IL10_MOUSE
ID IL10_MOUSE Reviewed; 178 AA.
AC P18893; Q0VBJ1;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Interleukin-10;
DE Short=IL-10;
DE AltName: Full=Cytokine synthesis inhibitory factor;
DE Short=CSIF;
DE Flags: Precursor;
GN Name=Il10; Synonyms=Il-10;
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].
RX PubMed=2161559; DOI=10.1126/science.2161559;
RA Moore K.W., Vieira P., Fiorentino D.F., Trounstine M.L., Khan T.A.,
RA Mosmann T.R.;
RT "Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-
RT Barr virus gene BCRFI.";
RL Science 248:1230-1234(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1350294;
RA Kim J.M., Brannan C.I., Copeland N.G., Jenkins N.A., Khan T.A., Moore K.W.;
RT "Structure of the mouse IL-10 gene and chromosomal localization of the
RT mouse and human genes.";
RL J. Immunol. 148:3618-3623(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP DISULFIDE BONDS.
RX PubMed=8364028; DOI=10.1021/bi00085a011;
RA Windsor W.T., Syto R., Tsarbopoulos A., Zhang R., Durkin J., Baldwin S.,
RA Paliwal S., Mui P.W., Pramanik B., Trotta P.P.;
RT "Disulfide bond assignments and secondary structure analysis of human and
RT murine interleukin 10.";
RL Biochemistry 32:8807-8815(1993).
RN [7]
RP FUNCTION.
RX PubMed=28473584; DOI=10.1126/science.aal3535;
RA Ip W.K.E., Hoshi N., Shouval D.S., Snapper S., Medzhitov R.;
RT "Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of
RT macrophages.";
RL Science 356:513-519(2017).
CC -!- FUNCTION: Major immune regulatory cytokine that acts on many cells of
CC the immune system where it has profound anti-inflammatory functions,
CC limiting excessive tissue disruption caused by inflammation.
CC Mechanistically, IL10 binds to its heterotetrameric receptor comprising
CC IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of
CC STAT3. In turn, STAT3 translocates to the nucleus where it drives
CC expression of anti-inflammatory mediators. Targets antigen-presenting
CC cells (APCs) such as macrophages and monocytes and inhibits their
CC release of pro-inflammatory cytokines including granulocyte-macrophage
CC colony-stimulating factor /GM-CSF, granulocyte colony-stimulating
CC factor/G-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha.
CC Interferes also with antigen presentation by reducing the expression of
CC MHC-class II and co-stimulatory molecules, thereby inhibiting their
CC ability to induce T cell activation (By similarity). In addition,
CC controls the inflammatory response of macrophages by reprogramming
CC essential metabolic pathways including mTOR signaling (By similarity)
CC (PubMed:28473584). {ECO:0000250|UniProtKB:P22301,
CC ECO:0000269|PubMed:28473584}.
CC -!- SUBUNIT: Homodimer. Interacts with IL10RA and IL10RB.
CC {ECO:0000250|UniProtKB:P22301}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P22301}.
CC -!- SIMILARITY: Belongs to the IL-10 family. {ECO:0000305}.
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DR EMBL; M37897; AAA39274.1; -; mRNA.
DR EMBL; M84340; AAA39275.1; -; Genomic_DNA.
DR EMBL; AL513351; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466520; EDL39722.1; -; Genomic_DNA.
DR EMBL; BC120612; AAI20613.1; -; mRNA.
DR EMBL; BC137844; AAI37845.1; -; mRNA.
DR CCDS; CCDS15265.1; -.
DR PIR; A34853; A34853.
DR RefSeq; NP_034678.1; NM_010548.2.
DR PDB; 4X51; X-ray; 2.05 A; A/B=27-178.
DR PDBsum; 4X51; -.
DR AlphaFoldDB; P18893; -.
DR BMRB; P18893; -.
DR SMR; P18893; -.
DR BioGRID; 200603; 1.
DR STRING; 10090.ENSMUSP00000016673; -.
DR GlyGen; P18893; 2 sites.
DR EPD; P18893; -.
DR PaxDb; P18893; -.
DR PRIDE; P18893; -.
DR Antibodypedia; 3407; 1676 antibodies from 46 providers.
DR DNASU; 16153; -.
DR Ensembl; ENSMUST00000016673; ENSMUSP00000016673; ENSMUSG00000016529.
DR GeneID; 16153; -.
DR KEGG; mmu:16153; -.
DR UCSC; uc007cmu.2; mouse.
DR CTD; 3586; -.
DR MGI; MGI:96537; Il10.
DR VEuPathDB; HostDB:ENSMUSG00000016529; -.
DR eggNOG; ENOG502S22U; Eukaryota.
DR GeneTree; ENSGT00950000183124; -.
DR HOGENOM; CLU_127747_0_0_1; -.
DR InParanoid; P18893; -.
DR OMA; MIQFYLV; -.
