P29459 · IL12A_HUMAN
- ProteinInterleukin-12 subunit alpha
- GeneIL12A
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids219 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Heterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine (PubMed:8605935, PubMed:8943050).
IL-12 is primarily produced by professional antigen-presenting cells (APCs) such as B-cells and dendritic cells (DCs) as well as macrophages and granulocytes and regulates T-cell and natural killer-cell responses, induces the production of interferon-gamma (IFN-gamma), favors the differentiation of T-helper 1 (Th1) cells and is an important link between innate resistance and adaptive immunity (PubMed:1673147, PubMed:1674604, PubMed:8605935).
Mechanistically, exerts its biological effects through a receptor composed of IL12R1 and IL12R2 subunits (PubMed:8943050).
Binding to the receptor results in the rapid tyrosine phosphorylation of a number of cellular substrates including the JAK family kinases TYK2 and JAK2 (PubMed:7528775).
In turn, recruited STAT4 gets phosphorylated and translocates to the nucleus where it regulates cytokine/growth factor responsive genes (PubMed:7638186).
As part of IL-35, plays essential roles in maintaining the immune homeostasis of the liver microenvironment and functions also as an immune-suppressive cytokine (By similarity).
Mediates biological events through unconventional receptors composed of IL12RB2 and gp130/IL6ST heterodimers or homodimers (PubMed:22306691).
Signaling requires the transcription factors STAT1 and STAT4, which form a unique heterodimer that binds to distinct DNA sites (PubMed:22306691).
IL-12 is primarily produced by professional antigen-presenting cells (APCs) such as B-cells and dendritic cells (DCs) as well as macrophages and granulocytes and regulates T-cell and natural killer-cell responses, induces the production of interferon-gamma (IFN-gamma), favors the differentiation of T-helper 1 (Th1) cells and is an important link between innate resistance and adaptive immunity (PubMed:1673147, PubMed:1674604, PubMed:8605935).
Mechanistically, exerts its biological effects through a receptor composed of IL12R1 and IL12R2 subunits (PubMed:8943050).
Binding to the receptor results in the rapid tyrosine phosphorylation of a number of cellular substrates including the JAK family kinases TYK2 and JAK2 (PubMed:7528775).
In turn, recruited STAT4 gets phosphorylated and translocates to the nucleus where it regulates cytokine/growth factor responsive genes (PubMed:7638186).
As part of IL-35, plays essential roles in maintaining the immune homeostasis of the liver microenvironment and functions also as an immune-suppressive cytokine (By similarity).
Mediates biological events through unconventional receptors composed of IL12RB2 and gp130/IL6ST heterodimers or homodimers (PubMed:22306691).
Signaling requires the transcription factors STAT1 and STAT4, which form a unique heterodimer that binds to distinct DNA sites (PubMed:22306691).
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameInterleukin-12 subunit alpha
- Short namesIL-12A
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP29459
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 173 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-22 | |||||
Sequence: MCPARSLLLVATLVLLDHLSLA | ||||||
Chain | PRO_0000015604 | 23-219 | Interleukin-12 subunit alpha | |||
Sequence: RNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS | ||||||
Disulfide bond | 37↔110 | |||||
Sequence: CLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSC | ||||||
Disulfide bond | 64↔196 | |||||
Sequence: CTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFYKTKIKLC | ||||||
Disulfide bond | 85↔123 | |||||
Sequence: CLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALC | ||||||
Glycosylation | 93 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 96 | Interchain (with C-199 in IL12B) | ||||
Sequence: C | ||||||
Glycosylation | 107 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
(Microbial infection) By pathogenic organisms, including Gram- positive and Gram-negative bacteria, parasites, viruses, and fungi.Down-regulated in response to enterovirus 71 (EV71) infection.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Heterodimer with IL12B; disulfide-linked (PubMed:10899108, PubMed:1674604).
This heterodimer is known as interleukin IL-12 (PubMed:1674604).
Heterodimer with EBI3/IL27B; not disulfide-linked (PubMed:9342359).
This heterodimer is known as interleukin IL-35 (PubMed:9342359).
Interacts with NBR1; this interaction promotes IL-12 secretion (By similarity).
This heterodimer is known as interleukin IL-12 (PubMed:1674604).
Heterodimer with EBI3/IL27B; not disulfide-linked (PubMed:9342359).
This heterodimer is known as interleukin IL-35 (PubMed:9342359).
Interacts with NBR1; this interaction promotes IL-12 secretion (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P29459 | IL12B P29460 | 2 | EBI-1029636, EBI-1029614 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length219
- Mass (Da)24,874
- Last updated2002-01-23 v2
- Checksum7C658AB7716112B2
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 213 | in Ref. 2; AAA35694 | ||||
Sequence: M → T |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M65291 EMBL· GenBank· DDBJ | AAA59937.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
M65271 EMBL· GenBank· DDBJ | AAA35694.1 EMBL· GenBank· DDBJ | mRNA | ||
AF404773 EMBL· GenBank· DDBJ | AAK84425.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AC010370 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |