IL12 Active Protein

The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily. This protein binds to interleukine 12 (IL12) with a low affinity, and is thought to be a part of IL12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL12 binding activity. The coexpression of this and IL12RB2 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. Mutations in this gene impair the development of interleukin-17-producing T lymphocytes and result in increased susceptibility to mycobacterial and Salmonella infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

IL12RB1: Functions as an interleukin receptor which binds interleukin-12 with low affinity and is involved in IL12 transduction. Associated with IL12RB2 it forms a functional, high affinity receptor for IL12. Associates also with IL23R to form the interleukin-23 receptor which functions in IL23 signal transduction probably through activation of the Jak-Stat signaling cascade. Defects in IL12RB1 are a cause of mendelian susceptibility to mycobacterial disease (MSMD); also known as familial disseminated atypical mycobacterial infection. This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity, whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. Belongs to the type I cytokine receptor family. Type 2 subfamily. 3 isoforms of the human protein are produced by alternative splicing.

Protein type: Receptor, cytokine; Membrane protein, integral

Chromosomal Location of Human Ortholog: 19p13.1

Cellular Component: external side of plasma membrane

Molecular Function: hematopoietin/interferon-class (D200-domain) cytokine receptor activity; interleukin-12 receptor activity; interleukin-23 binding; interleukin-23 receptor activity; interleukin-12 receptor binding

Biological Process: positive regulation of memory T cell differentiation; positive regulation of interferon-gamma production; peptidyl-tyrosine phosphorylation; positive regulation of T-helper 1 type immune response; positive regulation of T cell mediated cytotoxicity; cytokine and chemokine mediated signaling pathway; positive regulation of defense response to virus by host; signal transduction; positive regulation of activated T cell proliferation

Disease: Immunodeficiency 30