ID   IL12B_MOUSE             Reviewed;         335 AA.
AC   P43432; Q9QUM1;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   27-MAR-2024, entry version 193.
DE   RecName: Full=Interleukin-12 subunit beta;
DE            Short=IL-12B;
DE   AltName: Full=Cytotoxic lymphocyte maturation factor 40 kDa subunit;
DE            Short=CLMF p40;
DE   AltName: Full=IL-12 subunit p40;
DE   Flags: Precursor;
GN   Name=Il12b;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Spleen;
RX   PubMed=1350290;
RA   Schoenhaut D.S., Chua A.O., Wolitzky A.G., Quinn P.M., Dwyer C.M.,
RA   Gately M.K., Gubler U.;
RT   "Cloning and expression of murine IL-12.";
RL   J. Immunol. 148:3433-3440(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8647196; DOI=10.1002/eji.1830260606;
RA   Tone Y., Thompson S.A., Babik J.M., Nolan K.F., Tone M., Raven C.,
RA   Waldmann H.;
RT   "Structure and chromosomal location of the mouse interleukin-12 p35 and p40
RT   subunit genes.";
RL   Eur. J. Immunol. 26:1222-1227(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS THR-169 AND LEU-294.
RC   STRAIN=B10.S/J, and SJL/J; TISSUE=Spleen;
RX   PubMed=10438970;
RA   Teuscher C., Butterfield R.J., Ma R.Z., Zachary J.F., Doerge R.W.,
RA   Blankenhorn E.P.;
RT   "Sequence polymorphisms in the chemokines Scya1 (TCA-3), Scya2 (monocyte
RT   chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for
RT   eae7, a locus controlling susceptibility to monophasic
RT   remitting/nonrelapsing experimental allergic encephalomyelitis.";
RL   J. Immunol. 163:2262-2266(1999).
RN   [4]
RP   FUNCTION, AND INTERACTION WITH IL23A.
RX   PubMed=11114383; DOI=10.1016/s1074-7613(00)00070-4;
RA   Oppmann B., Lesley R., Blom B., Timans J.C., Xu Y., Hunte B., Vega F.,
RA   Yu N., Wang J., Singh K.P., Zonin F., Vaisberg E., Churakova T., Liu M.-R.,
RA   Gorman D., Wagner J., Zurawski S., Liu Y.-J., Abrams J.S., Moore K.W.,
RA   Rennick D.M., de Waal-Malefyt R., Hannum C., Bazan J.F., Kastelein R.A.;
RT   "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with
RT   biological activities similar as well as distinct from IL-12.";
RL   Immunity 13:715-725(2000).
RN   [5]
RP   INTERACTION WITH NBR1, AND SUBCELLULAR LOCATION.
RX   PubMed=34374750; DOI=10.1093/ecco-jcc/jjab144;
RA   Merkley S.D., Goodfellow S.M., Guo Y., Wilton Z.E.R., Byrum J.R.,
RA   Schwalm K.C., Dinwiddie D.L., Gullapalli R.R., Deretic V.,
RA   Jimenez Hernandez A., Bradfute S.B., In J.G., Castillo E.F.;
RT   "Non-autophagy Role of Atg5 and NBR1 in Unconventional Secretion of IL-12
RT   Prevents Gut Dysbiosis and Inflammation.";
RL   J. Crohns. Colitis. 16:259-274(2022).
CC   -!- FUNCTION: Cytokine that can act as a growth factor for activated T and
CC       NK cells, enhance the lytic activity of NK/lymphokine-activated killer
CC       cells, and stimulate the production of IFN-gamma by resting PBMC.
CC       {ECO:0000250}.
CC   -!- FUNCTION: Associates with IL23A to form the IL-23 interleukin, a
CC       heterodimeric cytokine which functions in innate and adaptive immunity.
CC       IL-23 may constitute with IL-17 an acute response to infection in
CC       peripheral tissues. IL-23 binds to a heterodimeric receptor complex
CC       composed of IL12RB1 and IL23R, activates the Jak-Stat signaling
CC       cascade, stimulates memory rather than naive T-cells and promotes
CC       production of pro-inflammatory cytokines. IL-23 induces autoimmune
CC       inflammation and thus may be responsible for autoimmune inflammatory
CC       diseases and may be important for tumorigenesis.
CC       {ECO:0000269|PubMed:11114383}.
CC   -!- SUBUNIT: Heterodimer with IL12A; disulfide-linked. The heterodimer is
CC       known as interleukin IL-12. Heterodimer with IL23A; disulfide-linked.
CC       The heterodimer is known as interleukin IL-23. Also secreted as a
CC       monomer. Interacts with NBR1; this interaction promotes IL-12 secretion
CC       (PubMed:34374750). {ECO:0000250|UniProtKB:P29460}.
CC   -!- INTERACTION:
CC       P43432; Q9EQ14: Il23a; NbExp=3; IntAct=EBI-2481353, EBI-2481329;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:34374750}.
CC   -!- SIMILARITY: Belongs to the IL-12B family. {ECO:0000305}.
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DR   EMBL; M86671; AAA39296.1; -; mRNA.
DR   EMBL; S82426; AAB37383.1; -; Genomic_DNA.
DR   EMBL; S82421; AAB37383.1; JOINED; Genomic_DNA.
DR   EMBL; S82422; AAB37383.1; JOINED; Genomic_DNA.
DR   EMBL; S82424; AAB37383.1; JOINED; Genomic_DNA.
DR   EMBL; S82425; AAB37383.1; JOINED; Genomic_DNA.
DR   EMBL; AF128214; AAF22555.1; -; mRNA.
DR   EMBL; AF128215; AAF22556.1; -; mRNA.
DR   CCDS; CCDS24563.1; -.
DR   PIR; I72789; I72789.
DR   RefSeq; NP_001290173.1; NM_001303244.1.
DR   PDB; 6SFF; X-ray; 2.40 A; A=1-335.
DR   PDB; 6SMC; X-ray; 3.50 A; A/B/C/D=1-335.
DR   PDB; 6SP3; X-ray; 3.00 A; A/B=1-335.
DR   PDB; 7PUR; X-ray; 3.90 A; A/B=1-335.
DR   PDB; 7R3N; X-ray; 3.16 A; A/B/C/D=1-335.
DR   PDBsum; 6SFF; -.
DR   PDBsum; 6SMC; -.
DR   PDBsum; 6SP3; -.
DR   PDBsum; 7PUR; -.
DR   PDBsum; 7R3N; -.
DR   AlphaFoldDB; P43432; -.
DR   SMR; P43432; -.
DR   ComplexPortal; CPX-3293; Interleukin-23 complex.
DR   ComplexPortal; CPX-387; Interleukin-12 complex.
DR   ComplexPortal; CPX-388; Interleukin-12-receptor complex.
DR   ComplexPortal; CPX-389; Interleukin-23-receptor complex.
DR   DIP; DIP-6013N; -.
DR   IntAct; P43432; 1.
DR   STRING; 10090.ENSMUSP00000125867; -.
DR   ChEMBL; CHEMBL2176814; -.
DR   GlyCosmos; P43432; 4 sites, No reported glycans.
DR   GlyGen; P43432; 5 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P43432; -.
DR   PhosphoSitePlus; P43432; -.
DR   PaxDb; 10090-ENSMUSP00000125867; -.
DR   ProteomicsDB; 266966; -.
DR   Antibodypedia; 16629; 1156 antibodies from 48 providers.
DR   DNASU; 16160; -.
DR   Ensembl; ENSMUST00000102796.10; ENSMUSP00000099860.4; ENSMUSG00000004296.15.
DR   Ensembl; ENSMUST00000170513.3; ENSMUSP00000125867.2; ENSMUSG00000004296.15.
DR   GeneID; 16160; -.
DR   KEGG; mmu:16160; -.
DR   UCSC; uc007inc.2; mouse.
DR   AGR; MGI:96540; -.
DR   CTD; 3593; -.
DR   MGI; MGI:96540; Il12b.
DR   VEuPathDB; HostDB:ENSMUSG00000004296; -.
