I12R2_MOUSE
ID I12R2_MOUSE Reviewed; 874 AA.
AC P97378; B9EHD9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Interleukin-12 receptor subunit beta-2;
DE Short=IL-12 receptor subunit beta-2;
DE Short=IL-12R subunit beta-2;
DE Short=IL-12R-beta-2;
DE Short=IL-12RB2;
DE Flags: Precursor;
GN Name=Il12rb2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8943050; DOI=10.1073/pnas.93.24.14002;
RA Presky D.H., Yang H., Minetti L.J., Chua A.O., Nabavi N., Wu C.-Y.,
RA Gately M.K., Gubler U.;
RT "A functional interleukin 12 receptor complex is composed of two beta-type
RT cytokine receptor subunits.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:14002-14007(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 692-699, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP FUNCTION IN STAT3/STAT4 ACTIVATION, AND MUTAGENESIS OF TYR-677; TYR-693;
RP TYR-727; TYR-737; TYR-748; TYR-757; TYR-778; TYR-804; TYR-811 AND TYR-866.
RX PubMed=12370372; DOI=10.4049/jimmunol.169.8.4388;
RA Nishikomori R., Usui T., Wu C.-Y., Morinobu A., O'Shea J.J., Strober W.;
RT "Activated STAT4 has an essential role in Th1 differentiation and
RT proliferation that is independent of its role in the maintenance of IL-12R
RT beta 2 chain expression and signaling.";
RL J. Immunol. 169:4388-4398(2002).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=9120387; DOI=10.1084/jem.185.5.817;
RA Szabo S.J., Dighe A.S., Gubler U., Murphy K.M.;
RT "Regulation of the interleukin (IL)-12R beta 2 subunit expression in
RT developing T helper 1 (Th1) and Th2 cells.";
RL J. Exp. Med. 185:817-824(1997).
RN [6]
RP IL12 UNRESPONSIVENESS IN CR MUTANT MICE.
RX PubMed=11489994; DOI=10.4049/jimmunol.167.4.2106;
RA Poltorak A., Merlin T., Nielsen P.J., Sandra O., Smirnova I., Schupp I.,
RA Boehm T., Galanos C., Freudenberg M.A.;
RT "A point mutation in the IL-12R beta 2 gene underlies the IL-12
RT unresponsiveness of Lps-defective C57BL/10ScCr mice.";
RL J. Immunol. 167:2106-2111(2001).
CC -!- FUNCTION: Receptor for interleukin-12. This subunit is the signaling
CC component coupling to the JAK2/STAT4 pathway. Promotes the
CC proliferation of T-cells as well as NK cells. Induces the promotion of
CC T-cells towards the Th1 phenotype by strongly enhancing IFN-gamma
CC production. Can also activate STAT3. {ECO:0000269|PubMed:12370372}.
CC -!- SUBUNIT: Heterodimer/heterooligomer; disulfide-linked. The functional
CC high affinity IL12 receptor is composed of I12RB1 and IL12RB2. Il12RB2
CC binds JAK2 (via its N-terminal) through a membrane-proximal region of
CC the cytoplasmic domain (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P97378; Q99KY4: Gak; NbExp=7; IntAct=EBI-6253448, EBI-7652906;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in developing T-helper (TH) cells.
CC -!- DEVELOPMENTAL STAGE: Expressed at high levels in Th1 cells on day 3, 5
CC and 7 after primary activation. Very low expression in Th2 cells on day
CC 3 and not detectable on day 5 nor day 7 after activation.
CC {ECO:0000269|PubMed:9120387}.
CC -!- INDUCTION: Following T-cell activation, expression inhibited by IL4 and
CC induced by IFN gamma.
CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC folding and thereby efficient intracellular transport and cell-surface
CC receptor binding.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation.
CC -!- PTM: On IL12 stimulation, phosphorylated on C-terminal tyrosine
CC residues. Phosphorylation of any one of Tyr-757, Tyr-804 or Tyr-811 can
CC activate STAT4, IFN-gamma production, and T-cell proliferation. Tyr-811
CC is the dominant site of cell proliferation.
CC -!- MISCELLANEOUS: Lps-defective mice C57BL/10ScCr (Cr) mice carry a
CC mutation in the IL12RB2 gene leading to the production of a truncated
CC IL12 receptor beta 2 chain resulting in malfunction of the IL12-
CC mediated IFN-gamma response.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 2
CC subfamily. {ECO:0000305}.
