ID   IL12A_BUBCA             Reviewed;         221 AA.
AC   Q2PE77;
DT   31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   07-FEB-2006, sequence version 1.
DT   03-AUG-2022, entry version 56.
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   Bubalus carabanensis (Swamp type water buffalo) (Bubalus bubalis
OS   carabanensis).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bubalus.
OX   NCBI_TaxID=346063;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=16870267; DOI=10.1016/j.vetimm.2006.06.005;
RA   Mingala C.N., Odbileg R., Konnai S., Ohashi K., Onuma M.;
RT   "Comparative assessment of Th1 and Th2 cytokines of swamp type buffalo and
RT   other bubaline breeds by molecular cloning, sequencing and phylogenetics.";
RL   Vet. Immunol. Immunopathol. 113:348-356(2006).
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; AB246272; BAE75849.1; -; mRNA.
DR   AlphaFoldDB; Q2PE77; -.
DR   SMR; Q2PE77; -.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
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; IEA:InterPro.
DR   GO; GO:0006955; P:immune response; IEA:InterPro.
DR   GO; GO:0009893; P:positive regulation of metabolic process; IEA:UniProt.
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; Secreted; Signal.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000250"
FT   CHAIN           26..221
FT                   /note="Interleukin-12 subunit alpha"
FT                   /id="PRO_0000254898"
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;  24950 MW;  B9D4170E48B76321 CRC64;
     MCPLRSLLLI STLVLLHHLP HLSLGRSLPT TTASPGRSCL DYSQNLLRAV SNTLQKARQT
     LEFYSCTSEE IDHEDITKDK TSTVEACLPL ELATNESCLA SRETSFITNG RCLASGKTSF
     MTTLCLRSIY EDLKMYHVEF QAMNAKLLMD PKRQVFLDQN MLAAIAELMQ ALNFDSETVP
     QKPSLEELDF YKTKVKLCIL LHAFRIRAVT IDRMMSYLSS S