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Protein

Interleukin-12 receptor subunit beta-2

Gene

IL12RB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • cytokine receptor activity Source: UniProtKB

GO - Biological processi

  • cell surface receptor signaling pathway Source: ProtInc
  • interferon-gamma production Source: Ensembl
  • peptidyl-tyrosine phosphorylation Source: Ensembl
  • positive regulation of cell proliferation Source: ProtInc
  • positive regulation of interferon-gamma production Source: BHF-UCL
  • response to lipopolysaccharide Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000081985-MONOMER.
ReactomeiR-HSA-447115. Interleukin-12 signaling.
R-HSA-6788467. IL-6-type cytokine receptor ligand interactions.
SIGNORiQ99665.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:IL12RB2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:5972. IL12RB2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 622ExtracellularSequence analysisAdd BLAST599
Transmembranei623 – 643HelicalSequence analysisAdd BLAST21
Topological domaini644 – 862CytoplasmicSequence analysisAdd BLAST219

GO - Cellular componenti

  • external side of plasma membrane Source: Ensembl
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi678Y → F: No loss of STAT4 activation. No loss of SOCS3 binding. 3 Publications1
Mutagenesisi767Y → F: No loss of STAT4 activation. No loss of SOCS3 binding. 3 Publications1
Mutagenesisi800Y → F: Loss of STAT4 activation. Abolishes SOCS3 binding. 3 Publications1
Mutagenesisi801L → A: Abolishes in vitro STAT4 binding to a phosphorylated Y-800 peptide. 1 Publication1
Mutagenesisi802P → A: No effect on in vitro STAT4 binding to a phosphorylated Y-800 peptide. 1 Publication1
Mutagenesisi803S → A: No effect on in vitro STAT4 binding to a phosphorylated Y-800 peptide. 1 Publication1
Mutagenesisi804N → A: No effect on in vitro STAT4 binding to a phosphorylated Y-800 peptide. 1 Publication1

Organism-specific databases

DisGeNETi3595.
MalaCardsiIL12RB2.
OpenTargetsiENSG00000081985.
Orphaneti117. Behcet disease.
PharmGKBiPA29787.

Polymorphism and mutation databases

BioMutaiIL12RB2.
DMDMi12229836.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000001092024 – 862Interleukin-12 receptor subunit beta-2Add BLAST839

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi48N-linked (GlcNAc...)Sequence analysis1
Glycosylationi129N-linked (GlcNAc...)Sequence analysis1
Glycosylationi166N-linked (GlcNAc...)Sequence analysis1
Glycosylationi195N-linked (GlcNAc...)Sequence analysis1
Glycosylationi271N-linked (GlcNAc...)Sequence analysis1
Glycosylationi347N-linked (GlcNAc...)Sequence analysis1
Glycosylationi376N-linked (GlcNAc...)Sequence analysis1
Glycosylationi480N-linked (GlcNAc...)Sequence analysis1
Modified residuei800Phosphotyrosine1 Publication1

Post-translational modificationi

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.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ99665.
PeptideAtlasiQ99665.
PRIDEiQ99665.

PTM databases

iPTMnetiQ99665.
PhosphoSitePlusiQ99665.

Expressioni

Tissue specificityi

Isoform 2 is expressed at similar levels in both naive and activated T-cells.1 Publication

Developmental stagei

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

Inductioni

In vitro, up-regulated by IFN-alpha.1 Publication

Gene expression databases

BgeeiENSG00000081985.
CleanExiHS_IL12RB2.
ExpressionAtlasiQ99665. baseline and differential.
GenevisibleiQ99665. HS.

Organism-specific databases

HPAiHPA024168.

Interactioni

Subunit structurei

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.

Protein-protein interaction databases

BioGridi109809. 5 interactors.
DIPiDIP-6011N.
IntActiQ99665. 2 interactors.
MINTiMINT-6780861.
STRINGi9606.ENSP00000262345.

Structurei

3D structure databases

ProteinModelPortaliQ99665.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini126 – 221Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST96
Domaini226 – 319Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST94
Domaini320 – 419Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST100
Domaini423 – 520Fibronectin type-III 4PROSITE-ProRule annotationAdd BLAST98
Domaini521 – 620Fibronectin type-III 5PROSITE-ProRule annotationAdd BLAST100

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni796 – 801Required for STAT4 binding6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi305 – 309WSXWS motif5
Motifi662 – 670Box 1 motif9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi208 – 211Poly-Ser4
Compositional biasi750 – 753Poly-Pro4

Domaini

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.

Sequence similaritiesi

Contains 5 fibronectin type-III domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHXG. Eukaryota.
ENOG41116V2. LUCA.
GeneTreeiENSGT00550000074436.
HOGENOMiHOG000049086.
HOVERGENiHBG052059.
InParanoidiQ99665.
KOiK05064.
OMAiCILHYRI.
OrthoDBiEOG091G01XM.
PhylomeDBiQ99665.
TreeFamiTF338122.

Family and domain databases

CDDicd00063. FN3. 3 hits.
Gene3Di2.60.40.10. 5 hits.
InterProiIPR003961. FN3_dom.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
IPR010457. IgC2-like_lig-bd.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
PF06328. Lep_receptor_Ig. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 4 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
PROSITEiPS50853. FN3. 5 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99665-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAHTFRGCSL AFMFIITWLL IKAKIDACKR GDVTVKPSHV ILLGSTVNIT
60 70 80 90 100
CSLKPRQGCF HYSRRNKLIL YKFDRRINFH HGHSLNSQVT GLPLGTTLFV
110 120 130 140 150
CKLACINSDE IQICGAEIFV GVAPEQPQNL SCIQKGEQGT VACTWERGRD
160 170 180 190 200
THLYTEYTLQ LSGPKNLTWQ KQCKDIYCDY LDFGINLTPE SPESNFTAKV
210 220 230 240 250
TAVNSLGSSS SLPSTFTFLD IVRPLPPWDI RIKFQKASVS RCTLYWRDEG
260 270 280 290 300
LVLLNRLRYR PSNSRLWNMV NVTKAKGRHD LLDLKPFTEY EFQISSKLHL
310 320 330 340 350
YKGSWSDWSE SLRAQTPEEE PTGMLDVWYM KRHIDYSRQQ ISLFWKNLSV
360 370 380 390 400
SEARGKILHY QVTLQELTGG KAMTQNITGH TSWTTVIPRT GNWAVAVSAA
410 420 430 440 450
NSKGSSLPTR INIMNLCEAG LLAPRQVSAN SEGMDNILVT WQPPRKDPSA
460 470 480 490 500
VQEYVVEWRE LHPGGDTQVP LNWLRSRPYN VSALISENIK SYICYEIRVY
510 520 530 540 550
ALSGDQGGCS SILGNSKHKA PLSGPHINAI TEEKGSILIS WNSIPVQEQM
560 570 580 590 600
GCLLHYRIYW KERDSNSQPQ LCEIPYRVSQ NSHPINSLQP RVTYVLWMTA
610 620 630 640 650
LTAAGESSHG NEREFCLQGK ANWMAFVAPS ICIAIIMVGI FSTHYFQQKV
660 670 680 690 700
FVLLAALRPQ WCSREIPDPA NSTCAKKYPI AEEKTQLPLD RLLIDWPTPE
710 720 730 740 750
DPEPLVISEV LHQVTPVFRH PPCSNWPQRE KGIQGHQASE KDMMHSASSP
760 770 780 790 800
PPPRALQAES RQLVDLYKVL ESRGSDPKPE NPACPWTVLP AGDLPTHDGY
810 820 830 840 850
LPSNIDDLPS HEAPLADSLE ELEPQHISLS VFPSSSLHPL TFSCGDKLTL
860
DQLKMRCDSL ML
Length:862
Mass (Da):97,135
Last modified:May 1, 1997 - v1
Checksum:i67C0E0D946B8DD58
GO
Isoform 2 (identifier: Q99665-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     650-659: VFVLLAALRP → RRHSCPWTGS
     660-862: Missing.

Show »
Length:659
Mass (Da):74,607
Checksum:i66A09C2666CCC64E
GO
Isoform 3 (identifier: Q99665-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     487-572: Missing.

Note: No experimental confirmation available.
Show »
Length:776
Mass (Da):87,484
Checksum:i85F77F1E5D18E2C1
GO

Polymorphismi

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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02127813M → V.1 PublicationCorresponds to variant rs17129772dbSNPEnsembl.1
Natural variantiVAR_021279149R → Q.1 PublicationCorresponds to variant rs17129792dbSNPEnsembl.1
Natural variantiVAR_014805185I → V.Corresponds to variant rs2307146dbSNPEnsembl.1
Natural variantiVAR_019525201T → I.Corresponds to variant rs7526769dbSNPEnsembl.1
Natural variantiVAR_019526313R → G.1 Publication1
Natural variantiVAR_014806420G → R.Corresponds to variant rs2307148dbSNPEnsembl.1
Natural variantiVAR_049169420G → S.Corresponds to variant rs2307148dbSNPEnsembl.1
Natural variantiVAR_014807426Q → H.2 PublicationsCorresponds to variant rs2307145dbSNPEnsembl.1
Natural variantiVAR_014808465G → D.1 PublicationCorresponds to variant rs2307153dbSNPEnsembl.1
Natural variantiVAR_016097625A → V.Corresponds to variant rs2307154dbSNPEnsembl.1
Natural variantiVAR_019527720H → R.1 Publication1
Natural variantiVAR_021280808L → R.1 PublicationCorresponds to variant rs17838066dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044784487 – 572Missing in isoform 3. 1 PublicationAdd BLAST86
Alternative sequenceiVSP_011112650 – 659VFVLLAALRP → RRHSCPWTGS in isoform 2. 1 Publication10
Alternative sequenceiVSP_011113660 – 862Missing in isoform 2. 1 PublicationAdd BLAST203

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS58006.1. [Q99665-2]
CCDS58007.1. [Q99665-3]
CCDS638.1. [Q99665-1]
RefSeqiNP_001245143.1. NM_001258214.1. [Q99665-2]
NP_001245144.1. NM_001258215.1. [Q99665-3]
NP_001245145.1. NM_001258216.1.
NP_001306162.1. NM_001319233.1. [Q99665-2]
NP_001550.1. NM_001559.2. [Q99665-1]
XP_005270882.1. XM_005270825.2. [Q99665-1]
XP_005270884.1. XM_005270827.2. [Q99665-1]
XP_005270885.1. XM_005270828.3. [Q99665-1]
XP_006710680.1. XM_006710617.2. [Q99665-3]
XP_011539685.1. XM_011541383.2. [Q99665-1]
XP_016856692.1. XM_017001203.1. [Q99665-2]
UniGeneiHs.479347.

Genome annotation databases

EnsembliENST00000262345; ENSP00000262345; ENSG00000081985. [Q99665-1]
ENST00000371000; ENSP00000360039; ENSG00000081985. [Q99665-2]
ENST00000544434; ENSP00000442443; ENSG00000081985. [Q99665-3]
GeneIDi3595.
KEGGihsa:3595.
UCSCiuc001ddu.3. human. [Q99665-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS58006.1. [Q99665-2]
CCDS58007.1. [Q99665-3]
CCDS638.1. [Q99665-1]
RefSeqiNP_001245143.1. NM_001258214.1. [Q99665-2]
NP_001245144.1. NM_001258215.1. [Q99665-3]
NP_001245145.1. NM_001258216.1.
NP_001306162.1. NM_001319233.1. [Q99665-2]
NP_001550.1. NM_001559.2. [Q99665-1]
XP_005270882.1. XM_005270825.2. [Q99665-1]
XP_005270884.1. XM_005270827.2. [Q99665-1]
XP_005270885.1. XM_005270828.3. [Q99665-1]
XP_006710680.1. XM_006710617.2. [Q99665-3]
XP_011539685.1. XM_011541383.2. [Q99665-1]
XP_016856692.1. XM_017001203.1. [Q99665-2]
UniGeneiHs.479347.

3D structure databases

ProteinModelPortaliQ99665.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109809. 5 interactors.
DIPiDIP-6011N.
IntActiQ99665. 2 interactors.
MINTiMINT-6780861.
STRINGi9606.ENSP00000262345.

PTM databases

iPTMnetiQ99665.
PhosphoSitePlusiQ99665.

Polymorphism and mutation databases

BioMutaiIL12RB2.
DMDMi12229836.

Proteomic databases

PaxDbiQ99665.
PeptideAtlasiQ99665.
PRIDEiQ99665.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262345; ENSP00000262345; ENSG00000081985. [Q99665-1]
ENST00000371000; ENSP00000360039; ENSG00000081985. [Q99665-2]
ENST00000544434; ENSP00000442443; ENSG00000081985. [Q99665-3]
GeneIDi3595.
KEGGihsa:3595.
UCSCiuc001ddu.3. human. [Q99665-1]

Organism-specific databases

CTDi3595.
DisGeNETi3595.
GeneCardsiIL12RB2.
HGNCiHGNC:5972. IL12RB2.
HPAiHPA024168.
MalaCardsiIL12RB2.
MIMi601642. gene.
neXtProtiNX_Q99665.
OpenTargetsiENSG00000081985.
Orphaneti117. Behcet disease.
PharmGKBiPA29787.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHXG. Eukaryota.
ENOG41116V2. LUCA.
GeneTreeiENSGT00550000074436.
HOGENOMiHOG000049086.
HOVERGENiHBG052059.
InParanoidiQ99665.
KOiK05064.
OMAiCILHYRI.
OrthoDBiEOG091G01XM.
PhylomeDBiQ99665.
TreeFamiTF338122.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000081985-MONOMER.
ReactomeiR-HSA-447115. Interleukin-12 signaling.
R-HSA-6788467. IL-6-type cytokine receptor ligand interactions.
SIGNORiQ99665.

Miscellaneous databases

ChiTaRSiIL12RB2. human.
GeneWikiiInterleukin_12_receptor,_beta_2_subunit.
GenomeRNAii3595.
PROiQ99665.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000081985.
CleanExiHS_IL12RB2.
ExpressionAtlasiQ99665. baseline and differential.
GenevisibleiQ99665. HS.

Family and domain databases

CDDicd00063. FN3. 3 hits.
Gene3Di2.60.40.10. 5 hits.
InterProiIPR003961. FN3_dom.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
IPR010457. IgC2-like_lig-bd.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
PF06328. Lep_receptor_Ig. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 4 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
PROSITEiPS50853. FN3. 5 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiI12R2_HUMAN
AccessioniPrimary (citable) accession number: Q99665
Secondary accession number(s): B1AN98
, B7ZKL9, F5H7L6, Q2M3V3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 1997
Last modified: November 30, 2016
This is version 164 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.