Interleukin-23 receptor

IL23R
Identifiers
Aliases	IL23R, interleukin 23 receptor
External IDs	OMIM: 607562 MGI: 2181693 HomoloGene: 16930 GeneCards: IL23R
Gene location (Human)
Chr.	Chromosome 1 (human)[1]
End	67,259,979 bp[1]
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)[2]
End	67,491,855 bp[2]
Gene ontology
Molecular function	• interleukin-23 receptor activity; • interleukin-12 receptor binding; • GO:0001948 protein binding; • interleukin-23 binding; • cytokine receptor activity; • cytokine binding;
Cellular component	• integral component of membrane; • interleukin-23 receptor complex; • membrane; • receptor complex; • cell membrane; • external side of plasma membrane;
Biological process	• negative regulation of interleukin-10 production; • response to interferon-gamma; • positive regulation of interleukin-12 production; • immune system process; • positive regulation of T cell mediated cytotoxicity; • positive regulation of interferon-gamma production; • positive regulation of osteoclast differentiation; • positive regulation of T-helper 17 cell lineage commitment; • positive regulation of NK T cell activation; • positive regulation of natural killer cell proliferation; • response to lipopolysaccharide; • positive regulation of T-helper 17 type immune response; • positive regulation of T-helper 1 type immune response; • positive regulation of granulocyte macrophage colony-stimulating factor production; • defense response to Gram-negative bacterium; • positive regulation of T cell proliferation; • positive regulation of memory T cell differentiation; • positive regulation of interleukin-17 production; • innate immune system; • inflammatory response; • positive regulation of activated T cell proliferation; • positive regulation of defense response to virus by host; • positive regulation of activation of Janus kinase activity; • regulation of tyrosine phosphorylation of STAT protein; • positive regulation of tyrosine phosphorylation of STAT protein; • cytokine-mediated signaling pathway; • interleukin-23-mediated signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	149233
	209590
	ENSG00000162594
	ENSMUSG00000049093
	Q5VWK5
	Q8K4B4
	NM_144701
	NM_144548
	NP_653302
	NP_653131
	Wikidata
View/Edit Human	View/Edit Mouse

Interleukin-23 receptor is a type I cytokine receptor. IL23R is the name of its human gene.[5]

Function

The protein encoded by this gene is a subunit of the receptor for IL-23. This protein pairs with the receptor molecule IL-12Rβ1 (IL12RB1), together forming the IL-23 receptor complex, and both are required for IL-23 signaling. This protein associates constitutively with Janus kinase 2 (JAK2), and also binds to transcription activator STAT3 in a ligand-dependent manner.[5]

Structure

Crystal structure of human IL-23R (gold + pink) in complex with its cognate cytokine ligand IL-23 (marine blue and green).[6]

Clinical significance

Three variants in the IL23R gene have been shown to protect against Crohn's disease and ulcerative colitis.[7][8][9] The effect of IL-23R variations present in the population have been studied with an in vitro expression model system.[10]

Model organisms

Model organisms have been used in the study of IL23R function. A conditional knockout mouse line called Il23r^{tm2a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.[11] Male and female animals underwent a standardized phenotypic screen[12] to determine the effects of deletion.[13][14][15][16] Additional screens performed: - In-depth immunological phenotyping[17]

*Il23r* knockout mouse phenotype
Characteristic	Phenotype
All data available at.[12][17]
Peripheral blood leukocytes 6 Weeks	Normal
Insulin	Normal
Haematology 6 Weeks	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Normal

References

GRCh38: Ensembl release 89: ENSG00000162594 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000049093 - 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.
"Entrez Gene: IL23R interleukin 23 receptor".
Bloch Y, Bouchareychas L, Merceron R, Składanowska K, Van den Bossche L, Detry S, et al. (January 2018). "Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12Rβ1". Immunity. 48 (1): 45–58.e6. doi:10.1016/j.immuni.2017.12.008. PMID 29287995.
Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. (Dec 2006). "A genome-wide association study identifies IL23R as an inflammatory bowel disease gene". Science. 314 (5804): 1461–3. doi:10.1126/science.1135245. PMC 4410764. PMID 17068223.
Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, et al. (Nov 2011). "Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease". Nature Genetics. 43 (11): 1066–73. doi:10.1038/ng.952. PMC 3378381. PMID 21983784.
Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, Amininejad L, et al. (Jan 2011). "Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease". Nature Genetics. 43 (1): 43–7. doi:10.1038/ng.733. hdl:1854/LU-1145381. PMID 21151126.
de Paus RA, van de Wetering D, van Dissel JT, van de Vosse E (September 2008). "IL-23 and IL-12 responses in activated human T cells retrovirally transduced with IL-23 receptor variants". Molecular Immunology. 45 (15): 3889–95. doi:10.1016/j.molimm.2008.06.029. PMID 18675459.
Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
"International Mouse Phenotyping Consortium".
Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
"Infection and Immunity Immunophenotyping (3i) Consortium".

External links

Overview of all the structural information available in the PDB for UniProt: Q5VWK5 (Interleukin-23 receptor) at the PDBe-KB.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000162594 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000049093 - 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.

[entrez-5] "Entrez Gene: IL23R interleukin 23 receptor".

[6] Bloch Y, Bouchareychas L, Merceron R, Składanowska K, Van den Bossche L, Detry S, et al. (January 2018). "Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12Rβ1". Immunity. 48 (1): 45–58.e6. doi:10.1016/j.immuni.2017.12.008. PMID 29287995.

[7] Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. (Dec 2006). "A genome-wide association study identifies IL23R as an inflammatory bowel disease gene". Science. 314 (5804): 1461–3. doi:10.1126/science.1135245. PMC 4410764. PMID 17068223.

[8] Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, et al. (Nov 2011). "Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease". Nature Genetics. 43 (11): 1066–73. doi:10.1038/ng.952. PMC 3378381. PMID 21983784.

[9] Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, Amininejad L, et al. (Jan 2011). "Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease". Nature Genetics. 43 (1): 43–7. doi:10.1038/ng.733. hdl:1854/LU-1145381. PMID 21151126.

[pmid18675459-10] Paus RA, van de Wetering D, van Dissel JT, van de Vosse E (September 2008). "IL-23 and IL-12 responses in activated human T cells retrovirally transduced with IL-23 receptor variants". Molecular Immunology. 45 (15): 3889–95. doi:10.1016/j.molimm.2008.06.029. PMID 18675459.

[mgp_reference-11] Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.

[IMPCsearch_ref-12] "International Mouse Phenotyping Consortium".

[pmid21677750-13] Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-14] Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-15] Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.

[pmid23870131-16] White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, et al. (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.

[iii_ref-17] "Infection and Immunity Immunophenotyping (3i) Consortium".