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P22301 (IL10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-10

Short name=IL-10
Alternative name(s):
Cytokine synthesis inhibitory factor
Short name=CSIF
Gene names
Name:IL10
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length178 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Homodimer.

Subcellular location

Secreted.

Tissue specificity

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

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.

Sequence similarities

Belongs to the IL-10 family.

Ontologies

Keywords
   Cellular componentSecreted
   DiseaseDisease mutation
   DomainSignal
   Molecular functionCytokine
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

Non-traceable author statement PubMed 8228801. Source: UniProtKB

B cell proliferation

Non-traceable author statement PubMed 8228801. Source: UniProtKB

branching involved in labyrinthine layer morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell-cell signaling

Inferred by curator Ref.1. Source: UniProtKB

cellular response to estradiol stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to lipopolysaccharide

Non-traceable author statement PubMed 14971032. Source: BHF-UCL

cytoplasmic sequestering of NF-kappaB

Non-traceable author statement PubMed 10975994. Source: UniProtKB

defense response to bacterium

Inferred from electronic annotation. Source: Ensembl

hemopoiesis

Traceable author statement PubMed 11244051. Source: UniProtKB

inflammatory response

Inferred from direct assay PubMed 10443688. Source: BHF-UCL

leukocyte chemotaxis

Traceable author statement Ref.5. Source: ProtInc

negative regulation of B cell proliferation

Inferred from direct assay PubMed 9184696. Source: MGI

negative regulation of MHC class II biosynthetic process

Traceable author statement PubMed 11244051. Source: UniProtKB

negative regulation of T cell proliferation

Non-traceable author statement PubMed 8499633. Source: UniProtKB

negative regulation of apoptotic process

Non-traceable author statement PubMed 8312229. Source: UniProtKB

negative regulation of chronic inflammatory response to antigenic stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of cytokine secretion involved in immune response

Inferred from direct assay PubMed 10443688. Source: BHF-UCL

negative regulation of growth of symbiont in host

Inferred from electronic annotation. Source: Ensembl

negative regulation of interferon-alpha biosynthetic process

Non-traceable author statement PubMed 9637497. Source: UniProtKB

negative regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-12 production

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-6 production

Inferred from direct assay PubMed 10443688. Source: BHF-UCL

negative regulation of membrane protein ectodomain proteolysis

Inferred from direct assay PubMed 18383040. Source: BHF-UCL

negative regulation of myeloid dendritic cell activation

Inferred from electronic annotation. Source: Ensembl

negative regulation of nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of tumor necrosis factor biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of tumor necrosis factor production

Inferred from electronic annotation. Source: Ensembl

positive regulation of B cell apoptotic process

Inferred from direct assay PubMed 9184696. Source: MGI

positive regulation of MHC class II biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytokine secretion

Inferred from direct assay PubMed 10443688. Source: BHF-UCL

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 7749983. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 7749983. Source: BHF-UCL

receptor biosynthetic process

Inferred from direct assay PubMed 10443688. Source: BHF-UCL

regulation of gene expression

Inferred from direct assay PubMed 9184696. Source: MGI

regulation of isotype switching

Non-traceable author statement PubMed 8228801. Source: UniProtKB

regulation of sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

response to activity

Inferred from electronic annotation. Source: Ensembl

response to carbon monoxide

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from direct assay PubMed 10443688. Source: BHF-UCL

response to inactivity

Inferred from electronic annotation. Source: Ensembl

response to insulin

Inferred from electronic annotation. Source: Ensembl

response to molecule of bacterial origin

Inferred from direct assay PubMed 17449476. Source: UniProtKB

type 2 immune response

Traceable author statement PubMed 11244051. Source: UniProtKB

   Cellular_componentextracellular space

Inferred from direct assay PubMed 10443688. Source: BHF-UCL

   Molecular_functioncytokine activity

Non-traceable author statement PubMed 10443688. Source: BHF-UCL

growth factor activity

Non-traceable author statement PubMed 1371884. Source: UniProtKB

interleukin-10 receptor binding

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.6
Chain19 – 178160Interleukin-10
PRO_0000015360

