IL12A_BOVIN
ID IL12A_BOVIN Reviewed; 221 AA.
AC P54349; A9QWR3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 140.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Holstein; TISSUE=Lymphoid tissue;
RX PubMed=7727547; DOI=10.1016/0925-4439(95)00042-3;
RA Zarlenga D.S., Canals A., Aschenbrenner R.A., Gasbarre L.C.;
RT "Enzymatic amplification and molecular cloning of cDNA encoding the small
RT and large subunits of bovine interleukin 12.";
RL Biochim. Biophys. Acta 1270:215-217(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Belted Galloway; TISSUE=Peripheral blood;
RG U.S. Veterinary Immune Reagent Network;
RA Hudgens T., Tompkins D., Baldwin C.L.;
RT "U.S. veterinary immune reagent network: expressed bovine gene sequences.";
RL Submitted (NOV-2007) 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; U14416; AAA85810.1; -; mRNA.
DR EMBL; EU276075; ABX72073.1; -; mRNA.
DR RefSeq; NP_776780.1; NM_174355.2.
DR AlphaFoldDB; P54349; -.
DR SMR; P54349; -.
DR STRING; 9913.ENSBTAP00000020153; -.
DR PaxDb; P54349; -.
DR Ensembl; ENSBTAT00000070542; ENSBTAP00000058318; ENSBTAG00000015150.
DR GeneID; 281856; -.
DR KEGG; bta:281856; -.
DR CTD; 3592; -.
DR VEuPathDB; HostDB:ENSBTAG00000015150; -.
DR VGNC; VGNC:30110; IL12A.
DR eggNOG; ENOG502S8JN; Eukaryota.
DR GeneTree; ENSGT00390000016906; -.
DR HOGENOM; CLU_108538_0_0_1; -.
DR InParanoid; P54349; -.
DR OrthoDB; 1409826at2759; -.
DR TreeFam; TF330814; -.
DR Proteomes; UP000009136; Chromosome 1.
DR Bgee; ENSBTAG00000015150; Expressed in spermatocyte and 56 other tissues.
DR ExpressionAtlas; P54349; baseline and differential.
DR GO; GO:0005615; C:extracellular space; 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:0005143; F:interleukin-12 receptor binding; IDA:UniProtKB.
DR GO; GO:0032609; P:interferon-gamma production; IDA:AgBase.
DR GO; GO:0030101; P:natural killer cell activation; ISS:UniProtKB.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:UniProtKB.
DR GO; GO:0042093; P:T-helper cell differentiation; ISS:UniProtKB.
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..25
FT /evidence="ECO:0000250"
FT CHAIN 26..221
FT /note="Interleukin-12 subunit alpha"
FT /id="PRO_0000015597"
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; 24944 MW; 0462DEE9DD33BC90 CRC64;
MCPLRSLLLI STLVLLHHLP HLSLGRSLPT TTASPGRSCL DYSQNLLRAV SNTLQKARQT
LEFYSCTSEE IDHEDITKDK TSTVEACLPL ELATNESCLA SRETSFITNG HCLASGKTSF
MTTLCLRSIY EDLKMYHVEF QAMNAKLLMD PKRQIFLDQN MLAAIAELMQ ALNFDSETVP
QKPSLKELDF YKTKVKLCIL LHAFRIRAVT IDRMMSYLSS S
