IL10 (interleukin 10)

Gene

• Entrez ID: 3586
• Gene name: Interleukin 10
• Gene symbol: IL10
• Synonyms: CSIF, GVHDS, IL-10, IL10A, TGIF
• Chromosome: 1
• Chromosome location: 1q32.1
• Summary: The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis. [provided by RefSeq, May 2020]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005082	hsa-miR-106a-5p	Luciferase reporter assay, qRT-PCR	19307576
MIRT054365	hsa-let-7c-5p	Luciferase reporter assay, qRT-PCR	22835429
MIRT731372	hsa-miR-194-5p	Luciferase reporter assay, Microarray, qRT-PCR	26147452
MIRT732561	hsa-miR-98-5p	Luciferase reporter assay, qRT-PCR, Western blot	26367177
MIRT732561	hsa-miR-98-5p	qRT-PCR	27605397
MIRT733091	hsa-miR-19a-3p	ELISA, qRT-PCR, Western blot, ChIP	28386366
MIRT734014	hsa-miR-34a-5p	PCR array	28097098
MIRT734506	hsa-miR-503-3p	ELISA, qRT-PCR, MTT	26580839

Transcription factors

Transcription factor	Regulation	Reference
ATF1	Activation	10540320
CEBPA	Unknown	12219016
CEBPB	Unknown	12493739
CREB1	Activation	10540320;22140263
CREB1	Unknown	17202341
FLI1	Activation	20879862
FOXP3	Unknown	24315995
GATA3	Unknown	21507199
HDAC11	Repression	19011628
HDAC4	Repression	17610967
IRF1	Activation	12817009
IRF8	Unknown	20709027
MSC	Activation	19561533
NFKB1	Activation	19124729
NFKB1	Unknown	9310124
NR1I2	Activation	22285937
PARP1	Unknown	20181890
PGR	Repression	18685848
REL	Unknown	9310124
RELA	Activation	19124729
SP1	Activation	21309719
SP1	Unknown	11278848;17202341
STAT1	Unknown	20709027
STAT3	Activation	12817009;18765795
STAT3	Unknown	10903771;15034082;17404037;18403020;19124156
TBX21	Unknown	21507199
VDR	Repression	20691220

