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Protein

Interleukin-10

Gene

IL10

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T-cells.

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL
  • growth factor activity Source: UniProtKB
  • interleukin-10 receptor binding 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
  • cell-cell signaling Source: UniProtKB
  • cellular response to estradiol stimulus Source: Ensembl
  • cellular response to lipopolysaccharide Source: BHF-UCL
  • cytoplasmic sequestering of NF-kappaB Source: UniProtKB
  • defense response to bacterium Source: Ensembl
  • hemopoiesis Source: UniProtKB
  • inflammatory response Source: BHF-UCL
  • leukocyte chemotaxis Source: ProtInc
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of B cell proliferation Source: MGI
  • negative regulation of chronic inflammatory response to antigenic stimulus Source: Ensembl
  • negative regulation of cytokine activity Source: CACAO
  • negative regulation of cytokine secretion involved in immune response Source: BHF-UCL
  • negative regulation of growth of symbiont in host Source: Ensembl
  • negative regulation of interferon-alpha biosynthetic process Source: UniProtKB
  • negative regulation of interferon-gamma production Source: Ensembl
  • negative regulation of interleukin-12 production Source: Ensembl
  • negative regulation of interleukin-6 production Source: BHF-UCL
  • negative regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
  • negative regulation of MHC class II biosynthetic process Source: UniProtKB
  • negative regulation of myeloid dendritic cell activation Source: Ensembl
  • negative regulation of nitric oxide biosynthetic process Source: Ensembl
  • negative regulation of T cell proliferation Source: UniProtKB
  • negative regulation of tumor necrosis factor biosynthetic process Source: Ensembl
  • positive regulation of B cell apoptotic process Source: MGI
  • positive regulation of cytokine secretion Source: BHF-UCL
  • positive regulation of JAK-STAT cascade Source: GO_Central
  • positive regulation of MHC class II biosynthetic process Source: Ensembl
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • receptor biosynthetic process Source: BHF-UCL
  • regulation of gene expression Source: MGI
  • regulation of isotype switching Source: UniProtKB
  • regulation of sensory perception of pain Source: Ensembl
  • response to activity Source: Ensembl
  • response to carbon monoxide Source: Ensembl
  • response to drug 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
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Enzyme and pathway databases

SignaLinkiP22301.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-10
Short name:
IL-10
Alternative name(s):
Cytokine synthesis inhibitory factor
Short name:
CSIF
Gene namesi
Name:IL10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:5962. IL10.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GOC
  • extracellular space Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi614395. phenotype.
Orphaneti238569. Autosomal recessive early-onset inflammatory bowel disease.
117. Behcet disease.
536. Systemic lupus erythematosus.
PharmGKBiPA29778.

Polymorphism and mutation databases

BioMutaiIL10.
DMDMi124292.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 18181 PublicationAdd
BLAST
Chaini19 – 178160Interleukin-10PRO_0000015360Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi30 ↔ 1261 Publication
Disulfide bondi80 ↔ 1321 Publication
Glycosylationi134 – 1341N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP22301.
PRIDEiP22301.

PTM databases

PhosphoSiteiP22301.

Expressioni

Tissue specificityi

Produced by a variety of cell lines, including T-cells, macrophages, mast cells and other cell types.

Gene expression databases

BgeeiP22301.
CleanExiHS_IL10.
ExpressionAtlasiP22301. baseline and differential.
GenevisibleiP22301. HS.

Organism-specific databases

HPAiCAB013120.

Interactioni

Subunit structurei

Homodimer.2 Publications

Protein-protein interaction databases

BioGridi109800. 3 interactions.
DIPiDIP-3511N.
IntActiP22301. 2 interactions.
MINTiMINT-206740.
STRINGi9606.ENSP00000412237.

