IL12A_RAT
ID IL12A_RAT Reviewed; 215 AA.
AC Q9R103;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Interleukin-12 subunit alpha;
DE Short=IL-12A;
DE AltName: Full=Cytotoxic lymphocyte maturation factor 35 kDa subunit;
DE Short=CLMF p35;
DE AltName: Full=IL-12 subunit p35;
DE Flags: Precursor;
GN Name=Il12a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=DA;
RA Verma N.D., He X.Y., Hall B.M.;
RT "Cloning of the rat interleukin 12 p35 subunit.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Heterodimerizes with IL12B to form the IL-12 cytokine or with
CC EBI3/IL27B to form the IL-35 cytokine. IL-12 is primarily produced by
CC professional antigen-presenting cells (APCs) such as B-cells and
CC dendritic cells (DCs) as well as macrophages and granulocytes and
CC regulates T-cell and natural killer-cell responses, induces the
CC production of interferon-gamma (IFN-gamma), favors the differentiation
CC of T-helper 1 (Th1) cells and is an important link between innate
CC resistance and adaptive immunity. Mechanistically, exerts its
CC biological effects through a receptor composed of IL12R1 and IL12R2
CC subunits. Binding to the receptor results in the rapid tyrosine
CC phosphorylation of a number of cellular substrates including the JAK
CC family kinases TYK2 and JAK2. In turn, recruited STAT4 gets
CC phosphorylated and translocates to the nucleus where it regulates
CC cytokine/growth factor responsive genes (By similarity). As part of IL-
CC 35, plays essential roles in maintaining the immune homeostasis of the
CC liver microenvironment and functions also as an immune-suppressive
CC cytokine (By similarity). Mediates biological events through
CC unconventional receptors composed of IL12RB2 and gp130/IL6ST
CC heterodimers or homodimers. Signaling requires the transcription
CC factors STAT1 and STAT4, which form a unique heterodimer that binds to
CC distinct DNA sites (By similarity). {ECO:0000250|UniProtKB:P29459,
CC ECO:0000250|UniProtKB:P43431}.
CC -!- SUBUNIT: Heterodimer with IL12B; disulfide-linked. This heterodimer is
CC known as interleukin IL-12. Heterodimer with EBI3/IL27B; not disulfide-
CC linked. This heterodimer is known as interleukin IL-35.
CC {ECO:0000250|UniProtKB:P29459}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P29459}.
CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
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DR EMBL; AF177031; AAD51364.1; -; mRNA.
DR RefSeq; NP_445842.1; NM_053390.1.
DR AlphaFoldDB; Q9R103; -.
DR SMR; Q9R103; -.
DR STRING; 10116.ENSRNOP00000012832; -.
DR GlyGen; Q9R103; 3 sites.
DR PaxDb; Q9R103; -.
DR GeneID; 84405; -.
DR KEGG; rno:84405; -.
DR UCSC; RGD:620562; rat.
DR CTD; 3592; -.
DR RGD; 620562; Il12a.
DR eggNOG; ENOG502S8JN; Eukaryota.
DR InParanoid; Q9R103; -.
DR OrthoDB; 1409826at2759; -.
DR PhylomeDB; Q9R103; -.
DR PRO; PR:Q9R103; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0043514; C:interleukin-12 complex; ISO:RGD.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0042163; F:interleukin-12 beta subunit binding; ISO:RGD.
DR GO; GO:0005143; F:interleukin-12 receptor binding; IEA:InterPro.
DR GO; GO:0045513; F:interleukin-27 binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0016477; P:cell migration; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0098586; P:cellular response to virus; ISO:RGD.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:RGD.
DR GO; GO:0042832; P:defense response to protozoan; ISO:RGD.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:1903588; P:negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISO:RGD.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; ISO:RGD.
DR GO; GO:0050709; P:negative regulation of protein secretion; ISO:RGD.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:RGD.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; ISO:RGD.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:RGD.
DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; ISO:RGD.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISO:RGD.
DR GO; GO:0050671; P:positive regulation of lymphocyte proliferation; ISO:RGD.
DR GO; GO:0032946; P:positive regulation of mononuclear cell proliferation; ISO:RGD.
DR GO; GO:0032816; P:positive regulation of natural killer cell activation; ISO:RGD.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; ISO:RGD.
DR GO; GO:0002860; P:positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; ISO:RGD.
DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; ISO:RGD.
DR GO; GO:0051135; P:positive regulation of NK T cell activation; ISO:RGD.
DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; ISO:RGD.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISO:RGD.
DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; ISO:RGD.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; ISO:RGD.
DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; ISO:RGD.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISO:RGD.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:RGD.
DR GO; GO:1990638; P:response to granulocyte colony-stimulating factor; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0010224; P:response to UV-B; ISO:RGD.
DR GO; GO:0009615; P:response to virus; ISO:RGD.
DR GO; GO:0035711; P:T-helper 1 cell activation; ISO:RGD.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR004281; IL-12_alpha.
DR Pfam; PF03039; IL12; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
PE 2: Evidence at transcript level;
KW Cytokine; Disulfide bond; Glycoprotein; Growth factor; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000250"
FT CHAIN 23..215
FT /note="Interleukin-12 subunit alpha"
FT /id="PRO_0000015611"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 60..192
FT /evidence="ECO:0000250"
FT DISULFID 81..119
FT /evidence="ECO:0000250"
FT DISULFID 92
FT /note="Interchain"
FT /evidence="ECO:0000305"
SQ SEQUENCE 215 AA; 24246 MW; 60EDC00C70F0E005 CRC64;
MCQSRYLLFL ATLVLLNHLT SARVIPVSGP AKCLNQSQNL LKTTDDMVRT AREKLKHYSC
TAGDIDHEDI TRDKTSTLEA CLPLELHKNE SCLATKETSS IIRGSCLPPQ KTSLMMTLCL
GSIYEDLKMY QSEFQAINAA LQSHNHQQIT LDRNMLMAID ELMRSLNHSG ETLHQKAPMG
EADPYRVKMK LCILLHAFST RVMTINRVMN YLSSS
