UniProtKB - P22301 (IL10_HUMAN)
Protein
Interleukin-10
Gene
IL10
Organism
Homo sapiens (Human)
Status
Functioni
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).By similarity6 Publications
GO - Molecular functioni
- cytokine activity Source: BHF-UCL
- growth factor activity Source: UniProtKB
- interleukin-10 receptor binding Source: UniProtKB
- protein dimerization activity Source: UniProtKB
GO - Biological processi
- aging Source: Ensembl
- B cell differentiation Source: UniProtKB
- B cell proliferation Source: UniProtKB
- branching involved in labyrinthine layer morphogenesis Source: Ensembl
- cellular response to estradiol stimulus Source: Ensembl
- cellular response to hepatocyte growth factor stimulus Source: Ensembl
- cellular response to lipopolysaccharide Source: BHF-UCL
- cytokine-mediated signaling pathway Source: Reactome
- cytoplasmic sequestering of NF-kappaB Source: UniProtKB
- defense response to bacterium Source: Ensembl
- defense response to protozoan Source: Ensembl
- endothelial cell apoptotic process Source: BHF-UCL
- hemopoiesis Source: UniProtKB
- inflammatory response Source: BHF-UCL
- interleukin-12-mediated signaling pathway Source: Reactome
- leukocyte chemotaxis Source: ProtInc
- liver regeneration Source: Ensembl
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of autophagy Source: UniProtKB
- negative regulation of B cell proliferation Source: MGI
- negative regulation of cell population proliferation Source: BHF-UCL
- negative regulation of chemokine (C-C motif) ligand 5 production Source: AgBase
- negative regulation of chronic inflammatory response to antigenic stimulus Source: Ensembl
- negative regulation of cytokine activity Source: CACAO
- negative regulation of cytokine production Source: UniProtKB
- negative regulation of cytokine secretion involved in immune response Source: BHF-UCL
- negative regulation of heterotypic cell-cell adhesion Source: BHF-UCL
- negative regulation of hydrogen peroxide-induced neuron death Source: ARUK-UCL
- negative regulation of inflammatory response Source: ARUK-UCL
- negative regulation of interferon-alpha biosynthetic process Source: UniProtKB
- negative regulation of interferon-gamma production Source: Ensembl
- negative regulation of interleukin-12 production Source: AgBase
- negative regulation of interleukin-18 production Source: AgBase
- negative regulation of interleukin-1 production Source: AgBase
- negative regulation of interleukin-6 production Source: BHF-UCL
- negative regulation of interleukin-8 production Source: AgBase
- negative regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
- negative regulation of MHC class II biosynthetic process Source: UniProtKB
- negative regulation of mitotic cell cycle Source: BHF-UCL
- negative regulation of myeloid dendritic cell activation Source: Ensembl
- negative regulation of nitric oxide biosynthetic process Source: Ensembl
- negative regulation of sensory perception of pain Source: Ensembl
- negative regulation of T cell proliferation Source: UniProtKB
- negative regulation of tumor necrosis factor biosynthetic process Source: Ensembl
- negative regulation of tumor necrosis factor production Source: AgBase
- negative regulation of vascular smooth muscle cell proliferation Source: BHF-UCL
- positive regulation of B cell apoptotic process Source: MGI
- positive regulation of cell cycle Source: Ensembl
- positive regulation of cytokine secretion Source: BHF-UCL
- positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
- positive regulation of endothelial cell proliferation Source: Ensembl
- positive regulation of heterotypic cell-cell adhesion Source: BHF-UCL
- positive regulation of macrophage activation Source: Ensembl
- positive regulation of MHC class II biosynthetic process Source: Ensembl
- positive regulation of pri-miRNA transcription by RNA polymerase II Source: Ensembl
- positive regulation of receptor signaling pathway via JAK-STAT Source: UniProtKB
- positive regulation of sprouting angiogenesis Source: Ensembl
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of vascular smooth muscle cell proliferation Source: BHF-UCL
- receptor biosynthetic process Source: BHF-UCL
- regulation of gene expression Source: MGI
- regulation of isotype switching Source: UniProtKB
- regulation of response to wounding Source: BHF-UCL
- regulation of synapse organization Source: Ensembl
