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Protein

Interleukin-12 subunit beta

Gene

IL12B

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

Functioni

Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.1 Publication
Associates with IL23A to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis.1 Publication

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • cytokine receptor activity Source: InterPro
  • identical protein binding Source: IntAct
  • interleukin-12 alpha subunit binding Source: AgBase
  • interleukin-12 receptor binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: Ensembl

GO - Biological processi

  • cell cycle arrest Source: BHF-UCL
  • cell migration Source: UniProtKB
  • cell proliferation Source: Ensembl
  • cellular response to interferon-gamma Source: Ensembl
  • cellular response to lipopolysaccharide Source: Ensembl
  • cytokine-mediated signaling pathway Source: Reactome
  • defense response to Gram-negative bacterium Source: BHF-UCL
  • defense response to protozoan Source: Ensembl
  • defense response to virus Source: Ensembl
  • interferon-gamma biosynthetic process Source: UniProtKB
  • interleukin-12-mediated signaling pathway Source: Reactome
  • interleukin-23-mediated signaling pathway Source: Reactome
  • natural killer cell activation Source: UniProtKB
  • natural killer cell activation involved in immune response Source: Ensembl
  • negative regulation of growth of symbiont in host Source: Ensembl
  • negative regulation of inflammatory response to antigenic stimulus Source: Ensembl
  • negative regulation of interleukin-10 production Source: BHF-UCL
  • negative regulation of interleukin-17 production Source: BHF-UCL
  • negative regulation of smooth muscle cell proliferation Source: BHF-UCL
  • positive regulation of activated T cell proliferation Source: UniProtKB
  • positive regulation of activation of Janus kinase activity Source: BHF-UCL
  • positive regulation of cell adhesion Source: UniProtKB
  • positive regulation of defense response to virus by host Source: BHF-UCL
  • positive regulation of granulocyte macrophage colony-stimulating factor production Source: BHF-UCL
  • positive regulation of inflammatory response Source: BHF-UCL
  • positive regulation of interferon-gamma biosynthetic process Source: UniProtKB
  • positive regulation of interferon-gamma production Source: UniProtKB
  • positive regulation of interleukin-10 production Source: BHF-UCL
  • positive regulation of interleukin-12 production Source: BHF-UCL
  • positive regulation of interleukin-17 production Source: BHF-UCL
  • positive regulation of lymphocyte proliferation Source: UniProtKB
  • positive regulation of memory T cell differentiation Source: BHF-UCL
  • positive regulation of mononuclear cell proliferation Source: AgBase
  • positive regulation of natural killer cell activation Source: UniProtKB
  • positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target Source: UniProtKB
  • positive regulation of natural killer cell proliferation Source: BHF-UCL
  • positive regulation of NIK/NF-kappaB signaling Source: BHF-UCL
  • positive regulation of NK T cell activation Source: BHF-UCL
  • positive regulation of NK T cell proliferation Source: BHF-UCL
  • positive regulation of osteoclast differentiation Source: BHF-UCL
  • positive regulation of smooth muscle cell apoptotic process Source: BHF-UCL
  • positive regulation of T cell mediated cytotoxicity Source: BHF-UCL
  • positive regulation of T cell proliferation Source: BHF-UCL
  • positive regulation of T-helper 17 cell lineage commitment Source: BHF-UCL
  • positive regulation of T-helper 17 type immune response Source: BHF-UCL
  • positive regulation of T-helper 1 type immune response Source: BHF-UCL
  • positive regulation of tissue remodeling Source: BHF-UCL
  • positive regulation of tumor necrosis factor production Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of STAT protein Source: BHF-UCL
  • regulation of cytokine biosynthetic process Source: UniProtKB
  • regulation of tyrosine phosphorylation of STAT protein Source: BHF-UCL
  • response to UV-B Source: UniProtKB
  • sensory perception of pain Source: Ensembl
  • sexual reproduction Source: BHF-UCL
  • T-helper 1 cell cytokine production Source: Ensembl
  • T-helper 1 type immune response Source: UniProtKB
  • T-helper cell differentiation Source: UniProtKB

Keywordsi

Molecular functionCytokine

Enzyme and pathway databases

ReactomeiR-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-9020591 Interleukin-12 signaling
R-HSA-9020933 Interleukin-23 signaling
SIGNORiP29460

