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Q99665 (I12R2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-12 receptor subunit beta-2

Short name=IL-12 receptor subunit beta-2
Short name=IL-12R subunit beta-2
Short name=IL-12R-beta-2
Short name=IL-12RB2
Gene names
Name:IL12RB2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length862 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 structure

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. Ref.10

Developmental stage

Maximum levels in Th1 cells between day 3 and day 8 of activation.

Induction

In vitro, up-regulated by IFN-alpha. Ref.10

Domain

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.

The box 1 motif is required for JAK interaction and/or activation.

Post-translational modification

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. Ref.7 Ref.11

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.

Sequence similarities

Belongs to the type I cytokine receptor family. Type 2 subfamily.

Contains 5 fibronectin type-III domains.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99665-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q99665-2)

The sequence of this isoform differs from the canonical sequence as follows:
     650-659: VFVLLAALRP → RRHSCPWTGS
     660-862: Missing.
Isoform 3 (identifier: Q99665-3)

The sequence of this isoform differs from the canonical sequence as follows:
     487-572: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 862839Interleukin-12 receptor subunit beta-2
PRO_0000010920

Regions

Topological domain24 – 622599Extracellular Potential
Transmembrane623 – 64321Helical; Potential
Topological domain644 – 862219Cytoplasmic Potential
Domain126 – 22196Fibronectin type-III 1
Domain226 – 31994Fibronectin type-III 2
Domain320 – 419100Fibronectin type-III 3
Domain423 – 52098Fibronectin type-III 4
Domain521 – 620100Fibronectin type-III 5
Region796 – 8016Required for STAT4 binding
Motif305 – 3095WSXWS motif
Motif662 – 6709Box 1 motif
Compositional bias208 – 2114Poly-Ser
Compositional bias750 – 7534Poly-Pro

Amino acid modifications

Modified residue8001Phosphotyrosine Ref.7
Glycosylation481N-linked (GlcNAc...) Potential
Glycosylation1291N-linked (GlcNAc...) Potential
Glycosylation1661N-linked (GlcNAc...) Potential
Glycosylation1951N-linked (GlcNAc...) Potential
Glycosylation2711N-linked (GlcNAc...) Potential
Glycosylation3471N-linked (GlcNAc...) Potential
Glycosylation3761N-linked (GlcNAc...) Potential
Glycosylation4801N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence487 – 57286Missing in isoform 3.
VSP_044784
Alternative sequence650 – 65910VFVLLAALRP → RRHSCPWTGS in isoform 2.
VSP_011112
Alternative sequence660 – 862203Missing in isoform 2.
VSP_011113
Natural variant131M → V. Ref.3
Corresponds to variant rs17129772 [ dbSNP | Ensembl ].
VAR_021278
Natural variant1491R → Q. Ref.3
Corresponds to variant rs17129792 [ dbSNP | Ensembl ].
VAR_021279
Natural variant1851I → V.
Corresponds to variant rs2307146 [ dbSNP | Ensembl ].
VAR_014805
Natural variant2011T → I.
Corresponds to variant rs7526769 [ dbSNP | Ensembl ].
VAR_019525
Natural variant3131R → G. Ref.12
VAR_019526
Natural variant4201G → R.
Corresponds to variant rs2307148 [ dbSNP | Ensembl ].
VAR_014806
Natural variant4201G → S.
Corresponds to variant rs2307148 [ dbSNP | Ensembl ].
VAR_049169
Natural variant4261Q → H. Ref.3 Ref.6
Corresponds to variant rs2307145 [ dbSNP | Ensembl ].
VAR_014807
Natural variant4651G → D. Ref.3
Corresponds to variant rs2307153 [ dbSNP | Ensembl ].
VAR_014808
Natural variant6251A → V.
Corresponds to variant rs2307154 [ dbSNP | Ensembl ].
VAR_016097
Natural variant7201H → R. Ref.12
VAR_019527
Natural variant8081L → R. Ref.3
Corresponds to variant rs17838066 [ dbSNP | Ensembl ].
VAR_021280

Experimental info

Mutagenesis6781Y → F: No loss of STAT4 activation. No loss of SOCS3 binding. Ref.8 Ref.9 Ref.11
Mutagenesis7671Y → F: No loss of STAT4 activation. No loss of SOCS3 binding. Ref.8 Ref.9 Ref.11
Mutagenesis8001Y → F: Loss of STAT4 activation. Abolishes SOCS3 binding. Ref.8 Ref.9 Ref.11
Mutagenesis8011L → A: Abolishes in vitro STAT4 binding to a phosphorylated Y-800 peptide. Ref.7
Mutagenesis8021P → A: No effect on in vitro STAT4 binding to a phosphorylated Y-800 peptide. Ref.7
Mutagenesis8031S → A: No effect on in vitro STAT4 binding to a phosphorylated Y-800 peptide. Ref.7
Mutagenesis8041N → A: No effect on in vitro STAT4 binding to a phosphorylated Y-800 peptide. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1997. Version 1.
Checksum: 67C0E0D946B8DD58