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DR EMBL; U64199; AAB36676.1; -; mRNA.
DR EMBL; BC137745; AAI37746.1; -; mRNA.
DR CCDS; CCDS20220.1; -.
DR RefSeq; NP_001298070.1; NM_001311141.1.
DR RefSeq; NP_032380.1; NM_008354.3.
DR RefSeq; XP_006505680.1; XM_006505617.3.
DR AlphaFoldDB; P97378; -.
DR SMR; P97378; -.
DR BioGRID; 200612; 1.
DR ComplexPortal; CPX-388; Interleukin-12-receptor complex.
DR IntAct; P97378; 3.
DR MINT; P97378; -.
DR STRING; 10090.ENSMUSP00000010605; -.
DR GlyGen; P97378; 14 sites.
DR PhosphoSitePlus; P97378; -.
DR EPD; P97378; -.
DR PaxDb; P97378; -.
DR PRIDE; P97378; -.
DR Antibodypedia; 19617; 371 antibodies from 35 providers.
DR DNASU; 16162; -.
DR Ensembl; ENSMUST00000018485; ENSMUSP00000010605; ENSMUSG00000018341.
DR GeneID; 16162; -.
DR KEGG; mmu:16162; -.
DR UCSC; uc009cfo.1; mouse.
DR CTD; 3595; -.
DR MGI; MGI:1270861; Il12rb2.
DR VEuPathDB; HostDB:ENSMUSG00000018341; -.
DR eggNOG; ENOG502QRRE; Eukaryota.
DR GeneTree; ENSGT00940000159829; -.
DR HOGENOM; CLU_016653_0_0_1; -.
DR InParanoid; P97378; -.
DR OMA; KWAKECT; -.
DR OrthoDB; 144839at2759; -.
DR PhylomeDB; P97378; -.
DR TreeFam; TF338122; -.
DR Reactome; R-MMU-8984722; Interleukin-35 Signalling.
DR Reactome; R-MMU-9020591; Interleukin-12 signaling.
DR BioGRID-ORCS; 16162; 6 hits in 73 CRISPR screens.
DR ChiTaRS; Il12rb2; mouse.
DR PRO; PR:P97378; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P97378; protein.
DR Bgee; ENSMUSG00000018341; Expressed in animal zygote and 39 other tissues.
DR ExpressionAtlas; P97378; baseline and differential.
DR Genevisible; P97378; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042022; C:interleukin-12 receptor complex; IC:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; IC:ComplexPortal.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IMP:MGI.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISO:MGI.
DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; ISO:MGI.
DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; ISO:MGI.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISO:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:ComplexPortal.
DR GO; GO:0034097; P:response to cytokine; IMP:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IGI:MGI.
DR CDD; cd00063; FN3; 3.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR003529; Hematopoietin_rcpt_Gp130_CS.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR010457; IgC2-like_lig-bd.
DR Pfam; PF00041; fn3; 3.
DR Pfam; PF06328; Lep_receptor_Ig; 1.
DR SMART; SM00060; FN3; 4.
DR SUPFAM; SSF49265; SSF49265; 4.
DR PROSITE; PS50853; FN3; 4.
DR PROSITE; PS01353; HEMATOPO_REC_L_F2; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..874
FT /note="Interleukin-12 receptor subunit beta-2"
FT /id="PRO_0000010921"
FT TOPO_DOM 24..637
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 638..658
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 659..874
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 139..237
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 242..335
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 336..430
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 438..530
FT /note="Fibronectin type-III 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 536..635
FT /note="Fibronectin type-III 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT MOTIF 321..325
FT /note="WSXWS motif"
FT MOTIF 677..685
FT /note="Box 1 motif"
FT MOD_RES 757
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES 804
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305"
FT MOD_RES 811
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q99665, ECO:0000305"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 391
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 677
FT /note="Y->F: No loss of IL12-induced STAT4 activation nor
FT T-cell proliferation. No effect on IFN-gamma production."
FT /evidence="ECO:0000269|PubMed:12370372"
FT MUTAGEN 693
FT /note="Y->F: No loss of IL12-induced STAT4 activation nor
FT T-cell proliferation. No effect on IFN-gamma production."