Amino acid modifications

Glycosylation1341N-linked (GlcNAc...) Potential
Disulfide bond30 ↔ 126 Ref.7
Disulfide bond80 ↔ 132 Ref.7

Natural variations

Natural variant151G → R in a family affected by Crohn disease; decreases secretion thereby reducing the anti-inflammatory effect. Ref.14
VAR_015883

Secondary structure

......................... 178
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P22301 [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: 6825E9FA4337CDE4

FASTA17820,517
        10         20         30         40         50         60 
MHSSALLCCL VLLTGVRASP GQGTQSENSC THFPGNLPNM LRDLRDAFSR VKTFFQMKDQ 

        70         80         90        100        110        120 
LDNLLLKESL LEDFKGYLGC QALSEMIQFY LEEVMPQAEN QDPDIKAHVN SLGENLKTLR 

       130        140        150        160        170 
LRLRRCHRFL PCENKSKAVE QVKNAFNKLQ EKGIYKAMSE FDIFINYIEA YMTMKIRN 

« Hide

References

[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]"Identification of functional domains on human interleukin 10."
Gesser B., Leffers H., Jinquan T., Vestergaard C., Kirstein N., Sindet-Pedersen S., Jensen S.L., Thestrup-Pedersen K., Larsen C.G.
Proc. Natl. Acad. Sci. U.S.A. 94:14620-14625(1997) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Wikipedia

Interleukin-10 entry

SeattleSNPs
SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M57627 mRNA. Translation: AAA63207.1.
U16720 Genomic DNA. Translation: AAA80104.1.
AY029171 mRNA. Translation: AAK38162.1.
AF418271 Genomic DNA. Translation: AAL06594.1.
PIRA38580.
RefSeqNP_000563.1. NM_000572.2.
UniGeneHs.193717.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP22301.
SMRP22301. Positions 24-178.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109800. 3 interactions.
DIPDIP-3511N.
IntActP22301. 1 interaction.
MINTMINT-206740.
STRING9606.ENSP00000412237.

PTM databases

PhosphoSiteP22301.

Polymorphism databases

DMDM124292.

Proteomic databases

PaxDbP22301.
PRIDEP22301.

Protocols and materials databases

DNASU3586.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000423557; ENSP00000412237; ENSG00000136634.
GeneID3586.
KEGGhsa:3586.
UCSCuc001hen.1. human.

Organism-specific databases

CTD3586.
GeneCardsGC01M206940.
HGNCHGNC:5962. IL10.
HPACAB013120.
MIM124092. gene.
614395. phenotype.
neXtProtNX_P22301.
Orphanet238569. Autosomal recessive early-onset inflammatory bowel disease.
117. Behcet disease.
206. Crohn disease.
536. Systemic lupus erythematosus.
PharmGKBPA29778.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43085.
HOGENOMHOG000072692.
HOVERGENHBG004110.
InParanoidP22301.
KOK05443.
OMAPHMLREL.
OrthoDBEOG7C2R33.
PhylomeDBP22301.
TreeFamTF333253.

Enzyme and pathway databases

SignaLinkP22301.

Gene expression databases

ArrayExpressP22301.
BgeeP22301.
CleanExHS_IL10.
GenevestigatorP22301.

Family and domain databases

Gene3D1.20.1250.10. 1 hit.
InterProIPR009079. 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]
PANTHERPTHR11585. PTHR11585. 1 hit.
PfamPF00726. IL10. 1 hit.
[Graphical view]
PRINTSPR01294. INTRLEUKIN10.
SMARTSM00188. IL10. 1 hit.
[Graphical view]
SUPFAMSSF47266. SSF47266. 1 hit.
PROSITEPS00520. INTERLEUKIN_10. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP22301.
GeneWikiInterleukin_10.
GenomeRNAi3586.
NextBio14011.
PROP22301.
SOURCESearch...

Entry information

Entry nameIL10_HUMAN
AccessionPrimary (citable) accession number: P22301
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: April 16, 2014
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM