UniProtKB - P22301 (IL10_HUMAN)
Interleukin-10
IL10
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 PublicationsGO - 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: ARUK-UCL
- 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
- 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 production 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: BHF-UCL
- negative regulation of interferon-alpha production 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 neuron apoptotic process 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 production Source: AgBase
- negative regulation of vascular associated 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 production 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 immunoglobulin production Source: ARUK-UCL
- positive regulation of macrophage activation Source: Ensembl
- positive regulation of MHC class II biosynthetic process Source: Ensembl
- positive regulation of plasma cell differentiation Source: ARUK-UCL
- positive regulation of pri-miRNA transcription by RNA polymerase II Source: ARUK-UCL
- positive regulation of receptor signaling pathway via JAK-STAT Source: UniProtKB
- positive regulation of signaling receptor activity Source: BHF-UCL
- positive regulation of sprouting angiogenesis Source: Ensembl
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of vascular associated smooth muscle cell proliferation 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
- response to xenobiotic stimulus Source: Ensembl
- type 2 immune response Source: UniProtKB
Keywordsi
Molecular function | Cytokine |
Enzyme and pathway databases
PathwayCommonsi | P22301 |
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 R-HSA-9662834, CD163 mediating an anti-inflammatory response R-HSA-9664323, FCGR3A-mediated IL10 synthesis |
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 |
VEuPathDBi | HostDB:ENSG00000136634 |
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 variantOrganism-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, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3712920 |
DrugBanki | DB05744, CRx-139 DB05771, LLL-3348 |
Genetic variation 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 |
PTM databases
GlyGeni | P22301, 1 site |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000136634, Expressed in esophagus and 108 other tissues |
ExpressionAtlasi | P22301, baseline and differential |
Genevisiblei | P22301, HS |
Organism-specific databases
HPAi | ENSG00000136634, Tissue enhanced (adipose tissue, lymphoid tissue) |
Interactioni
Subunit structurei
Binary interactionsi
P22301
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, 19 interactors |
CORUMi | P22301 |
DIPi | DIP-3511N |
IntActi | P22301, 8 interactors |
MINTi | P22301 |
STRINGi | 9606.ENSP00000412237 |
Chemistry databases
BindingDBi | P22301 |
Miscellaneous databases
RNActi | P22301, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P22301 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P22301 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502S22U, Eukaryota |
GeneTreei | ENSGT00950000183124 |
HOGENOMi | CLU_127747_0_0_1 |
InParanoidi | P22301 |
OMAi | MIQFYLV |
OrthoDBi | 651627at2759 |
PhylomeDBi | P22301 |
TreeFami | TF333253 |
Family and domain databases
Gene3Di | 1.20.1250.10, 1 hit |
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
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 family protein | IL10 | 74 | Annotation score: | ||
A0A590UK12 | A0A590UK12_HUMAN | Interleukin family protein | IL10 | 139 | Annotation score: |
Polymorphismi
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 |
MANE-Selecti | ENST00000423557.1; ENSP00000412237.1; NM_000572.3; NP_000563.1 |
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 | [»] | |
6X93 | electron microscopy | 3.50 | A/D | 19-178 | [»] | |
SMRi | P22301 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109800, 19 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 |
PTM databases
GlyGeni | P22301, 1 site |
Genetic variation databases
BioMutai | IL10 |
DMDMi | 124292 |
Proteomic databases
MassIVEi | P22301 |
PaxDbi | P22301 |
PeptideAtlasi | P22301 |
PRIDEi | P22301 |
ProteomicsDBi | 53970 |
Protocols and materials databases
ABCDi | P22301, 1 sequenced antibody |
Antibodypediai | 3407, 1720 antibodies from 46 providers |
DNASUi | 3586 |
Genome annotation databases
Ensembli | ENST00000423557; ENSP00000412237; ENSG00000136634 |
GeneIDi | 3586 |
KEGGi | hsa:3586 |
MANE-Selecti | ENST00000423557.1; ENSP00000412237.1; NM_000572.3; NP_000563.1 |
Organism-specific databases
CTDi | 3586 |
DisGeNETi | 3586 |
GeneCardsi | IL10 |
HGNCi | HGNC:5962, IL10 |
HPAi | ENSG00000136634, Tissue enhanced (adipose tissue, lymphoid tissue) |
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 |
VEuPathDBi | HostDB:ENSG00000136634 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S22U, Eukaryota |
GeneTreei | ENSGT00950000183124 |
HOGENOMi | CLU_127747_0_0_1 |
InParanoidi | P22301 |
OMAi | MIQFYLV |
OrthoDBi | 651627at2759 |
PhylomeDBi | P22301 |
TreeFami | TF333253 |
Enzyme and pathway databases
PathwayCommonsi | P22301 |
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 R-HSA-9662834, CD163 mediating an anti-inflammatory response R-HSA-9664323, FCGR3A-mediated IL10 synthesis |
SignaLinki | P22301 |
SIGNORi | P22301 |
Miscellaneous databases
BioGRID-ORCSi | 3586, 3 hits in 1034 CRISPR screens |
ChiTaRSi | IL10, human |
EvolutionaryTracei | P22301 |
GeneWikii | Interleukin_10 |
GenomeRNAii | 3586 |
Pharosi | P22301, Tbio |
PROi | PR:P22301 |
RNActi | P22301, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000136634, Expressed in esophagus and 108 other tissues |
ExpressionAtlasi | P22301, baseline and differential |
Genevisiblei | P22301, HS |
Family and domain databases
Gene3Di | 1.20.1250.10, 1 hit |
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 |
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: | February 23, 2022 | |
This is version 211 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, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - 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 - SIMILARITY comments
Index of protein domains and families