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IL10_CHICK
ID   IL10_CHICK              Reviewed;         175 AA.
AC   Q6A2H4; Q6A2H5;
DT   24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT   24-JUL-2007, sequence version 2.
DT   03-AUG-2022, entry version 132.
DE   RecName: Full=Interleukin-10;
DE            Short=IL-10;
DE   Flags: Precursor;
GN   Name=IL10 {ECO:0000312|EMBL:CAF21727.1};
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC   Phasianinae; Gallus.
OX   NCBI_TaxID=9031;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:CAF21727.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC   TISSUE=Cecum {ECO:0000269|PubMed:15294985};
RX   PubMed=15294985; DOI=10.4049/jimmunol.173.4.2675;
RA   Rothwell L., Young J.R., Zoorob R., Whittaker C.A., Hesketh P., Archer A.,
RA   Smith A.L., Kaiser P.;
RT   "Cloning and characterization of chicken IL-10 and its role in the immune
RT   response to Eimeria maxima.";
RL   J. Immunol. 173:2675-2682(2004).
RN   [2] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RX   PubMed=15932414; DOI=10.1111/j.1365-2052.2005.01264.x;
RA   Yilmaz A., Shen S., Adelson D.L., Xavier S., Zhu J.;
RT   "Annotation of the chicken IL10 gene cluster and effects of
RT   lipopolysaccharide stimulation on IL10 gene expression.";
RL   Anim. Genet. 36:263-265(2005).
RN   [3] {ECO:0000305}
RP   INDUCTION.
RX   PubMed=16996141; DOI=10.1016/j.vetimm.2006.07.007;
RA   Hong Y.H., Lillehoj H.S., Lee S.H., Dalloul R.A., Lillehoj E.P.;
RT   "Analysis of chicken cytokine and chemokine gene expression following
RT   Eimeria acervulina and Eimeria tenella infections.";
RL   Vet. Immunol. Immunopathol. 114:209-223(2006).
RN   [4] {ECO:0000305}
RP   INDUCTION.
RX   PubMed=17045659; DOI=10.1016/j.vetimm.2006.08.006;
RA   Hong Y.H., Lillehoj H.S., Lillehoj E.P., Lee S.H.;
RT   "Changes in immune-related gene expression and intestinal lymphocyte
RT   subpopulations following Eimeria maxima infection of chickens.";
RL   Vet. Immunol. Immunopathol. 114:259-272(2006).
RN   [5] {ECO:0000305}
RP   DEVELOPMENTAL STAGE.
RX   PubMed=17575181; DOI=10.1093/ps/86.7.1351;
RA   Abdul-Careem M.F., Hunter D.B., Lambourne M.D., Barta J., Sharif S.;
RT   "Ontogeny of cytokine gene expression in the chicken spleen.";
RL   Poult. Sci. 86:1351-1355(2007).
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       {ECO:0000250|UniProtKB:P18893, ECO:0000250|UniProtKB:P22301}.
CC   -!- SUBUNIT: Homodimer. Interacts with IL10RA and IL10RB.
CC       {ECO:0000250|UniProtKB:P22301}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P22301}.
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in bursa of Fabricius and
CC       cecal tonsils with low levels in thymus, liver and lung.
CC       {ECO:0000269|PubMed:15294985}.
CC   -!- DEVELOPMENTAL STAGE: Expression is detected as early as embryonic day
CC       12. Higher expression in spleen of post-hatch chickens than embryos.
CC       Gradual increase in expression in the spleen which peaks by day 7 post-
CC       hatch. {ECO:0000269|PubMed:17575181}.
CC   -!- INDUCTION: By lipopolysaccharide (LPS) in white blood cells, liver and
CC       spleen 3 hours after treatment. Decreases to basal levels 8 hours after
CC       treatment. By primary infection with E.acervulina and E.tenella.
CC       {ECO:0000269|PubMed:15932414, ECO:0000269|PubMed:16996141,
CC       ECO:0000269|PubMed:17045659}.
CC   -!- MISCELLANEOUS: Chickens susceptible to E.maxima infection show higher
CC       constitutive and post-infection levels in spleen and higher post-
CC       infection levels in small intestine than infection-resistant animals.
CC       {ECO:0000269|PubMed:15294985}.
CC   -!- SIMILARITY: Belongs to the IL-10 family. {ECO:0000255}.
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DR   EMBL; AJ621614; CAF21727.1; -; Genomic_DNA.
DR   EMBL; AJ621254; CAF18432.1; -; mRNA.
DR   EMBL; AY647438; -; NOT_ANNOTATED_CDS; mRNA.
DR   RefSeq; NP_001004414.2; NM_001004414.2.
DR   AlphaFoldDB; Q6A2H4; -.
DR   SMR; Q6A2H4; -.
DR   STRING; 9031.ENSGALP00000001310; -.
DR   PaxDb; Q6A2H4; -.
