Interleukin-12 subunit beta

Interleukin-12 subunit beta
Interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40)

PDB rendering based on 1f42.
Identifiers
Symbols IL12B; CLMF; CLMF2; IL-12B; NKSF; NKSF2
External IDs OMIM161561 MGI96540 HomoloGene1648 GeneCards: IL12B Gene
RNA expression pattern
PBB GE IL12B 207901 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3593 16160
Ensembl ENSG00000113302 ENSMUSG00000004296
UniProt P29460 Q3ZAX5
RefSeq (mRNA) NM_002187.2 NM_008352.2
RefSeq (protein) NP_002178.2 NP_032378.1
Location (UCSC) Chr 5:
158.74 – 158.76 Mb
Chr 11:
44.21 – 44.23 Mb
PubMed search [1] [2]

Subunit beta of interleukin 12 (also known as natural killer cell stimulatory factor 2, or cytotoxic lymphocyte maturation factor 2, p40) (human gene name IL12B) is a subunit of human interleukin 12.

This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter gene polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children.[1]

Contents

Interactions

Interleukin-12 subunit beta has been shown to interact with Interleukin 23.[2]

RNA editing

Interleukin 12 receptor, beta 2 subunit(IL12Rβ2) is a product of the IL12-R β2 gene.As previously mentioned the gene product is one of two subunits which combine to form the IL-12 receptor.The other subunit being IL12-R β1 subunit.[3] The β2 subunit is only expressed in Th1 lymphocytes.The pre-mRNA of the IL12-R β2 gene is subject to RNA editing.

Editing type

Cytidine to Uridine (C to U) RNA editing.

Editing sites

The editing site is located at nucleotide 2451 which is found in exon 13 which forms part of the extracellular domain of the protein.[4] However another report was unable to detect this C to U conversion[5]

Effects of RNA editing

Protein structure

Editng results in an amino acid change fro an alanine to a valine may cause a conformational change in the IL12 receptor.[4]

Protein function

Edting causes a reduction in the extent of IL-12 signalling as the β subunit is involved in signal transduction.This leads to insufficient IFN-γ production possibly due to an interruption of the binding of IL12 to its receptor.Binding may be restricyed due to a conformational change caused by the change of amino acid.The change in the signalling cascade and reduction of IFN-γ effects downregulation of IgE. Atrophy patients have enhanced IgE sensitivity to everyday environmental factors such as asthma.This is the only editing event linked to atrophy.[4]

Associated conditions

There is an increase in the frequency of editing in Atopic patients (20.6%) from that non atopic patients (3.8%) transcripts.This is the first reported case that indicates that atopy could be associated with RNA editing.Atopy is characterized by enhanced immunoglobulin E (IgE) responses to common environmental antigens and leads to clinical disorders such as asthma, eczema and rhinitis. [4]

References

  1. ^ "Entrez Gene: IL12B interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3593. 
  2. ^ Oppmann, B; Lesley R, Blom B, Timans J C, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams J S, Moore K W, Rennick D, de Waal-Malefyt R, Hannum C, Bazan J F, Kastelein R A (Nov. 2000). "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12". Immunity (UNITED STATES) 13 (5): 715–25. doi:10.1016/S1074-7613(00)00070-4. ISSN 1074-7613. PMID 11114383. 
  3. ^ Presky DH, Yang H, Minetti LJ, et al. (November 1996). "A functional interleukin 12 receptor complex is composed of two β-type cytokine receptor subunits". Proc. Natl. Acad. Sci. U.S.A. 93 (24): 14002–7. doi:10.1073/pnas.93.24.14002. PMC 19484. PMID 8943050. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=8943050. 
  4. ^ a b c d Kondo N, Matsui E, Kaneko H, et al. (March 2004). "RNA editing of interleukin-12 receptor beta2, 2451 C-to-U (Ala 604 Val) conversion, associated with atopy". Clin. Exp. Allergy 34 (3): 363–8. doi:10.1111/j.1365-2222.2004.01901.x. PMID 15005728. http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-7894&date=2004&volume=34&issue=3&spage=363. 
  5. ^ Kim EJ, Lee WM, Ha JS, Ryoo NH, Jeon DS, Kim JR (December 2006). "mRNA Expression and RNA Editing (2451 C-to-U) of IL-12 Receptor β2 in Adult Atopic Patients". J. Korean Med. Sci. 21 (6): 1070–4. doi:10.3346/jkms.2006.21.6.1070. PMC 2721931. PMID 17179689. http://jkms.org/DOIx.php?id=10.3346/jkms.2006.21.6.1070. 

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