DR   eggNOG; ENOG502S0BC; Eukaryota.
DR   GeneTree; ENSGT00390000012630; -.
DR   HOGENOM; CLU_071206_1_0_1; -.
DR   InParanoid; P43432; -.
DR   OMA; XKPDPPK; -.
DR   OrthoDB; 4006511at2759; -.
DR   PhylomeDB; P43432; -.
DR   TreeFam; TF334829; -.
DR   BioGRID-ORCS; 16160; 0 hits in 62 CRISPR screens.
DR   PRO; PR:P43432; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; P43432; Protein.
DR   Bgee; ENSMUSG00000004296; Expressed in mesodermal cell in embryo and 12 other cell types or tissues.
DR   ExpressionAtlas; P43432; baseline and differential.
DR   GO; GO:0009986; C:cell surface; IDA:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR   GO; GO:0031904; C:endosome lumen; TAS:Reactome.
DR   GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR   GO; GO:0043514; C:interleukin-12 complex; IDA:MGI.
DR   GO; GO:0070743; C:interleukin-23 complex; IDA:BHF-UCL.
DR   GO; GO:0005125; F:cytokine activity; ISO:MGI.
DR   GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; IEA:Ensembl.
DR   GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR   GO; GO:0042164; F:interleukin-12 alpha subunit binding; IPI:MGI.
DR   GO; GO:0045519; F:interleukin-23 receptor binding; IEA:Ensembl.
DR   GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0016477; P:cell migration; ISO:MGI.
DR   GO; GO:0008283; P:cell population proliferation; IDA:MGI.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI.
DR   GO; GO:0071346; P:cellular response to type II interferon; IDA:MGI.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:MGI.
DR   GO; GO:0042832; P:defense response to protozoan; IDA:MGI.
DR   GO; GO:0051607; P:defense response to virus; IDA:MGI.
DR   GO; GO:0016064; P:immunoglobulin mediated immune response; IBA:GO_Central.
DR   GO; GO:0035722; P:interleukin-12-mediated signaling pathway; ISO:MGI.
DR   GO; GO:0030101; P:natural killer cell activation; ISS:UniProtKB.
DR   GO; GO:0002323; P:natural killer cell activation involved in immune response; ISO:MGI.
DR   GO; GO:1903588; P:negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISO:MGI.
DR   GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; IMP:MGI.
DR   GO; GO:0032693; P:negative regulation of interleukin-10 production; ISO:MGI.
DR   GO; GO:0032700; P:negative regulation of interleukin-17 production; ISO:MGI.
DR   GO; GO:0050709; P:negative regulation of protein secretion; ISO:MGI.
DR   GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR   GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; ISO:MGI.
DR   GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB.
DR   GO; GO:0045785; P:positive regulation of cell adhesion; ISO:MGI.
DR   GO; GO:0002230; P:positive regulation of defense response to virus by host; IDA:BHF-UCL.
DR   GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:MGI.
DR   GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI.
DR   GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:MGI.
DR   GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:MGI.
DR   GO; GO:0050671; P:positive regulation of lymphocyte proliferation; ISO:MGI.
DR   GO; GO:0032946; P:positive regulation of mononuclear cell proliferation; ISO:MGI.
DR   GO; GO:0032816; P:positive regulation of natural killer cell activation; ISO:MGI.
DR   GO; GO:0002860; P:positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target; ISO:MGI.
DR   GO; GO:0032819; P:positive regulation of natural killer cell proliferation; ISO:MGI.
DR   GO; GO:0051135; P:positive regulation of NK T cell activation; ISO:MGI.
DR   GO; GO:0051142; P:positive regulation of NK T cell proliferation; ISO:MGI.
DR   GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:MGI.
DR   GO; GO:0034393; P:positive regulation of smooth muscle cell apoptotic process; ISO:MGI.
DR   GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IDA:BHF-UCL.
DR   GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:MGI.
DR   GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; IDA:BHF-UCL.
DR   GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR   GO; GO:0032729; P:positive regulation of type II interferon production; IDA:MGI.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR   GO; GO:0042509; P:regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR   GO; GO:0010033; P:response to organic substance; IDA:MGI.
