P22301 (IL10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-10
Short name=IL-10

Alternative name(s):
Cytokine synthesis inhibitory factor
Short name=CSIF

Gene names

Name:

IL10

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	178 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Sequence similarities	Belongs to the IL-10 family.

Ontologies

Keywords
Cellular component	Secreted
Disease	Disease mutation
Domain	Signal
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	B cell differentiation Non-traceable author statement. Source: UniProtKB B cell proliferation Non-traceable author statement. Source: UniProtKB anti-apoptosis Non-traceable author statement. Source: UniProtKB cell-cell signaling Inferred by curator Ref.1. Source: UniProtKB cytoplasmic sequestering of NF-kappaB Non-traceable author statement. Source: UniProtKB inflammatory response Inferred from direct assay. Source: BHF-UCL leukocyte chemotaxis Traceable author statement. Source: ProtInc negative regulation of B cell proliferation Inferred from direct assay. Source: MGI negative regulation of MHC class II biosynthetic process Traceable author statement. Source: UniProtKB negative regulation of T cell proliferation Non-traceable author statement. Source: UniProtKB negative regulation of cytokine secretion involved in immune response Inferred from direct assay. Source: BHF-UCL negative regulation of interferon-alpha biosynthetic process Non-traceable author statement. Source: UniProtKB negative regulation of interleukin-6 production Inferred from direct assay. Source: BHF-UCL negative regulation of membrane protein ectodomain proteolysis Inferred from direct assay. Source: BHF-UCL positive regulation of B cell apoptosis Inferred from direct assay. Source: MGI positive regulation of cytokine secretion Inferred from direct assay. Source: BHF-UCL positive regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from direct assay. Source: BHF-UCL receptor biosynthetic process Inferred from direct assay. Source: BHF-UCL regulation of isotype switching Non-traceable author statement. Source: UniProtKB response to glucocorticoid stimulus Inferred from direct assay. Source: BHF-UCL type 2 immune response Traceable author statement. Source: UniProtKB
Cellular component	extracellular space Inferred from direct assay. Source: BHF-UCL
Molecular function	cytokine activity Non-traceable author statement. Source: BHF-UCL growth factor activity Non-traceable author statement. Source: UniProtKB interleukin-10 receptor binding Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Ref.6

Chain

19 – 178

160

Interleukin-10

PRO_0000015360

Amino acid modifications

Glycosylation

134

1

N-linked (GlcNAc...) Potential

Disulfide bond

30 ↔ 126

Ref.7

Disulfide bond

80 ↔ 132

Ref.7

Natural variations

Natural variant

15

1

G → R in a family affected by Crohn disease; decreases secretion thereby reducing the anti-inflammatory effect. Ref.13

VAR_015883

Secondary structure

1

.

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.

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178

Helix Strand Turn

Details...

Turn

29 – 36

8

Helix

37 – 58

22

Helix

68 – 75

8

Helix

79 – 92

14

Helix

95 – 98

4

Helix

103 – 105

3

Helix

106 – 125

20

Helix

131 – 133

3

Helix

137 – 149

13

Helix

151 – 159

9

Helix

161 – 176

16

Sequences

	Sequence		Length	Mass (Da)
	P22301 [UniParc]. Last modified August 1, 1991. Version 1. Checksum: 6825E9FA4337CDE4	FASTA	178	20,517
	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

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: 1847510] [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: 9405662] [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: 15340161] [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: 8364028] [Abstract] Cited for: DISULFIDE BONDS.
[8]	"Crystal structure of interleukin 10 reveals an interferon gamma-like fold." Walter M.R., Nagabhushan T.L. Biochemistry 34:12118-12125(1995) [PubMed: 7547951] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[9]	"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: 8590020] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[10]	"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: 8897595] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
[11]	"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: 11485736] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 19-178 IN COMPLEX WITH IL10R1.
[12]	"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: 15837194] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 19-178 IN COMPLEX WITH IL10R1.
[13]	"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: 12825869] [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.

IPI

IPI00026102.

PIR

A38580.

RefSeq

NP_000563.1. NM_000572.2.

UniGene

Hs.193717.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P22301.

SMR

P22301. Positions 24-178.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-3511N.

IntAct

P22301. 1 interaction.

MINT

MINT-206740.

STRING

P22301.

Polymorphism databases

DMDM

124292.

Proteomic databases

PRIDE

P22301.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000423557; ENSP00000412237; ENSG00000136634.

GeneID

3586.

KEGG

hsa:3586.

UCSC

uc001hen.1. human.

Organism-specific databases

CTD

3586.

GeneCards

GC01M206940.

H-InvDB

HIX0023529.

HGNC

HGNC:5962. IL10.

HPA

CAB013120.

MIM

124092. gene.

neXtProt

NX_P22301.

Orphanet

117. Behcet disease.
206. Crohn disease.

PharmGKB

PA29778.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19191.

HOGENOM

HBG279172.

HOVERGEN

HBG004110.

InParanoid

P22301.

OMA

KGYLGCQ.

OrthoDB

EOG4F1X4G.

PhylomeDB

P22301.

Enzyme and pathway databases

Pathway_Interaction_DB

il4_2pathway. IL4-mediated signaling events.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.

Gene expression databases

ArrayExpress

P22301.

Bgee

P22301.

CleanEx

HS_IL10.

Genevestigator

P22301.

GermOnline

ENSG00000136634. Homo sapiens.

Family and domain databases

InterPro

IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR020443. Interleukin-10/19/20/24.
IPR020423. Interleukin-10_CS.
IPR000098. Interleukin_10.
[Graphical view]

Gene3D

G3DSA:1.20.1250.10. 4_helix_cytokine_core. 1 hit.

KO

K05443.

PANTHER

PTHR11585. Interleukin_10. 1 hit.

Pfam

PF00726. IL10. 1 hit.
[Graphical view]

PRINTS

PR01294. INTRLEUKIN10.

SMART

SM00188. IL10. 1 hit.
[Graphical view]

SUPFAM

SSF47266. 4_helix_cytokine. 1 hit.

PROSITE

PS00520. INTERLEUKIN_10. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

14011.

SOURCE

Search...

Entry information

Entry name

IL10_HUMAN

Accession

Primary (citable) accession number: P22301

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1991
Last modified:	January 25, 2012
This is version 130 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.