UniProt functional annotation for P22301



	UniProt functional annotation for P22301

UniProt code: P22301.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3 (PubMed:16982608). In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators (PubMed:18025162). Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro- inflammatory cytokines including granulocyte-macrophage colony- stimulating factor /GM-CSF, granulocyte colony-stimulating factor/G- CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha (PubMed:1940799, PubMed:7512027, PubMed:11564774). Interferes also with antigen presentation by reducing the expression of MHC-class II and co- stimulatory molecules, thereby inhibiting their ability to induce T cell activation (PubMed:8144879). In addition, controls the inflammatory response of macrophages by reprogramming essential metabolic pathways including mTOR signaling (By similarity). {ECO:0000250|UniProtKB:P18893, ECO:0000269|PubMed:11564774, ECO:0000269|PubMed:16982608, ECO:0000269|PubMed:18025162, ECO:0000269|PubMed:1940799, ECO:0000269|PubMed:7512027, ECO:0000269|PubMed:8144879}.

Subunit: Homodimer (PubMed:11485736, PubMed:15837194). Interacts with IL10RA and IL10RB (PubMed:16982608). {ECO:0000269|PubMed:11485736, ECO:0000269|PubMed:15837194, ECO:0000269|PubMed:16982608}.

Subcellular location: Secreted.

Tissue specificity: Produced by a variety of cell lines, including T- cells, macrophages, mast cells and other cell types. {ECO:0000269|PubMed:1940799, ECO:0000269|PubMed:7512027}.

Polymorphism: A polymorphism in IL10 promoter region is associated with resistance to graft-versus-host disease (GVHDS) [MIM:614395]. GVHDS is a major complication of allogeneic bone marrow transplantation, in which mature donor T-cells that contaminate the allogeneic bone marrow recognize the tissues of the recipient as foreign, causing a severe inflammatory disease. {ECO:0000269|PubMed:14657427}.

Similarity: Belongs to the IL-10 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3 (PubMed:16982608). In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators (PubMed:18025162). Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro- inflammatory cytokines including granulocyte-macrophage colony- stimulating factor /GM-CSF, granulocyte colony-stimulating factor/G- CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha (PubMed:1940799, PubMed:7512027, PubMed:11564774). Interferes also with antigen presentation by reducing the expression of MHC-class II and co- stimulatory molecules, thereby inhibiting their ability to induce T cell activation (PubMed:8144879). In addition, controls the inflammatory response of macrophages by reprogramming essential metabolic pathways including mTOR signaling (By similarity). {ECO:0000250\|UniProtKB:P18893, ECO:0000269\|PubMed:11564774, ECO:0000269\|PubMed:16982608, ECO:0000269\|PubMed:18025162, ECO:0000269\|PubMed:1940799, ECO:0000269\|PubMed:7512027, ECO:0000269\|PubMed:8144879}.


Subunit:		Homodimer (PubMed:11485736, PubMed:15837194). Interacts with IL10RA and IL10RB (PubMed:16982608). {ECO:0000269\|PubMed:11485736, ECO:0000269\|PubMed:15837194, ECO:0000269\|PubMed:16982608}.
Subcellular location:		Secreted.
Tissue specificity:		Produced by a variety of cell lines, including T- cells, macrophages, mast cells and other cell types. {ECO:0000269\|PubMed:1940799, ECO:0000269\|PubMed:7512027}.
Polymorphism:		A polymorphism in IL10 promoter region is associated with resistance to graft-versus-host disease (GVHDS) [MIM:614395]. GVHDS is a major complication of allogeneic bone marrow transplantation, in which mature donor T-cells that contaminate the allogeneic bone marrow recognize the tissues of the recipient as foreign, causing a severe inflammatory disease. {ECO:0000269\|PubMed:14657427}.
Similarity:		Belongs to the IL-10 family. {ECO:0000305}.