; a rat study reported basolateral localization in type B intercalated cells of the cortical collecting duct. In mice, inactivation of Insrr impairs urinary bicarbonate excretion following alkali loading, supporting a role for the receptor in renal acid–base homeostasis.

A 2023 cryo-electron microscopy study of the human IRR ectodomain, combined with mutagenesis and cell-based assays, supported a model in which alkaline pH produces electrostatic repulsion involving pH-sensitive motifs at an interprotomer interface, disrupting the autoinhibited state and promoting a scissor-like rotation into a T-shaped active conformation.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000027644 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000005640 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Shier P, Watt VM (5 September 1989). "Primary structure of a putative receptor for a ligand of the insulin family". J Biol Chem. 264 (25): 14605–8. doi:10.1016/S0021-9258(18)63737-8. PMID 2768234.
↑ Shier P, Willard HF, Watt VM (1990). "Localization of the insulin receptor-related receptor gene to human chromosome 1". Cytogenet Cell Genet. 54 (1–2): 80–1. doi:10.1159/000132963. PMID 2249481.
↑ "Entrez Gene: INSRR insulin receptor-related receptor".
↑ Petrenko AG, Zozulya SA, Deyev IE, Eladari D (October 2013). "Insulin receptor-related receptor as an extracellular pH sensor involved in the regulation of acid–base balance". Biochim. Biophys. Acta. 1834 (10): 2170–2175. doi:10.1016/j.bbapap.2012.11.011. PMID 23220417.
1 2 Deyev IE, Sohet F, Vassilenko KP, Serova OV, Popova NV, Zozulya SA, et al. (June 2011). "Insulin receptor-related receptor as an extracellular alkali sensor". Cell Metab. 13 (6): 679–689. doi:10.1016/j.cmet.2011.03.022. PMC 3119365. PMID 21641549.
↑ "INSRR – Single cell type". The Human Protein Atlas. Retrieved 30 July 2026.
↑ Bates CM, Merenmies JM, Kelly-Spratt KS, Parada LF (September 1997). "Insulin receptor-related receptor expression in non-A intercalated cells in the kidney". Kidney Int. 52 (3): 674–681. doi:10.1038/ki.1997.381. PMID 9291186.
↑ Ozaki K, Takada N, Tsujimoto K, Tsuji N, Kawamura T, Muso E, Ohta M, Itoh N (September 1997). "Localization of insulin receptor-related receptor in the rat kidney". Kidney Int. 52 (3): 694–698. doi:10.1038/ki.1997.384. PMID 9291189.
↑ Brown D, Wagner CA (May 2012). "Molecular mechanisms of acid-base sensing by the kidney". J. Am. Soc. Nephrol. 23 (5): 774–780. doi:10.1681/ASN.2012010029. PMC 3338302. PMID 22362904.
↑ Wang L, Hall C, Li J, Choi E, Bai XC (May 2023). "Structural basis of the alkaline pH-dependent activation of insulin receptor-related receptor". Nat. Struct. Mol. Biol. 30 (5): 661–669. doi:10.1038/s41594-023-00974-0. PMC 10465182. PMID 37055497.