- response to activity Source: Ensembl
- response to carbon monoxide Source: Ensembl
- response to glucocorticoid Source: BHF-UCL
- response to inactivity Source: Ensembl
- response to insulin Source: Ensembl
- response to molecule of bacterial origin Source: UniProtKB
- type 2 immune response Source: UniProtKB
Keywordsi
Molecular function | Cytokine |
Enzyme and pathway databases
Reactomei | R-HSA-6783783 Interleukin-10 signaling R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation |
SignaLinki | P22301 |
SIGNORi | P22301 |
Names & Taxonomyi
Protein namesi | Recommended name: Interleukin-10Short name: IL-10 Alternative name(s): Cytokine synthesis inhibitory factor Short name: CSIF |
Gene namesi | Name:IL10 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5962 IL10 |
MIMi | 124092 gene |
neXtProti | NX_P22301 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: BHF-UCL
Keywords - Cellular componenti
SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 42 | R → A: About 80% loss of IL10RA binding. 1 Publication | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 3586 |
MalaCardsi | IL10 |
MIMi | 614395 phenotype |
OpenTargetsi | ENSG00000136634 |
Orphaneti | 117 Behcet disease 238569 Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome 536 Systemic lupus erythematosus |
PharmGKBi | PA29778 |
Miscellaneous databases
Pharosi | P22301 |
Chemistry databases
ChEMBLi | CHEMBL3712920 |
DrugBanki | DB05744 CRx-139 DB05771 LLL-3348 |
Polymorphism and mutation databases
BioMutai | IL10 |
DMDMi | 124292 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 18 | 1 PublicationAdd BLAST | 18 | |
ChainiPRO_0000015360 | 19 – 178 | Interleukin-10Add BLAST | 160 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 30 ↔ 126 | 1 Publication | ||
Disulfide bondi | 80 ↔ 132 | 1 Publication | ||
Glycosylationi | 134 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
MassIVEi | P22301 |
PaxDbi | P22301 |
PeptideAtlasi | P22301 |
PRIDEi | P22301 |
ProteomicsDBi | 53970 |
Expressioni
Tissue specificityi
Produced by a variety of cell lines, including T-cells, macrophages, mast cells and other cell types.2 Publications
Gene expression databases
Bgeei | ENSG00000136634 Expressed in 81 organ(s), highest expression level in esophagus |
ExpressionAtlasi | P22301 baseline and differential |
Genevisiblei | P22301 HS |
Organism-specific databases
HPAi | CAB013120 |
Interactioni
Subunit structurei
Binary interactionsi
GO - Molecular functioni
- cytokine activity Source: BHF-UCL
- growth factor activity Source: UniProtKB
- interleukin-10 receptor binding Source: UniProtKB
- protein dimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGridi | 109800, 7 interactors |
CORUMi | P22301 |
DIPi | DIP-3511N |
IntActi | P22301, 8 interactors |
MINTi | P22301 |
STRINGi | 9606.ENSP00000412237 |
Chemistry databases
BindingDBi | P22301 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P22301 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P22301 |
Family & Domainsi
Sequence similaritiesi
Belongs to the IL-10 family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG410IYFW Eukaryota ENOG4111PXC LUCA |
GeneTreei | ENSGT00950000183124 |
HOGENOMi | HOG000072692 |
InParanoidi | P22301 |
KOi | K05443 |
OMAi | MIQFYLV |
OrthoDBi | 1389566at2759 |
PhylomeDBi | P22301 |
TreeFami | TF333253 |
Family and domain databases
InterProi | View protein in InterPro IPR009079 4_helix_cytokine-like_core IPR000098 IL-10 IPR020443 IL-10/19/20/22/24/26_fam IPR020423 IL-10_CS |
Pfami | View protein in Pfam PF00726 IL10, 1 hit |
PRINTSi | PR01294 INTRLEUKIN10 |
SMARTi | View protein in SMART SM00188 IL10, 1 hit |
SUPFAMi | SSF47266 SSF47266, 1 hit |
PROSITEi | View protein in PROSITE PS00520 INTERLEUKIN_10, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
P22301-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MHSSALLCCL VLLTGVRASP GQGTQSENSC THFPGNLPNM LRDLRDAFSR
60 70 80 90 100
VKTFFQMKDQ LDNLLLKESL LEDFKGYLGC QALSEMIQFY LEEVMPQAEN
110 120 130 140 150
QDPDIKAHVN SLGENLKTLR LRLRRCHRFL PCENKSKAVE QVKNAFNKLQ
160 170
EKGIYKAMSE FDIFINYIEA YMTMKIRN
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A286YEX3 | A0A286YEX3_HUMAN | Interleukin-10 | IL10 | 74 | Annotation score: | ||
A0A590UK12 | A0A590UK12_HUMAN | Interleukin-10 | IL10 | 139 | Annotation score: |
Polymorphismi
A polymorphism in IL10 promoter region is associated with resistance to graft-versus-host disease (GVHDS) [MIMi: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.1 Publication
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_015883 | 15 | G → R in a family affected by Crohn disease; decreases secretion thereby reducing the anti-inflammatory effect. 1 PublicationCorresponds to variant dbSNP:rs145922845EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M57627 mRNA Translation: AAA63207.1 U16720 Genomic DNA Translation: AAA80104.1 AY029171 mRNA Translation: AAK38162.1 AF418271 Genomic DNA Translation: AAL06594.1 |
CCDSi | CCDS1467.1 |
PIRi | A38580 |
RefSeqi | NP_000563.1, NM_000572.2 |
Genome annotation databases
Ensembli | ENST00000423557; ENSP00000412237; ENSG00000136634 |
GeneIDi | 3586 |
KEGGi | hsa:3586 |
Similar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Interleukin-10 entry |
SeattleSNPs |
SHMPD The Singapore human mutation and polymorphism database |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M57627 mRNA Translation: AAA63207.1 U16720 Genomic DNA Translation: AAA80104.1 AY029171 mRNA Translation: AAK38162.1 AF418271 Genomic DNA Translation: AAL06594.1 |
CCDSi | CCDS1467.1 |
PIRi | A38580 |
RefSeqi | NP_000563.1, NM_000572.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1ILK | X-ray | 1.80 | A | 28-178 | [»] | |
1INR | X-ray | 2.00 | A | 19-178 | [»] | |
1J7V | X-ray | 2.90 | L | 19-178 | [»] | |
1LK3 | X-ray | 1.91 | A/B | 26-178 | [»] | |
1Y6K | X-ray | 2.52 | L | 19-178 | [»] | |
2H24 | X-ray | 2.00 | A | 19-178 | [»] | |
2ILK | X-ray | 1.60 | A | 19-178 | [»] | |
SMRi | P22301 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGridi | 109800, 7 interactors |
CORUMi | P22301 |
DIPi | DIP-3511N |
IntActi | P22301, 8 interactors |
MINTi | P22301 |
STRINGi | 9606.ENSP00000412237 |
Chemistry databases
BindingDBi | P22301 |
ChEMBLi | CHEMBL3712920 |
DrugBanki | DB05744 CRx-139 DB05771 LLL-3348 |
Polymorphism and mutation databases
BioMutai | IL10 |
DMDMi | 124292 |
Proteomic databases
MassIVEi | P22301 |
PaxDbi | P22301 |
PeptideAtlasi | P22301 |
PRIDEi | P22301 |
ProteomicsDBi | 53970 |
Protocols and materials databases
ABCDi | P22301 |
DNASUi | 3586 |
Genome annotation databases
Ensembli | ENST00000423557; ENSP00000412237; ENSG00000136634 |
GeneIDi | 3586 |
KEGGi | hsa:3586 |
Organism-specific databases
CTDi | 3586 |
DisGeNETi | 3586 |
GeneCardsi | IL10 |
HGNCi | HGNC:5962 IL10 |
HPAi | CAB013120 |
MalaCardsi | IL10 |
MIMi | 124092 gene 614395 phenotype |
neXtProti | NX_P22301 |
OpenTargetsi | ENSG00000136634 |
Orphaneti | 117 Behcet disease 238569 Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome 536 Systemic lupus erythematosus |
PharmGKBi | PA29778 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG410IYFW Eukaryota ENOG4111PXC LUCA |
GeneTreei | ENSGT00950000183124 |
HOGENOMi | HOG000072692 |
InParanoidi | P22301 |
KOi | K05443 |
OMAi | MIQFYLV |
OrthoDBi | 1389566at2759 |
PhylomeDBi | P22301 |
TreeFami | TF333253 |
Enzyme and pathway databases
Reactomei | R-HSA-6783783 Interleukin-10 signaling R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation |
SignaLinki | P22301 |
SIGNORi | P22301 |
Miscellaneous databases
ChiTaRSi | IL10 human |
EvolutionaryTracei | P22301 |
GeneWikii | Interleukin_10 |
GenomeRNAii | 3586 |
Pharosi | P22301 |
PROi | PR:P22301 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000136634 Expressed in 81 organ(s), highest expression level in esophagus |
ExpressionAtlasi | P22301 baseline and differential |
Genevisiblei | P22301 HS |
Family and domain databases
InterProi | View protein in InterPro IPR009079 4_helix_cytokine-like_core IPR000098 IL-10 IPR020443 IL-10/19/20/22/24/26_fam IPR020423 IL-10_CS |
Pfami | View protein in Pfam PF00726 IL10, 1 hit |
PRINTSi | PR01294 INTRLEUKIN10 |
SMARTi | View protein in SMART SM00188 IL10, 1 hit |
SUPFAMi | SSF47266 SSF47266, 1 hit |
PROSITEi | View protein in PROSITE PS00520 INTERLEUKIN_10, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | IL10_HUMAN | |
Accessioni | P22301Primary (citable) accession number: P22301 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1991 |
Last sequence update: | August 1, 1991 | |
Last modified: | October 16, 2019 | |
This is version 199 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - SIMILARITY comments
Index of protein domains and families - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references