Interleukin 12 receptor, beta 1 subunit explained

Interleukin-12 receptor, beta 1, or IL-12Rβ1 in short, is a subunit of the interleukin 12 receptor and the interleukin 23 receptor. IL12RB1, is the name of its human gene.^[1] IL-12Rβ1 is also known as CD212 (cluster of differentiation 212).

The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily.

This protein binds to interleukin-12 (IL-12) with a low affinity, and is part of the IL-12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL-12 binding activity. The coexpression of this and IL-12Rβ2 protein was shown to lead to the formation of high-affinity IL-12 binding sites and reconstitution of IL-12 dependent signaling.

IL-12Rβ1 can also bind interleukin-23 (IL-23) as part of the IL-23 receptor complex. This complex forms a disulfide-linked oligomer, which is required for its IL-23 binding activity. The coexpression of this and IL-23R protein was shown to lead to the formation of IL-23 binding sites.

Various mutations in this gene were found to result in the immunodeficiency of patients with severe mycobacterial and Salmonella infections.^[2] Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.^[1]

All mutations known in the IL12RB1 gene, as well as many polymorphisms, have been collected in a mutation database ^{[3] [4]}

Further reading

• van de Vosse E, Lichtenauer-Kaligis EG, van Dissel JT, Ottenhoff TH . Genetic variations in the interleukin-12/interleukin-23 receptor (beta1) chain, and implications for IL-12 and IL-23 receptor structure and function . Immunogenetics . 54 . 12 . 817–29 . 2003 . 12671732 . 10.1007/s00251-002-0534-9 . 34119140 .
• Ling P, Gately MK, Gubler U, etal . Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity . J. Immunol. . 154 . 1 . 116–27 . 1995 . 10.4049/jimmunol.154.1.116 . 7527811 . free .
• Gillessen S, Carvajal D, Ling P, etal . Mouse interleukin-12 (IL-12) p40 homodimer: a potent IL-12 antagonist . Eur. J. Immunol. . 25 . 1 . 200–6 . 1995 . 7843232 . 10.1002/eji.1830250133 . 41702014 .
• Chua AO, Chizzonite R, Desai BB, etal . Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130 . J. Immunol. . 153 . 1 . 128–36 . 1994 . 10.4049/jimmunol.153.1.128 . 7911493 . 9211163 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Presky DH, Yang H, Minetti LJ, etal . A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits . Proc. Natl. Acad. Sci. U.S.A. . 93 . 24 . 14002–7 . 1997 . 8943050 . 10.1073/pnas.93.24.14002 . 19484 . free . 1996PNAS...9314002P .
• Gubler U, Presky DH . Molecular biology of interleukin-12 receptors . Ann. N. Y. Acad. Sci. . 795 . 36–40 . 1997 . 8958915 . 10.1111/j.1749-6632.1996.tb52653.x . 84507162 .
• Zou J, Presky DH, Wu CY, Gubler U . Differential associations between the cytoplasmic regions of the interleukin-12 receptor subunits beta1 and beta2 and JAK kinases . J. Biol. Chem. . 272 . 9 . 6073–7 . 1997 . 9038232 . 10.1074/jbc.272.9.6073 . free .
• Yamamoto K, Kobayashi H, Miura O, etal . Assignment of IL12RB1 and IL12RB2, interleukin-12 receptor beta 1 and beta 2 chains, to human chromosome 19 band p13.1 and chromosome 1 band p31.2, respectively, by in situ hybridization . Cytogenet. Cell Genet. . 77 . 3–4 . 257–8 . 1997 . 9284929 . 10.1159/000134589 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Igarashi O, Yamane H, Imajoh-Ohmi S, Nariuchi H . IL-12 receptor (IL-12R) expression and accumulation of IL-12R beta 1 and IL-12R beta 2 mRNAs in CD4+ T cells by costimulation with B7-2 molecules . J. Immunol. . 160 . 4 . 1638–46 . 1998 . 10.4049/jimmunol.160.4.1638 . 9469420 . free .
• de Jong R, Altare F, Haagen IA, etal . Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients . Science . 280 . 5368 . 1435–8 . 1998 . 9603733 . 10.1126/science.280.5368.1435 . 1998Sci...280.1435D .
• Kawashima T, Kawasaki H, Kitamura T, etal . Interleukin-12 induces tyrosine phosphorylation of an 85-kDa protein associated with the interleukin-12 receptor beta 1 subunit . Cell. Immunol. . 186 . 1 . 39–44 . 1998 . 9637763 . 10.1006/cimm.1998.1294 .
• Yao BB, Niu P, Surowy CS, Faltynek CR . Direct interaction of STAT4 with the IL-12 receptor . Arch. Biochem. Biophys. . 368 . 1 . 147–55 . 1999 . 10415122 . 10.1006/abbi.1999.1302 .
• Oppmann B, Lesley R, Blom B, etal . Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12 . Immunity . 13 . 5 . 715–25 . 2001 . 11114383 . 10.1016/S1074-7613(00)00070-4 . free .
• Altare F, Ensser A, Breiman A, etal . Interleukin-12 receptor beta1 deficiency in a patient with abdominal tuberculosis . J. Infect. Dis. . 184 . 2 . 231–6 . 2001 . 11424023 . 10.1086/321999 . free .
• Losana G, Rigamonti L, Borghi I, etal . Requirement for both IL-12 and IFN-gamma signaling pathways in optimal IFN-gamma production by human T cells . Eur. J. Immunol. . 32 . 3 . 693–700 . 2002 . 11857344 . 10.1002/1521-4141(200203)32:3<693::AID-IMMU693>3.0.CO;2-Q . 83984408 .
• Parham C, Chirica M, Timans J, etal . A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R . J. Immunol. . 168 . 11 . 5699–708 . 2002 . 12023369 . 10.4049/jimmunol.168.11.5699. free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Cleary AM, Tu W, Enright A, etal . Impaired accumulation and function of memory CD4 T cells in human IL-12 receptor beta 1 deficiency . J. Immunol. . 170 . 1 . 597–603 . 2003 . 12496448 . 10.4049/jimmunol.170.1.597. free .

Notes and References

1. Web site: Entrez Gene: IL12RB1 interleukin 12 receptor, beta 1.
2. Web site: OMIM Entry - # 614891 - IMMUNODEFICIENCY 30; IMD30. omim.org.
3. Web site: The IL12RB1 gene homepage - Global Variome shared LOVD.
4. 10.1002/humu.22380. 23864330. 4104692. IL-12Rβ1 Deficiency: Mutation Update and Description of theIL12RB1Variation Database. Human Mutation. 34. 10. 1329–1339. 2013. Van De Vosse. Esther. Haverkamp. Margje H. Ramirez-Alejo. Noe. Martinez-Gallo. Mónica. Blancas-Galicia. Lizbeth. Metin. Ayşe. Garty. Ben Zion. Sun-Tan. Çağman. Broides. Arnon. De Paus. Roelof A. Keskin. Özlem. Çağdaş. Deniz. Tezcan. Ilhan. Lopez-Ruzafa. Encarna. Aróstegui. Juan I. Levy. Jacov. Espinosa-Rosales. Francisco J. Sanal. Özden. Santos-Argumedo. Leopoldo. Casanova. Jean-Laurent. Boisson-Dupuis. Stephanie. Van Dissel. Jaap T. Bustamante. Jacinta.