Zhang B, Roth RA (1992). "The insulin receptor-related receptor. Tissue expression, ligand binding specificity, and signaling capabilities". J. Biol. Chem. 267 (26): 18320–8. doi:10.1016/S0021-9258(19)36963-7. PMID 1326521.
Mathi SK, Chan J, Watt VM (1995). "Insulin receptor-related receptor messenger ribonucleic acid: quantitative distribution and localization to subpopulations of epithelial cells in stomach and kidney". Endocrinology. 136 (9): 4125–32. doi:10.1210/endo.136.9.7649121. PMID 7649121.
Kovacina KS, Roth RA (1995). "Characterization of the endogenous insulin receptor-related receptor in neuroblastomas". J. Biol. Chem. 270 (4): 1881–7. doi:10.1074/jbc.270.4.1881. PMID 7829525.
Jui HY, Accili D, Taylor SI (1996). "Characterization of a hybrid receptor formed by dimerization of the insulin receptor-related receptor (IRR) with the insulin receptor (IR): coexpression of cDNAs encoding human IRR and human IR in NIH-3T3 cells". Biochemistry. 35 (45): 14326–30. doi:10.1021/bi9613032. PMID 8916919.
Hänze J, Berthold A, Klammt J, Gallaher B, Siebler T, Kratzsch J, Elmlinger M, Kiess W (1999). "Cloning and sequencing of the complete cDNA encoding the human insulin receptor related receptor". Horm. Metab. Res. 31 (2–3): 77–9. doi:10.1055/s-2007-978702. PMID 10226785. S2CID 260167556.
Xu P, Jacobs AR, Taylor SI (1999). "Interaction of insulin receptor substrate 3 with insulin receptor, insulin receptor-related receptor, insulin-like growth factor-1 receptor, and downstream signaling proteins". J. Biol. Chem. 274 (21): 15262–70. doi:10.1074/jbc.274.21.15262. PMID 10329736.
Elmlinger MW, Rauschnabel U, Koscielniak E, Haenze J, Ranke MB, Berthold A, Klammt J, Kiess W (1999). "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". Regul. Pept. 84 (1–3): 37–42. doi:10.1016/S0167-0115(99)00065-8. PMID 10535406. S2CID 664805.
Whitmore TE, Maurer MF, Day HL, Jelmberg AC, Dasovich MM, Sundborg LM, Burkhead SK, Heipel MD, Madden KL, et al. (1999). "The assignment of the human insulin receptor-related receptor gene (INSRR) to chromosome 1q21→q23 by the use of radiation hybrid mapping". Cytogenet. Cell Genet. 87 (1–2): 93–4. doi:10.1159/000015400. PMID 10640820. S2CID 36476566.
Weber A, Huesken C, Bergmann E, Kiess W, Christiansen NM, Christiansen H (2003). "Coexpression of insulin receptor-related receptor and insulin-like growth factor 1 receptor correlates with enhanced apoptosis and dedifferentiation in human neuroblastomas". Clin. Cancer Res. 9 (15): 5683–92. PMID 14654552.
Klammt J, Garten A, Barnikol-Oettler A, Beck-Sickinger AG, Kiess W (2005). "Comparative analysis of the signaling capabilities of the insulin receptor-related receptor". Biochem. Biophys. Res. Commun. 327 (2): 557–64. Bibcode:2005BBRC..327..557K. doi:10.1016/j.bbrc.2004.12.039. PMID 15629149.
Dissen GA, Garcia-Rudaz C, Tapia V, Parada LF, Hsu SY, Ojeda SR (2006). "Expression of the insulin receptor-related receptor is induced by the preovulatory surge of luteinizing hormone in thecal-interstitial cells of the rat ovary". Endocrinology. 147 (1): 155–65. doi:10.1210/en.2005-0386. PMID 16195402.

This article on a gene on human chromosome 1 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000027644 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000005640 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid2768234-5] Shier P, Watt VM (5 September 1989). "Primary structure of a putative receptor for a ligand of the insulin family". J Biol Chem. 264 (25): 14605–8. doi:10.1016/S0021-9258(18)63737-8. PMID 2768234.

[pmid2249481-6] Shier P, Willard HF, Watt VM (1990). "Localization of the insulin receptor-related receptor gene to human chromosome 1". Cytogenet Cell Genet. 54 (1–2): 80–1. doi:10.1159/000132963. PMID 2249481.

[entrez-7] "Entrez Gene: INSRR insulin receptor-related receptor".

[Petrenko2013-8] Petrenko AG, Zozulya SA, Deyev IE, Eladari D (October 2013). "Insulin receptor-related receptor as an extracellular pH sensor involved in the regulation of acid–base balance". Biochim. Biophys. Acta. 1834 (10): 2170–2175. doi:10.1016/j.bbapap.2012.11.011. PMID 23220417.

[Deyev2011-9] 1 2 Deyev IE, Sohet F, Vassilenko KP, Serova OV, Popova NV, Zozulya SA, et al. (June 2011). "Insulin receptor-related receptor as an extracellular alkali sensor". Cell Metab. 13 (6): 679–689. doi:10.1016/j.cmet.2011.03.022. PMC 3119365. PMID 21641549.

[HPA-10] "INSRR – Single cell type". The Human Protein Atlas. Retrieved 30 July 2026.

[Bates1997-11] Bates CM, Merenmies JM, Kelly-Spratt KS, Parada LF (September 1997). "Insulin receptor-related receptor expression in non-A intercalated cells in the kidney". Kidney Int. 52 (3): 674–681. doi:10.1038/ki.1997.381. PMID 9291186.

[Ozaki1997-12] Ozaki K, Takada N, Tsujimoto K, Tsuji N, Kawamura T, Muso E, Ohta M, Itoh N (September 1997). "Localization of insulin receptor-related receptor in the rat kidney". Kidney Int. 52 (3): 694–698. doi:10.1038/ki.1997.384. PMID 9291189.

[BrownWagner2012-13] Brown D, Wagner CA (May 2012). "Molecular mechanisms of acid-base sensing by the kidney". J. Am. Soc. Nephrol. 23 (5): 774–780. doi:10.1681/ASN.2012010029. PMC 3338302. PMID 22362904.

[Wang2023-14] Wang L, Hall C, Li J, Choi E, Bai XC (May 2023). "Structural basis of the alkaline pH-dependent activation of insulin receptor-related receptor". Nat. Struct. Mol. Biol. 30 (5): 661–669. doi:10.1038/s41594-023-00974-0. PMC 10465182. PMID 37055497.

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

INSRR

Function

References

Further reading