Q14116 (IL18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Interleukin-18
Short name=IL-18

Alternative name(s):
Iboctadekin
Interferon gamma-inducing factor
Short name=IFN-gamma-inducing factor
Interleukin-1 gamma
Short name=IL-1 gamma

Gene names

Name:	IL18
Synonyms:	IGIF, IL1F4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	193 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	Augments natural killer cell activity in spleen cells and stimulates interferon gamma production in T-helper type I cells.
Subcellular location	Secreted.
Post-translational modification	The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield the active form.
Sequence similarities	Belongs to the IL-1 family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Molecular function	Cytokine
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from mutant phenotype PubMed 21147091. Source: UniProtKB T-helper 1 type immune response Inferred from direct assay PubMed 8766574. Source: UniProtKB angiogenesis Inferred from direct assay PubMed 11466388. Source: UniProtKB cell-cell signaling Traceable author statement PubMed 9792649. Source: ProtInc cellular response to cAMP Inferred from electronic annotation. Source: Compara cellular response to hydrogen peroxide Inferred from electronic annotation. Source: Compara cellular response to interferon-gamma Inferred from electronic annotation. Source: Compara cellular response to mechanical stimulus Inferred from electronic annotation. Source: Compara cellular response to organic cyclic compound Inferred from direct assay PubMed 21147091. Source: UniProtKB cellular response to parathyroid hormone stimulus Inferred from electronic annotation. Source: Compara cellular response to peptide hormone stimulus Inferred from electronic annotation. Source: Compara cellular response to tumor necrosis factor Inferred from electronic annotation. Source: Compara chemokine biosynthetic process Traceable author statement PubMed 11598150. Source: UniProtKB detection of mechanical stimulus involved in sensory perception of pain Inferred from electronic annotation. Source: Compara digestive tract morphogenesis Inferred from electronic annotation. Source: Compara granulocyte macrophage colony-stimulating factor biosynthetic process Traceable author statement PubMed 10653850. Source: UniProtKB inflammatory response Inferred from direct assay PubMed 21147091. Source: UniProtKB interferon-gamma biosynthetic process Traceable author statement PubMed 10227975. Source: UniProtKB interleukin-13 biosynthetic process Traceable author statement PubMed 10227975. Source: UniProtKB interleukin-2 biosynthetic process Traceable author statement PubMed 10653850. Source: UniProtKB lipopolysaccharide-mediated signaling pathway Inferred from direct assay PubMed 21147091. Source: UniProtKB lung development Inferred from electronic annotation. Source: Compara osteoblast differentiation Inferred from electronic annotation. Source: Compara positive regulation of NK T cell proliferation Inferred from direct assay PubMed 19088061. Source: BHF-UCL positive regulation of activated T cell proliferation Inferred from direct assay PubMed 10000000PubMed 8766574. Source: UniProtKB positive regulation of blood vessel remodeling Inferred from electronic annotation. Source: Compara positive regulation of chemokine production Inferred from electronic annotation. Source: Compara positive regulation of collagen biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of gene expression Inferred from electronic annotation. Source: Compara positive regulation of granulocyte macrophage colony-stimulating factor production Inferred from direct assay PubMed 20027291. Source: BHF-UCL positive regulation of inflammatory response Inferred by curator PubMed 16482511. Source: BHF-UCL positive regulation of interferon-gamma production Inferred from direct assay PubMed 19088061PubMed 20027291. Source: BHF-UCL positive regulation of interleukin-1 beta production Inferred from electronic annotation. Source: Compara positive regulation of interleukin-17 production Inferred from direct assay PubMed 16482511. Source: BHF-UCL positive regulation of interleukin-8 production Inferred from electronic annotation. Source: Compara positive regulation of male germ cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of natural killer cell proliferation Inferred from direct assay PubMed 19088061. Source: BHF-UCL positive regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of superoxide anion generation Inferred from electronic annotation. Source: Compara positive regulation of tissue remodeling Inferred by curator PubMed 16482511. Source: BHF-UCL positive regulation of tumor necrosis factor production Inferred from electronic annotation. Source: Compara positive regulation of vascular permeability Inferred from electronic annotation. Source: Compara regulation of cell adhesion Inferred from direct assay PubMed 11477102. Source: UniProtKB response to cold Inferred from electronic annotation. Source: Compara response to hyperoxia Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to radiation Inferred from electronic annotation. Source: Compara sleep Inferred from sequence or structural similarity PubMed 11506998. Source: UniProtKB type 2 immune response Traceable author statement PubMed 11905033. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome extracellular region Traceable author statement PubMed 11598150. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	cytokine activity Traceable author statement PubMed 11598150. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q14116-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q14116-2)

