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P22301

- IL10_HUMAN

UniProt

P22301 - IL10_HUMAN

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Protein

Interleukin-10

Gene

IL10

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. cytokine activity Source: BHF-UCL
  2. growth factor activity Source: UniProtKB
  3. interleukin-10 receptor binding Source: UniProtKB

GO - Biological processi

  1. B cell differentiation Source: UniProtKB
  2. B cell proliferation Source: UniProtKB
  3. branching involved in labyrinthine layer morphogenesis Source: Ensembl
  4. cell-cell signaling Source: UniProtKB
  5. cellular response to estradiol stimulus Source: Ensembl
  6. cellular response to lipopolysaccharide Source: BHF-UCL
  7. cytoplasmic sequestering of NF-kappaB Source: UniProtKB
  8. defense response to bacterium Source: Ensembl
  9. hemopoiesis Source: UniProtKB
  10. inflammatory response Source: BHF-UCL
  11. leukocyte chemotaxis Source: ProtInc
  12. negative regulation of apoptotic process Source: UniProtKB
  13. negative regulation of B cell proliferation Source: MGI
  14. negative regulation of chronic inflammatory response to antigenic stimulus Source: Ensembl
  15. negative regulation of cytokine secretion involved in immune response Source: BHF-UCL
  16. negative regulation of growth of symbiont in host Source: Ensembl
  17. negative regulation of interferon-alpha biosynthetic process Source: UniProtKB
  18. negative regulation of interferon-gamma production Source: Ensembl
  19. negative regulation of interleukin-12 production Source: Ensembl
  20. negative regulation of interleukin-6 production Source: BHF-UCL
  21. negative regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
  22. negative regulation of MHC class II biosynthetic process Source: UniProtKB
  23. negative regulation of myeloid dendritic cell activation Source: Ensembl
  24. negative regulation of nitric oxide biosynthetic process Source: Ensembl
  25. negative regulation of T cell proliferation Source: UniProtKB
  26. negative regulation of tumor necrosis factor biosynthetic process Source: Ensembl
  27. negative regulation of tumor necrosis factor production Source: Ensembl
  28. positive regulation of B cell apoptotic process Source: MGI
  29. positive regulation of cytokine secretion Source: BHF-UCL
  30. positive regulation of MHC class II biosynthetic process Source: Ensembl
  31. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  32. positive regulation of transcription, DNA-templated Source: BHF-UCL
  33. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  34. receptor biosynthetic process Source: BHF-UCL
  35. regulation of gene expression Source: MGI
  36. regulation of isotype switching Source: UniProtKB
  37. regulation of sensory perception of pain Source: Ensembl
  38. response to activity Source: Ensembl
  39. response to carbon monoxide Source: Ensembl
  40. response to drug Source: Ensembl
  41. response to glucocorticoid Source: BHF-UCL
  42. response to inactivity Source: Ensembl
  43. response to insulin Source: Ensembl
  44. response to molecule of bacterial origin Source: UniProtKB
  45. 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: Chromosome 1

Organism-specific databases

HGNCiHGNC:5962. IL10.

Subcellular locationi

GO - Cellular componenti

  1. 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.

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.
GenevestigatoriP22301.

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.

Polymorphism databases

DMDMi124292.

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.
UniGenei Hs.193717.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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 [» ]
ProteinModelPortali P22301.
SMRi P22301. Positions 24-178.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109800. 3 interactions.
DIPi DIP-3511N.
IntActi P22301. 2 interactions.
MINTi MINT-206740.
STRINGi 9606.ENSP00000412237.

PTM databases

PhosphoSitei P22301.

Polymorphism databases

DMDMi 124292.

Proteomic databases

PaxDbi P22301.
PRIDEi P22301.

Protocols and materials databases

DNASUi 3586.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000423557 ; ENSP00000412237 ; ENSG00000136634 .
GeneIDi 3586.
KEGGi hsa:3586.
UCSCi uc001hen.1. human.

Organism-specific databases

CTDi 3586.
GeneCardsi GC01M206940.
HGNCi HGNC:5962. IL10.
HPAi CAB013120.
MIMi 124092. gene.
614395. phenotype.
neXtProti NX_P22301.
Orphaneti 238569. Autosomal recessive early-onset inflammatory bowel disease.
117. Behcet disease.
536. Systemic lupus erythematosus.
PharmGKBi PA29778.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG43085.
HOGENOMi HOG000072692.
HOVERGENi HBG004110.
InParanoidi P22301.
KOi K05443.
OMAi PHMLREL.
OrthoDBi EOG7C2R33.
PhylomeDBi P22301.
TreeFami TF333253.

Enzyme and pathway databases

SignaLinki P22301.

Miscellaneous databases

EvolutionaryTracei P22301.
GeneWikii Interleukin_10.
GenomeRNAii 3586.
NextBioi 14011.
PROi P22301.
SOURCEi Search...

Gene expression databases

Bgeei P22301.
CleanExi HS_IL10.
ExpressionAtlasi P22301. baseline and differential.
Genevestigatori P22301.

Family and domain databases

Gene3Di 1.20.1250.10. 1 hit.
InterProi IPR009079. 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 ]
PANTHERi PTHR11585. PTHR11585. 1 hit.
Pfami PF00726. IL10. 1 hit.
[Graphical view ]
PRINTSi PR01294. INTRLEUKIN10.
SMARTi SM00188. IL10. 1 hit.
[Graphical view ]
SUPFAMi SSF47266. SSF47266. 1 hit.
PROSITEi PS00520. INTERLEUKIN_10. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: November 26, 2014
This is version 157 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