FASTA86297,135
        10         20         30         40         50         60 
MAHTFRGCSL AFMFIITWLL IKAKIDACKR GDVTVKPSHV ILLGSTVNIT CSLKPRQGCF 

        70         80         90        100        110        120 
HYSRRNKLIL YKFDRRINFH HGHSLNSQVT GLPLGTTLFV CKLACINSDE IQICGAEIFV 

       130        140        150        160        170        180 
GVAPEQPQNL SCIQKGEQGT VACTWERGRD THLYTEYTLQ LSGPKNLTWQ KQCKDIYCDY 

       190        200        210        220        230        240 
LDFGINLTPE SPESNFTAKV TAVNSLGSSS SLPSTFTFLD IVRPLPPWDI RIKFQKASVS 

       250        260        270        280        290        300 
RCTLYWRDEG LVLLNRLRYR PSNSRLWNMV NVTKAKGRHD LLDLKPFTEY EFQISSKLHL 

       310        320        330        340        350        360 
YKGSWSDWSE SLRAQTPEEE PTGMLDVWYM KRHIDYSRQQ ISLFWKNLSV SEARGKILHY 

       370        380        390        400        410        420 
QVTLQELTGG KAMTQNITGH TSWTTVIPRT GNWAVAVSAA NSKGSSLPTR INIMNLCEAG 

       430        440        450        460        470        480 
LLAPRQVSAN SEGMDNILVT WQPPRKDPSA VQEYVVEWRE LHPGGDTQVP LNWLRSRPYN 

       490        500        510        520        530        540 
VSALISENIK SYICYEIRVY ALSGDQGGCS SILGNSKHKA PLSGPHINAI TEEKGSILIS 

       550        560        570        580        590        600 
WNSIPVQEQM GCLLHYRIYW KERDSNSQPQ LCEIPYRVSQ NSHPINSLQP RVTYVLWMTA 

       610        620        630        640        650        660 
LTAAGESSHG NEREFCLQGK ANWMAFVAPS ICIAIIMVGI FSTHYFQQKV FVLLAALRPQ 

       670        680        690        700        710        720 
WCSREIPDPA NSTCAKKYPI AEEKTQLPLD RLLIDWPTPE DPEPLVISEV LHQVTPVFRH 

       730        740        750        760        770        780 
PPCSNWPQRE KGIQGHQASE KDMMHSASSP PPPRALQAES RQLVDLYKVL ESRGSDPKPE 

       790        800        810        820        830        840 
NPACPWTVLP AGDLPTHDGY LPSNIDDLPS HEAPLADSLE ELEPQHISLS VFPSSSLHPL 

       850        860 
TFSCGDKLTL DQLKMRCDSL ML 

« Hide

Isoform 2 [UniParc].

Checksum: 66A09C2666CCC64E
Show »

FASTA65974,607
Isoform 3 [UniParc].

Checksum: 85F77F1E5D18E2C1
Show »

