ID:I12R2_HUMAN DESCRIPTION: RecName: Full=Interleukin-12 receptor subunit beta-2; Short=IL-12 receptor subunit beta-2; Short=IL-12R subunit beta-2; Short=IL-12R-beta-2; Short=IL-12RB2; Flags: Precursor; FUNCTION: Receptor for interleukin-12. This subunit is the signaling component coupling to the JAK2/STAT4 pathway. Promotes the proliferation of T-cells as well as NK cells. Induces the promotion of T-cells towards the Th1 phenotype by strongly enhancing IFN-gamma production. SUBUNIT: Heterodimer/heterooligomer; disulfide-linked. The functional high affinity IL12 receptor is composed of I12RB1 and IL12RB2. Il12RB2 binds JAK2 (via its N-terminal) through a membrane-proximal region of the cytoplasmic domain. Interaction, in vitro and in vivo, with SOCS3 (via its SH2 domain) inhibits the STAT4-mediated activation. Binds STAT4 through a membrane-distal C-terminal region. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. TISSUE SPECIFICITY: Isoform 2 is expressed at similar levels in both naive and activated T-cells. DEVELOPMENTAL STAGE: Maximum levels in Th1 cells between day 3 and day 8 of activation. INDUCTION: In vitro, up-regulated by IFN-alpha. DOMAIN: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell- surface receptor binding. DOMAIN: The box 1 motif is required for JAK interaction and/or activation. PTM: On IL12 binding, phosphorylated on C-terminal tyrosine residues by JAK2. Phosphorylation on Tyr-800 is required for STAT4 binding and activation, and for SOCS3 binding. POLYMORPHISM: Heterozygotic variants Gly-313 and Arg-720 are associated with atopy, an immunological condition that can lead to clinical symptoms such as allergic rhinitis, sinusitis, asthma and eczema. SIMILARITY: Belongs to the type I cytokine receptor family. Type 2 subfamily. SIMILARITY: Contains 5 fibronectin type-III domains. WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/il12rb2/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00041 - Fibronectin type III domain PF06328 - Ig-like C2-type domain
SCOP Domains: 48726 - Immunoglobulin 49265 - Fibronectin type III
ModBase Predicted Comparative 3D Structure on Q99665
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004896 cytokine receptor activity GO:0019901 protein kinase binding
Biological Process: GO:0007166 cell surface receptor signaling pathway GO:0008284 positive regulation of cell proliferation GO:0018108 peptidyl-tyrosine phosphorylation GO:0032496 response to lipopolysaccharide GO:0032609 interferon-gamma production GO:0032729 positive regulation of interferon-gamma production GO:0034097 response to cytokine GO:0035722 interleukin-12-mediated signaling pathway GO:0070757 interleukin-35-mediated signaling pathway
Cellular Component: GO:0005886 plasma membrane GO:0005887 integral component of plasma membrane GO:0009897 external side of plasma membrane GO:0016020 membrane GO:0016021 integral component of membrane
Descriptions from all associated GenBank mRNAs
U64198 - Human Il-12 receptor beta2 mRNA, complete cds. AK294494 - Homo sapiens cDNA FLJ59237 complete cds, highly similar to Interleukin-12 receptor beta-2 chain precursor. AK316525 - Homo sapiens cDNA, FLJ79424 complete cds, highly similar to Interleukin-12 receptor beta-2 chain precursor. JD396251 - Sequence 377275 from Patent EP1572962. BC104772 - Homo sapiens interleukin 12 receptor, beta 2, mRNA (cDNA clone MGC:132432 IMAGE:8143775), complete cds. BC104774 - Homo sapiens interleukin 12 receptor, beta 2, mRNA (cDNA clone MGC:132434 IMAGE:8143777), complete cds. BC143248 - Homo sapiens cDNA clone IMAGE:9051750. BC143249 - Homo sapiens interleukin 12 receptor, beta 2, mRNA (cDNA clone MGC:176768 IMAGE:9051751), complete cds. BC143250 - Homo sapiens cDNA clone IMAGE:9051752. BC143252 - Homo sapiens cDNA clone IMAGE:9051754, containing frame-shift errors. JD292085 - Sequence 273109 from Patent EP1572962. KJ897052 - Synthetic construct Homo sapiens clone ccsbBroadEn_06446 IL12RB2 gene, encodes complete protein. KR712159 - Synthetic construct Homo sapiens clone CCSBHm_00036318 IL12RB2 (IL12RB2) mRNA, encodes complete protein. KR712160 - Synthetic construct Homo sapiens clone CCSBHm_00036319 IL12RB2 (IL12RB2) mRNA, encodes complete protein. AK300020 - Homo sapiens cDNA FLJ50202 complete cds, highly similar to Interleukin-12 receptor beta-2 chain precursor. AK310837 - Homo sapiens cDNA, FLJ17879. JD105445 - Sequence 86469 from Patent EP1572962. JD409528 - Sequence 390552 from Patent EP1572962. JD526873 - Sequence 507897 from Patent EP1572962. JD337258 - Sequence 318282 from Patent EP1572962. JD507488 - Sequence 488512 from Patent EP1572962. JD052415 - Sequence 33439 from Patent EP1572962. JD173936 - Sequence 154960 from Patent EP1572962. JD466921 - Sequence 447945 from Patent EP1572962. JD420931 - Sequence 401955 from Patent EP1572962. JD531594 - Sequence 512618 from Patent EP1572962. JD090856 - Sequence 71880 from Patent EP1572962. JD303391 - Sequence 284415 from Patent EP1572962. JD525036 - Sequence 506060 from Patent EP1572962. JD395745 - Sequence 376769 from Patent EP1572962. JD217785 - Sequence 198809 from Patent EP1572962. JD144491 - Sequence 125515 from Patent EP1572962. AK123656 - Homo sapiens cDNA FLJ41662 fis, clone FEBRA2027082.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_nktPathway - Selective expression of chemokine receptors during T-cell polarization h_IL12Pathway - IL12 and Stat4 Dependent Signaling Pathway in Th1 Development h_th1th2Pathway - Th1/Th2 Differentiation h_no2il12Pathway - NO2-dependent IL 12 Pathway in NK cells
Reactome (by CSHL, EBI, and GO)
Protein Q99665 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