FT /evidence="ECO:0000269|PubMed:12370372"
FT MUTAGEN 727
FT /note="Y->F: No loss of IL12-induced STAT4 activation nor
FT T-cell proliferation. No effect on IFN-gamma production."
FT /evidence="ECO:0000269|PubMed:12370372"
FT MUTAGEN 737
FT /note="Y->F: No loss of IL12-induced STAT4 activation nor
FT T-cell proliferation. No effect on IFN-gamma production."
FT /evidence="ECO:0000269|PubMed:12370372"
FT MUTAGEN 748
FT /note="Y->F: No loss of IL12-induced STAT4 activation nor
FT T-cell proliferation. No effect on IFN-gamma production."
FT /evidence="ECO:0000269|PubMed:12370372"
FT MUTAGEN 757
FT /note="Y->F: No loss of IL12-induced STAT4 activation nor
FT T-cell proliferation. No effect on IFN-gamma production."
FT /evidence="ECO:0000269|PubMed:12370372"
FT MUTAGEN 778
FT /note="Y->F: No loss of IL12-induced STAT4 activation nor
FT T-cell proliferation. No effect on IFN-gamma production."
FT /evidence="ECO:0000269|PubMed:12370372"
FT MUTAGEN 804
FT /note="Y->F: No loss of IL12-induced STAT4 activation nor
FT T-cell proliferation. No effect on IFN-gamma production."
FT /evidence="ECO:0000269|PubMed:12370372"
FT MUTAGEN 811
FT /note="Y->F: No loss of IL12-induced STAT4 activation.
FT Greatly reduced IL12-induced T-cell proliferation and IFN-
FT gamma production."
FT /evidence="ECO:0000269|PubMed:12370372"
FT MUTAGEN 866
FT /note="Y->F: No loss of IL12-induced STAT4 activation nor
FT T-cell proliferation. No effect on IFN-gamma production."
FT /evidence="ECO:0000269|PubMed:12370372"
SQ SEQUENCE 874 AA; 98197 MW; 582E4D21BF1FBD67 CRC64;
MAQTVRECSL ALLFLFMWLL IKANIDVCKL GTVTVQPAPV IPLGSAANIS CSLNPKQGCS
HYPSSNELIL LKFVNDVLVE NLHGKKVHDH TGHSSTFQVT NLSLGMTLFV CKLNCSNSQK
KPPVPVCGVE ISVGVAPEPP QNISCVQEGE NGTVACSWNS GKVTYLKTNY TLQLSGPNNL
TCQKQCFSDN RQNCNRLDLG INLSPDLAES RFIVRVTAIN DLGNSSSLPH TFTFLDIVIP
LPPWDIRINF LNASGSRGTL QWEDEGQVVL NQLRYQPLNS TSWNMVNATN AKGKYDLRDL
RPFTEYEFQI SSKLHLSGGS WSNWSESLRT RTPEEEPVGI LDIWYMKQDI DYDRQQISLF
WKSLNPSEAR GKILHYQVTL QEVTKKTTLQ NTTRHTSWTR VIPRTGAWTA SVSAANSKGA
SAPTHINIVD LCGTGLLAPH QVSAKSENMD NILVTWQPPK KADSAVREYI VEWRALQPGS
ITKFPPHWLR IPPDNMSALI SENIKPYICY EIRVHALSES QGGCSSIRGD SKHKAPVSGP
HITAITEKKE RLFISWTHIP FPEQRGCILH YRIYWKERDS TAQPELCEIQ YRRSQNSHPI
SSLQPRVTYV LWMTAVTAAG ESPQGNEREF CPQGKANWKA FVISSICIAI ITVGTFSIRY
FRQKAFTLLS TLKPQWYSRT IPDPANSTWV KKYPILEEKI QLPTDNLLMA WPTPEEPEPL
IIHEVLYHMI PVVRQPYYFK RGQGFQGYST SKQDAMYIAN PQATGTLTAE TRQLVNLYKV
LESRDPDSKL ANLTSPLTVT PVNYLPSHEG YLPSNIEDLS PHEADPTDSF DLEHQHISLS
IFASSSLRPL IFGGERLTLD RLKMGYDSLM SNEA