Structurei

Secondary structure

1
178
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni33 – 364Combined sources
Helixi37 – 4913Combined sources
Helixi52 – 587Combined sources
Helixi68 – 758Combined sources
Turni76 – 783Combined sources
Helixi79 – 9315Combined sources
Helixi95 – 995Combined sources
Turni103 – 1053Combined sources
Helixi106 – 12520Combined sources
Helixi127 – 1293Combined sources
Helixi131 – 1333Combined sources
Helixi137 – 14812Combined sources
Helixi151 – 1599Combined sources
Helixi161 – 17616Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ILKX-ray1.80A28-178[»]
1INRX-ray2.00A19-178[»]
1J7VX-ray2.90L19-178[»]
1LK3X-ray1.91A/B26-178[»]
1Y6KX-ray2.52L19-178[»]
2H24X-ray2.00A19-178[»]
2ILKX-ray1.60A19-178[»]
ProteinModelPortaliP22301.
SMRiP22301. Positions 24-178.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22301.

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-10 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG43085.
HOGENOMiHOG000072692.
HOVERGENiHBG004110.
InParanoidiP22301.
KOiK05443.
OMAiPHMLREL.
OrthoDBiEOG7C2R33.
PhylomeDBiP22301.
TreeFamiTF333253.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000098. IL-10.
IPR020443. IL-10/19/20/24/26_fam.
IPR020423. IL-10_CS.
[Graphical view]
PANTHERiPTHR11585. PTHR11585. 1 hit.
PfamiPF00726. IL10. 1 hit.
[Graphical view]
PRINTSiPR01294. INTRLEUKIN10.
SMARTiSM00188. IL10. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00520. INTERLEUKIN_10. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P22301-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:178
Mass (Da):20,517
Last modified:August 1, 1991 - v1
Checksum:i6825E9FA4337CDE4
GO

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti15 – 151G → R in a family affected by Crohn disease; decreases secretion thereby reducing the anti-inflammatory effect. 1 Publication
VAR_015883

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.
CCDSiCCDS1467.1.
PIRiA38580.
RefSeqiNP_000563.1. NM_000572.2.
UniGeneiHs.193717.

Genome annotation databases

EnsembliENST00000423557; ENSP00000412237; ENSG00000136634.
GeneIDi3586.
KEGGihsa:3586.
UCSCiuc001hen.1. human.

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.
CCDSiCCDS1467.1.
PIRiA38580.
RefSeqiNP_000563.1. NM_000572.2.
UniGeneiHs.193717.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ILKX-ray1.80A28-178[»]
1INRX-ray2.00A19-178[»]
1J7VX-ray2.90L19-178[»]
1LK3X-ray1.91A/B26-178[»]
1Y6KX-ray2.52L19-178[»]
2H24X-ray2.00A19-178[»]
2ILKX-ray1.60A19-178[»]
ProteinModelPortaliP22301.
SMRiP22301. Positions 24-178.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109800. 3 interactions.
DIPiDIP-3511N.
IntActiP22301. 2 interactions.
MINTiMINT-206740.
STRINGi9606.ENSP00000412237.

PTM databases

PhosphoSiteiP22301.

Polymorphism and mutation databases

BioMutaiIL10.
DMDMi124292.

Proteomic databases

PaxDbiP22301.
PRIDEiP22301.

Protocols and materials databases

DNASUi3586.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000423557; ENSP00000412237; ENSG00000136634.
GeneIDi3586.
KEGGihsa:3586.
UCSCiuc001hen.1. human.

Organism-specific databases

CTDi3586.
GeneCardsiGC01M206940.
HGNCiHGNC:5962. IL10.
HPAiCAB013120.
MIMi124092. gene.
614395. phenotype.
neXtProtiNX_P22301.
Orphaneti238569. Autosomal recessive early-onset inflammatory bowel disease.
117. Behcet disease.
536. Systemic lupus erythematosus.
PharmGKBiPA29778.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG43085.
HOGENOMiHOG000072692.
HOVERGENiHBG004110.
InParanoidiP22301.
KOiK05443.
OMAiPHMLREL.
OrthoDBiEOG7C2R33.
PhylomeDBiP22301.
TreeFamiTF333253.