DR OrthoDB; 1389566at2759; -.
DR PhylomeDB; P18893; -.
DR TreeFam; TF333253; -.
DR BioGRID-ORCS; 16153; 0 hits in 75 CRISPR screens.
DR ChiTaRS; Il10; mouse.
DR PRO; PR:P18893; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; P18893; protein.
DR Bgee; ENSMUSG00000016529; Expressed in lumbar subsegment of spinal cord and 18 other tissues.
DR Genevisible; P18893; MM.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR GO; GO:0005141; F:interleukin-10 receptor binding; ISO:MGI.
DR GO; GO:0046983; F:protein dimerization activity; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IMP:MGI.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IDA:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0002439; P:chronic inflammatory response to antigenic stimulus; IMP:MGI.
DR GO; GO:0042742; P:defense response to bacterium; IDA:MGI.
DR GO; GO:0042832; P:defense response to protozoan; IDA:MGI.
DR GO; GO:0006955; P:immune response; ISO:MGI.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010507; P:negative regulation of autophagy; ISO:MGI.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0002875; P:negative regulation of chronic inflammatory response to antigenic stimulus; IMP:MGI.
DR GO; GO:0060302; P:negative regulation of cytokine activity; ISO:MGI.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISO:MGI.
DR GO; GO:0002719; P:negative regulation of cytokine production involved in immune response; ISO:MGI.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IGI:BHF-UCL.
DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; IGI:BHF-UCL.
DR GO; GO:1903208; P:negative regulation of hydrogen peroxide-induced neuron death; IGI:ARUK-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:MGI.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IMP:MGI.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IMP:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; ISO:MGI.
DR GO; GO:0045347; P:negative regulation of MHC class II biosynthetic process; ISO:MGI.
DR GO; GO:0030886; P:negative regulation of myeloid dendritic cell activation; IMP:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:1904057; P:negative regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:MGI.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IGI:BHF-UCL.
DR GO; GO:0002904; P:positive regulation of B cell apoptotic process; ISO:MGI.
DR GO; GO:0045787; P:positive regulation of cell cycle; IGI:BHF-UCL.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IGI:BHF-UCL.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISO:MGI.
DR GO; GO:0043032; P:positive regulation of macrophage activation; ISO:MGI.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IDA:MGI.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:MGI.
DR GO; GO:1900100; P:positive regulation of plasma cell differentiation; ISO:MGI.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISO:MGI.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; ISO:MGI.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:1903034; P:regulation of response to wounding; IMP:BHF-UCL.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0050807; P:regulation of synapse organization; ISO:MGI.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0034465; P:response to carbon monoxide; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; ISO:MGI.
DR GO; GO:0014854; P:response to inactivity; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0002237; P:response to molecule of bacterial origin; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR000098; IL-10.
DR InterPro; IPR020443; IL-10/19/20/22/24/26_fam.
DR InterPro; IPR020423; IL-10_CS.
DR Pfam; PF00726; IL10; 1.
DR PRINTS; PR01294; INTRLEUKIN10.
DR SMART; SM00188; IL10; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00520; INTERLEUKIN_10; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytokine; Disulfide bond; Glycoprotein; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..178
FT /note="Interleukin-10"
FT /id="PRO_0000015367"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 30..126
FT /evidence="ECO:0000269|PubMed:8364028"
FT DISULFID 80..132
FT /evidence="ECO:0000269|PubMed:8364028"
FT HELIX 39..49
FT /evidence="ECO:0007829|PDB:4X51"
FT HELIX 52..56
FT /evidence="ECO:0007829|PDB:4X51"
FT HELIX 68..75
FT /evidence="ECO:0007829|PDB:4X51"
FT HELIX 79..92
FT /evidence="ECO:0007829|PDB:4X51"
FT HELIX 94..100
FT /evidence="ECO:0007829|PDB:4X51"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:4X51"
FT HELIX 106..125
FT /evidence="ECO:0007829|PDB:4X51"
FT TURN 127..129
FT /evidence="ECO:0007829|PDB:4X51"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:4X51"
FT HELIX 137..149
FT /evidence="ECO:0007829|PDB:4X51"
FT HELIX 151..159
FT /evidence="ECO:0007829|PDB:4X51"
FT HELIX 161..174
FT /evidence="ECO:0007829|PDB:4X51"
SQ SEQUENCE 178 AA; 20641 MW; 9A283E6FFC99312B CRC64;
MPGSALLCCL LLLTGMRISR GQYSREDNNC THFPVGQSHM LLELRTAFSQ VKTFFQTKDQ
LDNILLTDSL MQDFKGYLGC QALSEMIQFY LVEVMPQAEK HGPEIKEHLN SLGEKLKTLR
MRLRRCHRFL PCENKSKAVE QVKSDFNKLQ DQGVYKAMNE FDIFINCIEA YMMIKMKS