DR   PRIDE; Q6A2H4; -.
DR   Ensembl; ENSGALT00000001312; ENSGALP00000001310; ENSGALG00000000892.
DR   GeneID; 428264; -.
DR   KEGG; gga:428264; -.
DR   CTD; 3586; -.
DR   VEuPathDB; HostDB:geneid_428264; -.
DR   eggNOG; ENOG502S22U; Eukaryota.
DR   GeneTree; ENSGT00950000183124; -.
DR   HOGENOM; CLU_127747_0_0_1; -.
DR   InParanoid; Q6A2H4; -.
DR   OMA; MIQFYLV; -.
DR   OrthoDB; 1389566at2759; -.
DR   PhylomeDB; Q6A2H4; -.
DR   PRO; PR:Q6A2H4; -.
DR   Proteomes; UP000000539; Chromosome 26.
DR   Bgee; ENSGALG00000000892; Expressed in granulocyte and 1 other tissue.
DR   ExpressionAtlas; Q6A2H4; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0046983; F:protein dimerization activity; IEA:Ensembl.
DR   GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IEA:Ensembl.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR   GO; GO:0002439; P:chronic inflammatory response to antigenic stimulus; IEA:Ensembl.
DR   GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl.
DR   GO; GO:0042832; P:defense response to protozoan; IDA:UniProtKB.
DR   GO; GO:0010507; P:negative regulation of autophagy; IEA:Ensembl.
DR   GO; GO:0030889; P:negative regulation of B cell proliferation; IEA:Ensembl.
DR   GO; GO:0002875; P:negative regulation of chronic inflammatory response to antigenic stimulus; IEA:Ensembl.
DR   GO; GO:0060302; P:negative regulation of cytokine activity; IEA:Ensembl.
DR   GO; GO:0002719; P:negative regulation of cytokine production involved in immune response; IEA:Ensembl.
DR   GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IEA:Ensembl.
DR   GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; IEA:Ensembl.
DR   GO; GO:1903208; P:negative regulation of hydrogen peroxide-induced neuron death; IEA:Ensembl.
DR   GO; GO:0032689; P:negative regulation of interferon-gamma production; IDA:UniProtKB.
DR   GO; GO:0032695; P:negative regulation of interleukin-12 production; IEA:Ensembl.
DR   GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
DR   GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; IEA:Ensembl.
DR   GO; GO:0045347; P:negative regulation of MHC class II biosynthetic process; IEA:Ensembl.
DR   GO; GO:0030886; P:negative regulation of myeloid dendritic cell activation; IEA:Ensembl.
DR   GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0002826; P:negative regulation of T-helper 1 type immune response; IC:UniProtKB.
DR   GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR   GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR   GO; GO:0002904; P:positive regulation of B cell apoptotic process; IEA:Ensembl.
DR   GO; GO:0045787; P:positive regulation of cell cycle; IEA:Ensembl.
DR   GO; GO:0001819; P:positive regulation of cytokine production; IEA:Ensembl.
DR   GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR   GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IEA:Ensembl.
DR   GO; GO:0002639; P:positive regulation of immunoglobulin production; IEA:Ensembl.
DR   GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IEA:Ensembl.
DR   GO; GO:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl.
DR   GO; GO:1900100; P:positive regulation of plasma cell differentiation; IEA:Ensembl.
DR   GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IEA:Ensembl.
DR   GO; GO:2000273; P:positive regulation of signaling receptor activity; IEA:Ensembl.
DR   GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IEA:Ensembl.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:1903034; P:regulation of response to wounding; IEA:Ensembl.
DR   GO; GO:0051384; P:response to glucocorticoid; 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   Pfam; PF00726; IL10; 1.
DR   PRINTS; PR01294; INTRLEUKIN10.
DR   SMART; SM00188; IL10; 1.
DR   SUPFAM; SSF47266; SSF47266; 1.
PE   2: Evidence at transcript level;
KW   Cytokine; Disulfide bond; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..175
FT                   /note="Interleukin-10"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000296319"
FT   DISULFID        26..123
FT                   /evidence="ECO:0000250|UniProtKB:P22301"
FT   DISULFID        77..129
FT                   /evidence="ECO:0000250|UniProtKB:P22301"
FT   CONFLICT        120
FT                   /note="M -> I (in Ref. 1; CAF21727)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   175 AA;  20514 MW;  B0966EBEAFDFB050 CRC64;
     MQTCCQALLL LLAACTLPAH CLEPTCLHFS ELLPARLREL RVKFEEIKDY FQSRDDELNI
     QLLSSELLDE FKGTFGCQSV SEMLRFYTDE VLPRAMQTST SHQQSMGDLG NMLLGLKATM
     RRCHRFFTCE KRSKAIKQIK ETFEKMDENG IYKAMGEFDI FINYIEEYLL MRRRK
 
 
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