FASTA77687,484

References

« Hide 'large scale' references
[1]"A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits."
Presky D.H., Yang H., Minetti L.J., Chua A.O., Nabavi N., Wu C.-Y., Gately M.K., Gubler U.
Proc. Natl. Acad. Sci. U.S.A. 93:14002-14007(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Genomic organization of the human interleukin-12 receptor beta2-chain gene."
van Rietschoten J.G.I., Smits H.H., Westland R., Verweij C.L., den Hartog M.T., Wierenga E.A.
Immunogenetics 51:30-36(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: T-cell.
[3]SeattleSNPs variation discovery resource
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-13; GLN-149; HIS-426; ASP-465 AND ARG-808.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANT HIS-426.
Tissue: Brain.
[7]"Direct interaction of STAT4 with the IL-12 receptor."
Yao B.B., Niu P., Surowy C.S., Faltynek C.R.
Arch. Biochem. Biophys. 368:147-155(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STAT4, PHOSPHORYLATION AT TYR-800, MUTAGENESIS OF LEU-801; PRO-802; SER-803 AND ASN-804.
[8]"Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus."
Yamamoto K., Shibata F., Miura O., Kamiyama R., Hirosawa S., Miyasaka N.
Biochem. Biophys. Res. Commun. 257:400-404(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH JAK2, MUTAGENESIS OF TYR-678; TYR-767 AND TYR-800.
[9]"Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling."
Naeger L.K., McKinney J., Salvekar A., Hoey T.
J. Biol. Chem. 274:1875-1878(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STAT4, MUTAGENESIS OF TYR-678; TYR-767 AND TYR-800.
[10]"Selective expression of an interleukin-12 receptor component by human T helper 1 cells."
Rogge L., Barberis-Maino L., Biffi M., Passini N., Presky D.H., Gubler U., Sinigaglia F.
J. Exp. Med. 185:825-831(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
[11]"SOCS-3 inhibits IL-12-induced STAT4 activation by binding through its SH2 domain to the STAT4 docking site in the IL-12 receptor beta2 subunit."
Yamamoto K., Yamaguchi M., Miyasaka N., Miura O.
Biochem. Biophys. Res. Commun. 310:1188-1193(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, INTERACTION WITH SOCS3, MUTAGENESIS OF TYR-678; TYR-767 AND TYR-800.
[12]"Mutations of the IL-12 receptor beta2 chain gene in atopic subjects."
Matsui E., Kaneko H., Fukao T., Teramoto T., Inoue R., Watanabe M., Kasahara K., Kondo N.
Biochem. Biophys. Res. Commun. 266:551-555(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLY-313 AND ARG-720.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U64198 mRNA. Translation: AAB36675.1.
AY640177 Genomic DNA. Translation: AAT45456.1.
CH471059 Genomic DNA. Translation: EAX06499.1.
AL358512, AL389925 Genomic DNA. Translation: CAH69960.1.
AL389925, AL358512 Genomic DNA. Translation: CAH70407.1.
BC104772 mRNA. Translation: AAI04773.1.
BC104774 mRNA. Translation: AAI04775.1.
BC143249 mRNA. Translation: AAI43250.1.
CCDSCCDS58006.1. [Q99665-2]
CCDS58007.1. [Q99665-3]
CCDS638.1. [Q99665-1]
RefSeqNP_001245143.1. NM_001258214.1. [Q99665-2]
NP_001245144.1. NM_001258215.1. [Q99665-3]
NP_001245145.1. NM_001258216.1.
NP_001550.1. NM_001559.2. [Q99665-1]
XP_005270882.1. XM_005270825.1. [Q99665-1]
XP_005270884.1. XM_005270827.1. [Q99665-1]
XP_005270885.1. XM_005270828.1. [Q99665-1]
XP_006710680.1. XM_006710617.1. [Q99665-3]
UniGeneHs.479347.

3D structure databases

ProteinModelPortalQ99665.
SMRQ99665. Positions 60-605.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109809. 4 interactions.
DIPDIP-6011N.
IntActQ99665. 2 interactions.
MINTMINT-6780861.
STRING9606.ENSP00000262345.

PTM databases

PhosphoSiteQ99665.

Polymorphism databases

DMDM12229836.

Proteomic databases

PaxDbQ99665.
PRIDEQ99665.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262345; ENSP00000262345; ENSG00000081985. [Q99665-1]
ENST00000371000; ENSP00000360039; ENSG00000081985. [Q99665-2]
ENST00000541374; ENSP00000445276; ENSG00000081985. [Q99665-2]
ENST00000544434; ENSP00000442443; ENSG00000081985. [Q99665-3]
GeneID3595.
KEGGhsa:3595.
UCSCuc001ddu.3. human. [Q99665-1]
uc010oqi.2. human. [Q99665-2]

Organism-specific databases

CTD3595.
GeneCardsGC01P067773.
HGNCHGNC:5972. IL12RB2.
HPAHPA024168.
MIM601642. gene.
neXtProtNX_Q99665.
Orphanet117. Behcet disease.
PharmGKBPA29787.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG122790.
HOGENOMHOG000049086.
HOVERGENHBG052059.
InParanoidQ99665.
KOK05064.
OMATWAKKYP.
OrthoDBEOG7FXZXN.
PhylomeDBQ99665.
TreeFamTF338122.

Gene expression databases

BgeeQ99665.
CleanExHS_IL12RB2.
GenevestigatorQ99665.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
InterProIPR003961. Fibronectin_type3.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
IPR010457. IgC2-like_lig-bd.
IPR015321. IL-6_rcpt_alpha-bd.
[Graphical view]
PfamPF00041. fn3. 2 hits.
PF09240. IL6Ra-bind. 1 hit.
PF06328. Lep_receptor_Ig. 1 hit.
[Graphical view]
SMARTSM00060. FN3. 4 hits.
[Graphical view]
SUPFAMSSF49265. SSF49265. 4 hits.
PROSITEPS50853. FN3. 5 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSIL12RB2. human.
GeneWikiInterleukin_12_receptor,_beta_2_subunit.
GenomeRNAi3595.
NextBio14049.
PROQ99665.
SOURCESearch...

Entry information

Entry nameI12R2_HUMAN
AccessionPrimary (citable) accession number: Q99665
Secondary accession number(s): B1AN98 expand/collapse secondary AC list , B7ZKL9, F5H7L6, Q2M3V3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 1997
Last modified: July 9, 2014
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM