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IL12A interleukin 12A [ Homo sapiens (human) ]

Gene ID: 3592, updated on 17-Feb-2015
Official Symbol
IL12Aprovided by HGNC
Official Full Name
interleukin 12Aprovided by HGNC
Primary source
HGNC:HGNC:5969
See related
Ensembl:ENSG00000168811; HPRD:01193; MIM:161560; Vega:OTTHUMG00000158942
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
P35; CLMF; NFSK; NKSF1; IL-12A
Summary
This gene encodes a subunit of a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-independent induction of interferon (IFN)-gamma, and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity. [provided by RefSeq, Jul 2008]
Orthologs
See IL12A in MapViewer
Location:
3q25.33
Exon count:
7
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 3 NC_000003.12 (159988836..159996019)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (159706623..159713806)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene IQCJ-SCHIP1 readthrough Neighboring gene schwannomin interacting protein 1 Neighboring gene chromosome 9 open reading frame 78 pseudogene Neighboring gene uncharacterized LOC101928351 Neighboring gene IL12A antisense RNA 1 Neighboring gene long intergenic non-protein coding RNA 1100 Neighboring gene bromodomain containing 7 pseudogene 2

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.
NHGRI GWA Catalog
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
NHGRI GWA Catalog
Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1.
NHGRI GWA Catalog
Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.
NHGRI GWA Catalog
Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.
NHGRI GWA Catalog
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
NHGRI GWA Catalog
Multiple common variants for celiac disease influencing immune gene expression.
NHGRI GWA Catalog
Newly identified genetic risk variants for celiac disease related to the immune response.
NHGRI GWA Catalog
Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Levels of IL-12 in LPS-treated myeloid dendritic cells are modulated in the presence of HIV-1 gp120 PubMed
env HIV-1 gp120 inhibits early and late production of interleukin (IL)-12 by peripheral blood mononuclear cells (PBMC) PubMed
env Secretion of IL-12 is found in macrophages primed with gamma interferon (IFN-gamma) and subsequently treated with gp120 PubMed
env Apoptosis of CD4+ lymphocytes induced by HIV-1 gp120 cross-linking to CD4 is inhibited by IL-12 PubMed
env HIV-gp120 induces a significant IL-10 synthesis, which in turn inhibits IL-12 subunits mRNA accumulation and protein secretion after Staphylococcus aureus strain cowan I (SAC)-activation PubMed
Envelope surface glycoprotein gp160, precursor env IL-7 and IL-12 significantly augment proliferative responses to HIV-1 gp160 PubMed
env Chimeric HIV-1 gp140 - CD40L trimers can target and activate dendritic cells to release IL-6, IL-10 and IL-12 PubMed
Nef nef IL-12 and GM-CSF increase the magnitude of the specific immune response with higher breadth by targeting HIV-1 Nef peptides (amino acids 9-23, 11-26, 140-155, 179-193, and 181-195) PubMed
nef IL-1beta, IL-12, and IL-15 are factors involved in the upregulation of IFN-gamma expression in coculture between Nef-pulsed iDCs and NK cells PubMed
nef HIV-1 Nef upregulates IL-12 release in immature human and macaque dendritic cells PubMed
Tat tat HIV-1 Tat upregulates IL-12 expression in Jurkat T-cells, Raji B-cells, and monocyte-derived dendritic cells PubMed
tat Wild-type Tat but not Cys-22 and oxidized Tat induces CD1A-expressing monocyte-derived dendritic cells (MDDC) maturation and increases the production of cytokines TNF-alpha, IL-12, MIP-1alpha, and MIP-1beta PubMed
tat HIV-1 Tat downregulates IL-12 production by human dendritic cells by blocking extracellular calcium influx PubMed
tat HIV-1 Tat downregulates IL-12 production by human peripheral blood mononuclear cells (PBMCs) PubMed
Vpr vpr HIV-1 Vpr impairs NK cell function through cytokine dysregulation, including diminshed expression of CD107a, reduced production of IFN-gamma, differential regulation of IL-12 and TGF-beta, and activation of the Smad3 signalling pathway PubMed
vpr The C-terminal domain or the R90 residue of HIV-1 Vpr are important for Vpr-mediated IL-12 degradation via ubiquitin-dependent pathway PubMed
vpr HIV-1 Vpr downregulates the production of interleukin 12 (IL-12) in dendritic cells PubMed
vpr HIV-1 Vpr suppresses expression and secretion of IL-12 subunit p35 and IL-12 holo-protein, but not IL-12 subunit p40 PubMed
matrix gag HIV-1 Matrix upregulates levels of IL-2, IL-12 and IL-15 in natural killer cells and induces natural killer cell proliferation PubMed
reverse transcriptase gag-pol The addition of anti-IFN-gamma antibodies block the IL-12-induced downregulation of HIV-1 RT activity in HIV-1-infected macrophages PubMed

Go to the HIV-1, Human Interaction Database

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  • African trypanosomiasis, conserved biosystem (from KEGG)
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  • Allograft rejection, conserved biosystem (from KEGG)
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  • Amoebiasis, organism-specific biosystem (from KEGG)
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  • Amoebiasis, conserved biosystem (from KEGG)
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  • Chagas disease (American trypanosomiasis), organism-specific biosystem (from KEGG)
    Chagas disease (American trypanosomiasis), organism-specific biosystemTrypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease. The parasite life cycle involves hematophagous reduviid bugs as vectors. Once parasites enter the host body, they ...
  • Chagas disease (American trypanosomiasis), conserved biosystem (from KEGG)
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  • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
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  • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
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  • Herpes simplex infection, organism-specific biosystem (from KEGG)
    Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Herpes simplex infection, conserved biosystem (from KEGG)
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  • IL12-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    IL12-mediated signaling events, organism-specific biosystem
    IL12-mediated signaling events
  • IL27-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    IL27-mediated signaling events, organism-specific biosystem
    IL27-mediated signaling events
  • Inflammatory bowel disease (IBD), organism-specific biosystem (from KEGG)
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  • Inflammatory bowel disease (IBD), conserved biosystem (from KEGG)
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  • Influenza A, organism-specific biosystem (from KEGG)
    Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Influenza A, conserved biosystem (from KEGG)
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  • Jak-STAT signaling pathway, organism-specific biosystem (from KEGG)
    Jak-STAT signaling pathway, organism-specific biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
  • Jak-STAT signaling pathway, conserved biosystem (from KEGG)
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  • Legionellosis, organism-specific biosystem (from KEGG)
    Legionellosis, organism-specific biosystemLegionellosis is a potentially fatal infectious disease caused by the bacterium Legionella pneumophila and other legionella species. Two distinct clinical and epidemiological syndromes are associated...
  • Legionellosis, conserved biosystem (from KEGG)
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  • Leishmaniasis, organism-specific biosystem (from KEGG)
    Leishmaniasis, organism-specific biosystemLeishmania is an intracellular protozoan parasite of macrophages that causes visceral, mucosal, and cutaneous diseases. The parasite is transmitted to humans by sandflies, where they survive and prol...
  • Leishmaniasis, conserved biosystem (from KEGG)
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  • Malaria, organism-specific biosystem (from KEGG)
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  • Measles, organism-specific biosystem (from KEGG)
    Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
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  • Pertussis, organism-specific biosystem (from KEGG)
    Pertussis, organism-specific biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
  • Pertussis, conserved biosystem (from KEGG)
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  • RIG-I-like receptor signaling pathway, organism-specific biosystem (from KEGG)
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  • RIG-I-like receptor signaling pathway, conserved biosystem (from KEGG)
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  • Regulation of toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
    Regulation of toll-like receptor signaling pathway, organism-specific biosystem
    Regulation of toll-like receptor signaling pathway
  • Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
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  • Toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
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  • Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
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  • Toxoplasmosis, organism-specific biosystem (from KEGG)
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  • Toxoplasmosis, conserved biosystem (from KEGG)
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  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
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  • Type I diabetes mellitus, organism-specific biosystem (from KEGG)
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  • Type I diabetes mellitus, conserved biosystem (from KEGG)
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Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
contributes_to cytokine activity IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to cytokine activity TAS
Traceable Author Statement
more info
PubMed 
contributes_to growth factor activity IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to growth factor activity NAS
Non-traceable Author Statement
more info
PubMed 
interleukin-12 beta subunit binding IPI
Inferred from Physical Interaction
more info
PubMed 
interleukin-12 receptor binding NAS
Non-traceable Author Statement
more info
PubMed 
interleukin-27 binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein heterodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
cell cycle arrest IDA
Inferred from Direct Assay
more info
PubMed 
cell migration IDA
Inferred from Direct Assay
more info
PubMed 
defense response to Gram-positive bacterium IEP
Inferred from Expression Pattern
more info
PubMed 
defense response to protozoan IEA
Inferred from Electronic Annotation
more info
 
extrinsic apoptotic signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
immune response TAS
Traceable Author Statement
more info
PubMed 
negative regulation of interleukin-17 production IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of smooth muscle cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of NK T cell activation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of T cell differentiation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of T cell mediated cytotoxicity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of T cell proliferation IBA
Inferred from Biological aspect of Ancestor
more info
 
positive regulation of cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interferon-gamma production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of lymphocyte proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of mononuclear cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of natural killer cell activation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of natural killer cell mediated cytotoxicity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of smooth muscle cell apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of tyrosine phosphorylation of Stat4 protein IDA
Inferred from Direct Assay
more info
PubMed 
response to UV-B IDA
Inferred from Direct Assay
more info
PubMed 
response to lipopolysaccharide IDA
Inferred from Direct Assay
more info
PubMed 
response to virus IEP
Inferred from Expression Pattern
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IEA
Inferred from Electronic Annotation
more info
 
extracellular space IDA
Inferred from Direct Assay
more info
PubMed 
interleukin-12 complex IDA
Inferred from Direct Assay
more info
PubMed 
interleukin-12 complex NAS
Non-traceable Author Statement
more info
PubMed 
Preferred Names
interleukin-12 subunit alpha
Names
interleukin-12 subunit alpha
CLMF p35
IL-12, subunit p35
IL35 subunit
NF cell stimulatory factor chain 1
NK cell stimulatory factor chain 1
cytotoxic lymphocyte maturation factor 1, p35
cytotoxic lymphocyte maturation factor 35 kDa subunit
interleukin 12, p35
interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35)
interleukin-12 alpha chain

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_033022.1 RefSeqGene

    Range
    5001..12184
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000882.3NP_000873.2  interleukin-12 subunit alpha precursor

    See proteins identical to NP_000873.2

    Status: REVIEWED

    Source sequence(s)
    AC010370, AW472810, BC104982, M65291
    Consensus CDS
    CCDS3187.1
    UniProtKB/TrEMBL
    O60595
    UniProtKB/Swiss-Prot
    P29459
    Related
    ENSP00000303231, OTTHUMP00000213703, ENST00000305579, OTTHUMT00000352602
    Conserved Domains (1) summary
    pfam03039
    Location:35253
    IL12; Interleukin-12 alpha subunit

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38 Primary Assembly

    Range
    159988836..159996019
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005247435.1XP_005247492.1  

    UniProtKB/TrEMBL
    E9PGR3
    Related
    ENSP00000419046, OTTHUMP00000213705, ENST00000466512, OTTHUMT00000352607
    Conserved Domains (1) summary
    pfam03039
    Location:35239
    IL12; Interleukin-12 alpha subunit

Alternate CHM1_1.1

Genomic

  1. NC_018914.2 Alternate CHM1_1.1

    Range
    159669641..159676836
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000135.1 Alternate HuRef

    Range
    157102994..157110193
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)