Enzyme and pathway databases

SignaLinkiP22301.

Miscellaneous databases

EvolutionaryTraceiP22301.
GeneWikiiInterleukin_10.
GenomeRNAii3586.
NextBioi14011.
PROiP22301.
SOURCEiSearch...

Gene expression databases

BgeeiP22301.
CleanExiHS_IL10.
ExpressionAtlasiP22301. baseline and differential.
GenevisibleiP22301. HS.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR000098. IL-10.
IPR020443. IL-10/19/20/24/26_fam.
IPR020423. IL-10_CS.
[Graphical view]
PANTHERiPTHR11585. PTHR11585. 1 hit.
PfamiPF00726. IL10. 1 hit.
[Graphical view]
PRINTSiPR01294. INTRLEUKIN10.
SMARTiSM00188. IL10. 1 hit.
[Graphical view]
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00520. INTERLEUKIN_10. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI."
    Vieira P., de Waal-Malefyt R., Dang M.-N., Johnson K.E., Kastelein R., Fiorentino D.F., Devries J.E., Roncarolo M.-G., Mosmann T.R., Moore K.W.
    Proc. Natl. Acad. Sci. U.S.A. 88:1172-1176(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: T-cell.
  2. "The structure of the human IL-10 gene."
    Sanjanwala B., de Waal-Malefyt R.
    Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Cloning, sequencing of human interleukin-10 cDNA and construction of its eukaryotic expression vector."
    Dai W.-J., Jiang H.-C., Pan S.-H.
    Haerbin Yi Ke Da Xue Xue Bao 35:4-6(2001)
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. SeattleSNPs variation discovery resource
    Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. Cited for: PROTEIN SEQUENCE OF 26-34 AND 170-178.
  6. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
    Zhang Z., Henzel W.J.
    Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 19-33.
  7. "Disulfide bond assignments and secondary structure analysis of human and murine interleukin 10."
    Windsor W.T., Syto R., Tsarbopoulos A., Zhang R., Durkin J., Baldwin S., Paliwal S., Mui P.W., Pramanik B., Trotta P.P.
    Biochemistry 32:8807-8815(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.
  8. "Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation."
    Lin M.T., Storer B., Martin P.J., Tseng L.H., Gooley T., Chen P.J., Hansen J.A.
    N. Engl. J. Med. 349:2201-2210(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN RESISTANCE TO GVHDS.
  9. "Crystal structure of interleukin 10 reveals an interferon gamma-like fold."
    Walter M.R., Nagabhushan T.L.
    Biochemistry 34:12118-12125(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
  10. "Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma."
    Zdanov A., Schalk-Hihi C., Gustchina A., Tsang M., Wheatherbee J., Wlodawer A.
    Structure 3:591-601(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
  11. "Crystal structure of human interleukin-10 at 1.6-A resolution and a model of a complex with its soluble receptor."
    Zdanov A., Schalk-Hihi C., Wlodawer A.
    Protein Sci. 5:1955-1962(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
  12. "Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site."
    Josephson K., Logsdon N.J., Walter M.R.
    Immunity 15:35-46(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 19-178 IN COMPLEX WITH IL10R1.
  13. "Same structure, different function crystal structure of the Epstein-Barr virus IL-10 bound to the soluble IL-10R1 chain."
    Yoon S.I., Jones B.C., Logsdon N.J., Walter M.R.
    Structure 13:551-564(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 19-178 IN COMPLEX WITH IL10R1.
  14. "A Gly15Arg mutation in the interleukin-10 gene reduces secretion of interleukin-10 in Crohn disease."
    van der Linde K., Boor P.P., Sandkuijl L.A., Meijssen M.A., Savelkoul H.F., Wilson J.H., de Rooij F.W.
    Scand. J. Gastroenterol. 38:611-617(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ARG-15.

Entry informationi

Entry nameiIL10_HUMAN
AccessioniPrimary (citable) accession number: P22301
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: June 24, 2015
This is version 161 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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 proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.