DR   GO; GO:0010224; P:response to UV-B; ISO:MGI.
DR   GO; GO:0042098; P:T cell proliferation; IDA:MGI.
DR   GO; GO:0042093; P:T-helper cell differentiation; ISS:UniProtKB.
DR   CDD; cd00063; FN3; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 3.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR036116; FN3_sf.
DR   InterPro; IPR003530; Hematopoietin_rcpt_L_F3_CS.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003598; Ig_sub2.
DR   InterPro; IPR015528; IL-12_beta.
DR   InterPro; IPR019482; IL-12_beta_cen-dom.
DR   PANTHER; PTHR48397:SF1; INTERLEUKIN-12 SUBUNIT BETA; 1.
DR   PANTHER; PTHR48397; INTERLEUKIN-12 SUBUNIT BETA-RELATED; 1.
DR   Pfam; PF10420; IL12p40_C; 1.
DR   PIRSF; PIRSF038007; IL_12_beta; 1.
DR   PRINTS; PR01928; INTRLEUKN12B.
DR   SMART; SM00408; IGc2; 1.
DR   SUPFAM; SSF49265; Fibronectin type III; 2.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   PROSITE; PS01354; HEMATOPO_REC_L_F3; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   Genevisible; P43432; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Cytokine; Disulfide bond; Glycoprotein;
KW   Immunoglobulin domain; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000250"
FT   CHAIN           23..335
FT                   /note="Interleukin-12 subunit beta"
FT                   /id="PRO_0000010933"
FT   DOMAIN          23..106
FT                   /note="Ig-like C2-type"
FT   DOMAIN          233..324
FT                   /note="Fibronectin type-III"
FT   CARBOHYD        47
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        122
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        132
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        220
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        50..90
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        197
FT                   /note="Interchain (with C-92 in IL12A and C-74 in IL23A)"
FT                   /evidence="ECO:0000250|UniProtKB:P29460"
FT   VARIANT         169
FT                   /note="M -> T (in strain: B10.S/J and SJL/J)"
FT                   /evidence="ECO:0000269|PubMed:10438970"
FT   VARIANT         294
FT                   /note="F -> L (in strain: B10.S/J and SJL/J)"
FT                   /evidence="ECO:0000269|PubMed:10438970"
FT   STRAND          24..27
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          30..36
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          44..49
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          51..53
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          56..62
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          65..67
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          70..79
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   HELIX           82..84
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          86..92
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          95..108
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          116..118
FT                   /evidence="ECO:0007829|PDB:6SP3"
FT   STRAND          127..144
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          147..156
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          159..162
FT                   /evidence="ECO:0007829|PDB:6SMC"
FT   STRAND          165..167
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          171..179
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          182..195
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          198..200
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          206..214
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          217..225
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   HELIX           227..229
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          237..244
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          248..254
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   TURN            263..265
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          268..274
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          294..296
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          298..303
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          306..319
FT                   /evidence="ECO:0007829|PDB:6SFF"
FT   STRAND          327..330
FT                   /evidence="ECO:0007829|PDB:6SFF"
SQ   SEQUENCE   335 AA;  38235 MW;  19E4FA5EF0CFC82A CRC64;
     MCPQKLTISW FAIVLLVSPL MAMWELEKDV YVVEVDWTPD APGETVNLTC DTPEEDDITW
     TSDQRHGVIG SGKTLTITVK EFLDAGQYTC HKGGETLSHS HLLLHKKENG IWSTEILKNF
     KNKTFLKCEA PNYSGRFTCS WLVQRNMDLK FNIKSSSSSP DSRAVTCGMA SLSAEKVTLD
     QRDYEKYSVS CQEDVTCPTA EETLPIELAL EARQQNKYEN YSTSFFIRDI IKPDPPKNLQ
     MKPLKNSQVE VSWEYPDSWS TPHSYFSLKF FVRIQRKKEK MKETEEGCNQ KGAFLVEKTS
     TEVQCKGGNV CVQAQDRYYN SSCSKWACVP CRVRS
//