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-12 subunit beta
Short name:
IL-12B
Alternative name(s):
Cytotoxic lymphocyte maturation factor 40 kDa subunit
Short name:
CLMF p40
IL-12 subunit p40
NK cell stimulatory factor chain 2
Short name:
NKSF2
Gene namesi
Name:IL12B
Synonyms:NKSF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113302.4
HGNCiHGNC:5970 IL12B
MIMi161561 gene
neXtProtiNX_P29460

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 29 (IMD29)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD29 is characterized by undetectable IL12B secretion from leukocytes. Affected individuals generally present with BCG disease after vaccination in childhood, and at least half also have Salmonella infection. Disease phenotype is relatively mild, and patients have a good prognosis.
See also OMIM:614890
Psoriasis 11 (PSORS11)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis.
See also OMIM:612599

Organism-specific databases

DisGeNETi3593
MalaCardsiIL12B
MIMi612599 phenotype
614890 phenotype
OpenTargetsiENSG00000113302
Orphaneti319558 Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency
3287 Takayasu arteritis
PharmGKBiPA29785

Chemistry databases

ChEMBLiCHEMBL3580484
DrugBankiDB02763 5-Mercapto-2-Nitro-Benzoic Acid
DB05459 Briakinumab
DB05848 humanized SMART Anti-IL-12 Antibody
DB05679 Ustekinumab

Polymorphism and mutation databases

BioMutaiIL12B
DMDMi266320

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 221 PublicationAdd BLAST22
ChainiPRO_000001093023 – 328Interleukin-12 subunit betaAdd BLAST306

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi50 ↔ 90PROSITE-ProRule annotation1 Publication
Disulfide bondi131 ↔ 142PROSITE-ProRule annotation1 Publication
Glycosylationi135N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi170 ↔ 193PROSITE-ProRule annotation1 Publication
Disulfide bondi199Interchain (with C-96 in IL12A)PROSITE-ProRule annotation1 Publication
Glycosylationi222N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi300 ↔ 327PROSITE-ProRule annotation1 Publication
GlycosylationiCAR_000187319C-linked (Man) tryptophan1 Publication1

Post-translational modificationi

Known to be C-mannosylated in the recombinant protein; it is not yet known for sure if the wild-type protein is also modified.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP29460
PeptideAtlasiP29460
PRIDEiP29460

PTM databases

GlyConnecti296
iPTMnetiP29460
PhosphoSitePlusiP29460
UniCarbKBiP29460

Miscellaneous databases

PMAP-CutDBiP29460

Expressioni

Gene expression databases

BgeeiENSG00000113302
CleanExiHS_IL12B
GenevisibleiP29460 HS

Organism-specific databases

HPAiHPA040970

Interactioni

Subunit structurei

Heterodimer with IL12A; disulfide-linked. The heterodimer is known as interleukin IL-12. Heterodimer with IL23A; disulfide-linked. The heterodimer is known as interleukin IL-23. Also secreted as a monomer.4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cytokine activity Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • interleukin-12 alpha subunit binding Source: AgBase
  • interleukin-12 receptor binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: Ensembl

Protein-protein interaction databases

BioGridi109807, 3 interactors
CORUMiP29460
DIPiDIP-3774N
ELMiP29460
IntActiP29460, 4 interactors
STRINGi9606.ENSP00000231228

Structurei

Secondary structure

1328
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi24 – 27Combined sources4
Beta strandi30 – 36Combined sources7
Beta strandi44 – 49Combined sources6
Beta strandi51 – 53Combined sources3
Beta strandi59 – 62Combined sources4
Beta strandi70 – 79Combined sources10
Helixi82 – 84Combined sources3
Beta strandi86 – 92Combined sources7
Beta strandi95 – 108Combined sources14
Beta strandi116 – 118Combined sources3
Beta strandi122 – 126Combined sources5
Beta strandi130 – 147Combined sources18
Beta strandi150 – 160Combined sources11
Beta strandi162 – 164Combined sources3
Beta strandi166 – 170Combined sources5
Beta strandi174 – 181Combined sources8
Beta strandi184 – 197Combined sources14
Beta strandi200 – 202Combined sources3
Beta strandi208 – 216Combined sources9
Beta strandi219 – 227Combined sources9
Helixi229 – 232Combined sources4
Beta strandi239 – 245Combined sources7
Beta strandi249 – 257Combined sources9
Beta strandi260 – 262Combined sources3
Turni266 – 268Combined sources3
Beta strandi271 – 278Combined sources8
Beta strandi287 – 299Combined sources13
Beta strandi302 – 304Combined sources3
Beta strandi305 – 315Combined sources11
Beta strandi323 – 326Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1F42X-ray2.50A23-328[»]
1F45X-ray2.80A23-328[»]
3D85X-ray1.90D23-328[»]
3D87X-ray2.90B/D23-328[»]
3DUHX-ray2.30A/B23-328[»]
3HMXX-ray3.00A23-328[»]
3QWRX-ray3.25A23-328[»]
4GRWX-ray2.55B/D1-328[»]
5MJ3X-ray1.74A23-328[»]
5MJ4X-ray3.40A23-328[»]
5MXAX-ray2.50A1-328[»]
5MZVX-ray2.80A1-328[»]
5NJDX-ray3.90A/C/E/G/I/K1-328[»]
ProteinModelPortaliP29460
SMRiP29460
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP29460

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 106Ig-like C2-typeAdd BLAST84
Domaini237 – 328Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST92

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal

Phylogenomic databases

eggNOGiENOG410IF5K Eukaryota
ENOG410YWXR LUCA
GeneTreeiENSGT00390000012630
HOGENOMiHOG000113027
HOVERGENiHBG052094
InParanoidiP29460
KOiK05425
OMAiWSTPHSY
OrthoDBiEOG091G0EKV
PhylomeDBiP29460
TreeFamiTF334829

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 3 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR003530 Hematopoietin_rcpt_L_F3_CS
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003598 Ig_sub2
IPR015528 IL-12_beta
IPR019482 IL-12_beta_cen-dom
PANTHERiPTHR44982 PTHR44982, 1 hit
PfamiView protein in Pfam
PF10420 IL12p40_C, 1 hit
PIRSFiPIRSF038007 IL_12_beta, 1 hit
PRINTSiPR01928 INTRLEUKN12B
SMARTiView protein in SMART
SM00408 IGc2, 1 hit
SUPFAMiSSF48726 SSF48726, 1 hit
SSF49265 SSF49265, 2 hits
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
PS01354 HEMATOPO_REC_L_F3, 1 hit
PS50835 IG_LIKE, 1 hit

Sequencei

Sequence statusi: Complete.

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

P29460-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MCHQQLVISW FSLVFLASPL VAIWELKKDV YVVELDWYPD APGEMVVLTC
60 70 80 90 100
DTPEEDGITW TLDQSSEVLG SGKTLTIQVK EFGDAGQYTC HKGGEVLSHS
110 120 130 140 150
LLLLHKKEDG IWSTDILKDQ KEPKNKTFLR CEAKNYSGRF TCWWLTTIST
160 170 180 190 200
DLTFSVKSSR GSSDPQGVTC GAATLSAERV RGDNKEYEYS VECQEDSACP
210 220 230 240 250
AAEESLPIEV MVDAVHKLKY ENYTSSFFIR DIIKPDPPKN LQLKPLKNSR
260 270 280 290 300
QVEVSWEYPD TWSTPHSYFS LTFCVQVQGK SKREKKDRVF TDKTSATVIC
310 320
RKNASISVRA QDRYYSSSWS EWASVPCS
Length:328
Mass (Da):37,169
Last modified:April 1, 1993 - v1
Checksum:i118FA801B8F5BB2F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti239K → N in AAA59938 (PubMed:1673147).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02000133V → I1 PublicationCorresponds to variant dbSNP:rs3213096EnsemblClinVar.1
Natural variantiVAR_049170298V → F1 PublicationCorresponds to variant dbSNP:rs3213119EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M65272 mRNA Translation: AAA35695.1
M65290 mRNA Translation: AAA59938.1
AY008847 Genomic DNA Translation: AAG32620.1
AF180563 mRNA Translation: AAD56386.1
AF512686 Genomic DNA Translation: AAM34792.1
BC067498 mRNA Translation: AAH67498.1
BC067499 mRNA Translation: AAH67499.1
BC067500 mRNA Translation: AAH67500.1
BC067501 mRNA Translation: AAH67501.1
BC067502 mRNA Translation: AAH67502.1
BC074723 mRNA Translation: AAH74723.1
CCDSiCCDS4346.1
PIRiA38957
RefSeqiNP_002178.2, NM_002187.2
UniGeneiHs.674

Genome annotation databases

EnsembliENST00000231228; ENSP00000231228; ENSG00000113302
GeneIDi3593
KEGGihsa:3593
UCSCiuc003lxr.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIL12B_HUMAN
AccessioniPrimary (citable) accession number: P29460
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: May 23, 2018
This is version 205 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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