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001818	Process	Negative regulation of cytokine production	IDA	1940799
GO:0001819	Process	Positive regulation of cytokine production	IDA	10443688
GO:0001938	Process	Positive regulation of endothelial cell proliferation	IEA
GO:0002237	Process	Response to molecule of bacterial origin	IDA	17449476
GO:0002639	Process	Positive regulation of immunoglobulin production	IGI	22962438
GO:0002719	Process	Negative regulation of cytokine production involved in immune response	IDA	10443688
GO:0002875	Process	Negative regulation of chronic inflammatory response to antigenic stimulus	IEA
GO:0002904	Process	Positive regulation of B cell apoptotic process	IDA	9184696
GO:0005125	Function	Cytokine activity	NAS	10443688
GO:0005141	Function	Interleukin-10 receptor binding	NAS	1847510
GO:0005515	Function	Protein binding	IPI	11485736, 12513909, 15837194, 16982608, 20462497, 32296183
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IDA	10443688, 21323571
GO:0007253	Process	Cytoplasmic sequestering of NF-kappaB	NAS	10975994
GO:0007568	Process	Aging	IEA
GO:0008083	Function	Growth factor activity	NAS	1371884
GO:0008285	Process	Negative regulation of cell population proliferation	ISS
GO:0010468	Process	Regulation of gene expression	IDA	9184696
GO:0010507	Process	Negative regulation of autophagy	IDA	26962683
GO:0014823	Process	Response to activity	IEA
GO:0014854	Process	Response to inactivity	IEA
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0030097	Process	Hemopoiesis	TAS	11244051
GO:0030183	Process	B cell differentiation	NAS	8228801
GO:0030595	Process	Leukocyte chemotaxis	TAS	9405662
GO:0030886	Process	Negative regulation of myeloid dendritic cell activation	IEA
GO:0030889	Process	Negative regulation of B cell proliferation	IDA	9184696
GO:0032687	Process	Negative regulation of interferon-alpha production	NAS	9637497
GO:0032689	Process	Negative regulation of interferon-gamma production	IEA
GO:0032692	Process	Negative regulation of interleukin-1 production	TAS	19262501
GO:0032695	Process	Negative regulation of interleukin-12 production	TAS	19262501
GO:0032701	Process	Negative regulation of interleukin-18 production	TAS	19262501
GO:0032715	Process	Negative regulation of interleukin-6 production	IDA	10443688
GO:0032715	Process	Negative regulation of interleukin-6 production	TAS	19262501
GO:0032717	Process	Negative regulation of interleukin-8 production	TAS	19262501
GO:0032720	Process	Negative regulation of tumor necrosis factor production	TAS	19262501
GO:0032868	Process	Response to insulin	IEA
GO:0034115	Process	Negative regulation of heterotypic cell-cell adhesion	ISS
GO:0034116	Process	Positive regulation of heterotypic cell-cell adhesion	ISS
GO:0034465	Process	Response to carbon monoxide	IEA
GO:0035722	Process	Interleukin-12-mediated signaling pathway	TAS
GO:0035729	Process	Cellular response to hepatocyte growth factor stimulus	IEA
GO:0042092	Process	Type 2 immune response	TAS	11244051
GO:0042100	Process	B cell proliferation	NAS	8228801
GO:0042130	Process	Negative regulation of T cell proliferation	NAS	8499633, 14971032
GO:0042493	Process	Response to drug	IEA
GO:0042742	Process	Defense response to bacterium	IEA
GO:0042832	Process	Defense response to protozoan	IEA
GO:0043032	Process	Positive regulation of macrophage activation	IEA
GO:0043066	Process	Negative regulation of apoptotic process	NAS	8312229
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0045019	Process	Negative regulation of nitric oxide biosynthetic process	IEA
GO:0045191	Process	Regulation of isotype switching	NAS	8228801
GO:0045347	Process	Negative regulation of MHC class II biosynthetic process	IDA	1940799
GO:0045347	Process	Negative regulation of MHC class II biosynthetic process	TAS	11244051
GO:0045348	Process	Positive regulation of MHC class II biosynthetic process	IEA
GO:0045787	Process	Positive regulation of cell cycle	IEA
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	7749983, 16606666
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	17875732
GO:0045930	Process	Negative regulation of mitotic cell cycle	ISS
GO:0046427	Process	Positive regulation of receptor signaling pathway via JAK-STAT	IDA	16982608
GO:0046983	Function	Protein dimerization activity	IDA	16982608
GO:0050728	Process	Negative regulation of inflammatory response	IDA	10443688
GO:0050728	Process	Negative regulation of inflammatory response	NAS	21857966
GO:0050807	Process	Regulation of synapse organization	IEA
GO:0051045	Process	Negative regulation of membrane protein ectodomain proteolysis	IDA	18383040
GO:0051091	Process	Positive regulation of DNA-binding transcription factor activity	IDA	7749983
GO:0051384	Process	Response to glucocorticoid	IDA	10443688
GO:0060302	Process	Negative regulation of cytokine activity	IMP	9847016
GO:0060670	Process	Branching involved in labyrinthine layer morphogenesis	IEA
GO:0071222	Process	Cellular response to lipopolysaccharide	NAS	14971032
GO:0071392	Process	Cellular response to estradiol stimulus	IEA
GO:0071650	Process	Negative regulation of chemokine (C-C motif) ligand 5 production	TAS	19262501
GO:0072577	Process	Endothelial cell apoptotic process	ISS
GO:0097421	Process	Liver regeneration	IEA
GO:1900100	Process	Positive regulation of plasma cell differentiation	IGI	22962438
GO:1902895	Process	Positive regulation of pri-miRNA transcription by RNA polymerase II	IEA
GO:1903034	Process	Regulation of response to wounding	ISS
GO:1903208	Process	Negative regulation of hydrogen peroxide-induced neuron death	ISS
GO:1903659	Process	Regulation of complement-dependent cytotoxicity	IMP	16034134
GO:1903672	Process	Positive regulation of sprouting angiogenesis	IEA
GO:1904057	Process	Negative regulation of sensory perception of pain	IEA
GO:1904706	Process	Negative regulation of vascular associated smooth muscle cell proliferation	ISS
GO:1904707	Process	Positive regulation of vascular associated smooth muscle cell proliferation	ISS
GO:2000273	Process	Positive regulation of signaling receptor activity	IDA	10443688
GO:2000352	Process	Negative regulation of endothelial cell apoptotic process	IMP	16034134

Other IDs

• MIM: 124092
• HGNC: 5962
• e!Ensembl: ENSG00000136634

Protein

• UniProt ID: P22301
• Protein name: Interleukin-10 (IL-10) (Cytokine synthesis inhibitory factor) (CSIF)
• Protein 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).
• PDB: 1ILK, 1INR, 1J7V, 1LK3, 1Y6K, 2H24, 2ILK
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00726	IL10	5 → 174	Interleukin 10	Domain

• Sequence:

  MHSSALLCCLVLLTGVRASPGQGTQSENSCTHFPGNLPNMLRDLRDAFSRVKTFFQMKDQ
  LDNLLLKESLLEDFKGYLGCQALSEMIQFYLEEVMPQAENQDPDIKAHVNSLGENLKTLR
  LRLRRCHRFLPCENKSKAVEQVKNAFNKLQEKGIYKAMSEFDIFINYIEAYMTMKIRN

• Sequence length: 178