IL12B_MOUSE
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 03-AUG-2022, entry version 184.
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).
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.
CC -!- INTERACTION:
CC P43432; Q9EQ14: Il23a; NbExp=3; IntAct=EBI-2481353, EBI-2481329;
CC -!- SUBCELLULAR LOCATION: Secreted.
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 PDBsum; 6SFF; -.
DR PDBsum; 6SMC; -.
DR PDBsum; 6SP3; -.
DR PDBsum; 7PUR; -.
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 GlyGen; P43432; 4 sites.
DR iPTMnet; P43432; -.
DR PhosphoSitePlus; P43432; -.
DR PaxDb; P43432; -.
DR PRIDE; P43432; -.
DR ProteomicsDB; 266966; -.
DR Antibodypedia; 16629; 979 antibodies from 48 providers.
DR DNASU; 16160; -.
DR Ensembl; ENSMUST00000102796; ENSMUSP00000099860; ENSMUSG00000004296.
DR Ensembl; ENSMUST00000170513; ENSMUSP00000125867; ENSMUSG00000004296.
DR GeneID; 16160; -.
DR KEGG; mmu:16160; -.
DR UCSC; uc007inc.2; mouse.
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; SWEKPCT; -.
DR OrthoDB; 1179405at2759; -.
DR PhylomeDB; P43432; -.
DR TreeFam; TF334829; -.
DR Reactome; R-MMU-9020591; Interleukin-12 signaling.
DR Reactome; R-MMU-9020933; Interleukin-23 signaling.
DR BioGRID-ORCS; 16160; 0 hits in 59 CRISPR screens.
DR PRO; PR:P43432; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P43432; protein.
DR Bgee; ENSMUSG00000004296; Expressed in lumbar subsegment of spinal cord and 11 other tissues.
DR ExpressionAtlas; P43432; baseline and differential.
DR Genevisible; P43432; MM.
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:ComplexPortal.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0043514; C:interleukin-12 complex; IDA:MGI.
DR GO; GO:0042022; C:interleukin-12 receptor complex; IC:ComplexPortal.
DR GO; GO:0070743; C:interleukin-23 complex; IDA:BHF-UCL.
DR GO; GO:0072536; C:interleukin-23 receptor complex; IC:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; ISO:MGI.
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; ISO:MGI.
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:0071346; P:cellular response to interferon-gamma; IDA:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; 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:0006955; P:immune response; IC:ComplexPortal.
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:0010536; P:positive regulation of activation of Janus kinase activity; ISO:MGI.
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:0032729; P:positive regulation of interferon-gamma production; IDA: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:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; 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:ComplexPortal.
DR GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; IDA:BHF-UCL.
DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO: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:0019233; P:sensory perception of pain; 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; -; 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; PTHR23036:SF156; PTHR23036:SF156; 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; SSF48726; SSF48726; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS01354; HEMATOPO_REC_L_F3; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
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