Also known as: Delta3pro-IL-18;

The sequence of this isoform differs from the canonical sequence as follows:
     27-30: Missing.

Note: Expressed in ovarian carcinoma but undetectable in normal ovarian epithelial cells. Resistant to proteolytic activation by caspase-1 and -4.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – 36

36

By similarity

PRO_0000015343

Chain

37 – 193

157

Interleukin-18

PRO_0000015344

Natural variations

Alternative sequence

27 – 30

4

Missing in isoform 2.

VSP_044934

Experimental info

Sequence conflict

66

1

F → L in AAC27787. Ref.3

Sequence conflict

86

1

S → R in AAC27787. Ref.3

Sequence conflict

191

1

N → S in AAC27787. Ref.3

Secondary structure

1

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193

Helix Strand Turn

Details...

Beta strand

42 – 49

8

Beta strand

55 – 58

4

Beta strand

64 – 67

4

Helix

71 – 76

6

Turn

77 – 81

5

Beta strand

83 – 91

9

Turn

92 – 94

3

Beta strand

95 – 111

17

Helix

113 – 115

3

Beta strand

118 – 121

4

Beta strand

126 – 131

6

Beta strand

137 – 142

6

Beta strand

145 – 156

12

Beta strand

159 – 166

8

Beta strand

169 – 176

8

Helix

183 – 185

3

Beta strand

187 – 191

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 323C62C203788D55	FASTA	193	22,326
	10 20 30 40 50 60 MAAEPVEDNC INFVAMKFID NTLYFIAEDD ENLESDYFGK LESKLSVIRN LNDQVLFIDQ 70 80 90 100 110 120 GNRPLFEDMT DSDCRDNAPR TIFIISMYKD SQPRGMAVTI SVKCEKISTL SCENKIISFK 130 140 150 160 170 180 EMNPPDNIKD TKSDIIFFQR SVPGHDNKMQ FESSSYEGYF LACEKERDLF KLILKKEDEL 190 GDRSIMFTVQ NED
	Isoform 2 (Delta3pro-IL-18) [UniParc]. Checksum: A8BA275CF713A4B6	FASTA	189	21,896
	10 20 30 40 50 60 MAAEPVEDNC INFVAMKFID NTLYFIENLE SDYFGKLESK LSVIRNLNDQ VLFIDQGNRP 70 80 90 100 110 120 LFEDMTDSDC RDNAPRTIFI ISMYKDSQPR GMAVTISVKC EKISTLSCEN KIISFKEMNP 130 140 150 160 170 180 PDNIKDTKSD IIFFQRSVPG HDNKMQFESS SYEGYFLACE KERDLFKLIL KKEDELGDRS IMFTVQNED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the cDNA for human IFN-gamma-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein." Ushio S., Namba M., Okura T., Hattori K., Nukada Y., Akita K., Tanabe F., Konishi K., Micallef M., Fujii M., Torigoe K., Tanimoto T., Fukuda S., Ikeda M., Okamura H., Kurimoto M. J. Immunol. 156:4274-4279(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[2]	"A novel isoform of pro-interleukin-18 expressed in ovarian tumors is resistant to caspase-1 and -4 processing." Gaggero A., De Ambrosis A., Mezzanzanica D., Piazza T., Rubartelli A., Figini M., Canevari S., Ferrini S. Oncogene 23:7552-7560(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEOLYTIC PROCESSING, ALTERNATIVE SPLICING.
[3]	"Cloning and sequencing of the cDNA for precursor hIL-18." Yong D., Guixin D., Lihua H., Haitao W. Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Cloning of human interleukin 18 cDNA." Liu J., Peng X., