IL12A_SHEEP
ID IL12A_SHEEP Reviewed; 221 AA.
AC Q9TU27; Q9MYU0;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 96.
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; Synonyms=IL12P35;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBUNIT.
RC TISSUE=Kidney;
RX PubMed=11023671; DOI=10.1006/cyto.2000.0755;
RA Swinburne S.J., Russ G.R., Krishnan R.;
RT "Ovine interleukin 12 has biological activity on ovine and human activated
RT peripheral blood mononuclear cells.";
RL Cytokine 12:1546-1552(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 72-132.
RX PubMed=11086544; DOI=10.1046/j.1365-2052.2000.00643.x;
RA Schmidt P., Kuehn C., Kang'a S., Hanotte O., Vanselow J., Anton I.,
RA Langner C., Schwerin M.;
RT "Interleukin-12 p35 encoding gene of cattle and sheep harbours a
RT polymorphic T stretch in intron 4.";
RL Anim. Genet. 31:283-285(2000).
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 (PubMed:11023671).
CC This heterodimer is known as interleukin IL-12 (PubMed:11023671).
CC Heterodimer with EBI3/IL27B; not disulfide-linked (By similarity). This
CC heterodimer is known as interleukin IL-35 (By similarity).
CC {ECO:0000250|UniProtKB:P29459, ECO:0000269|PubMed:11023671}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P29459}.
CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
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DR EMBL; AF173557; AAD51976.1; -; mRNA.
DR EMBL; AJ271035; CAB97178.1; -; Genomic_DNA.
DR RefSeq; NP_001009736.1; NM_001009736.1.
DR AlphaFoldDB; Q9TU27; -.
DR SMR; Q9TU27; -.
DR STRING; 9940.ENSOARP00000002320; -.
DR Ensembl; ENSOART00020008660; ENSOARP00020007151; ENSOARG00020005615.
DR GeneID; 443064; -.
DR KEGG; oas:443064; -.
DR CTD; 3592; -.
DR eggNOG; ENOG502S8JN; Eukaryota.
DR OrthoDB; 1409826at2759; -.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0005615; C:extracellular space; IDA:AgBase.
DR GO; GO:0043514; C:interleukin-12 complex; IDA:AgBase.
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; IPI:AgBase.
DR GO; GO:0005143; F:interleukin-12 receptor binding; IEA:InterPro.
DR GO; GO:0045513; F:interleukin-27 binding; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:AgBase.
DR GO; GO:0016477; P:cell migration; IEA:Ensembl.
DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0032609; P:interferon-gamma production; IDA:AgBase.
DR GO; GO:1903588; P:negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IEA:Ensembl.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IEA:Ensembl.
DR GO; GO:0050709; P:negative regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; IEA:Ensembl.
DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; IEA:Ensembl.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0050671; P:positive regulation of lymphocyte proliferation; IEA:Ensembl.
DR GO; GO:0032946; P:positive regulation of mononuclear cell proliferation; IMP:AgBase.
DR GO; GO:0032816; P:positive regulation of natural killer cell activation; IEA:Ensembl.
DR GO; GO:0002860; P:positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; IEA:Ensembl.
DR GO; GO:0051135; P:positive regulation of NK T cell activation; IEA:Ensembl.
DR GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0010224; P:response to UV-B; IEA:Ensembl.
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 1: Evidence at protein level;
KW Cytokine; Disulfide bond; Glycoprotein; Growth factor; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000250"
FT CHAIN 26..221
FT /note="Interleukin-12 subunit alpha"
FT /id="PRO_0000015612"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 66..198
FT /evidence="ECO:0000250"
FT DISULFID 87..125
FT /evidence="ECO:0000250"
FT DISULFID 98
FT /note="Interchain (with C-200 in IL12B)"
FT /evidence="ECO:0000250"
SQ SEQUENCE 221 AA; 24859 MW; 9E9A2300914E4167 CRC64;
MCPLRSLLLI STLVLLHHLP HLSLGRSLPT TTAGPGTSCL DYSQNLLRAV SNTLQKARQT
LEFYSCTSEE IDHEDITKDK TSTVEACLPL ELATNESCLA SRETSLITNG HCLSSGKTSF
MTTLCLRSIY KDLKMYHMEF QAMNAKLLMD PKRQVFLDQN MLAAIAELMQ ALNFDSETVP
QKPSLEELDF YKTKVKLCIL LHAFRIRAVT IDRMMSYLSS S
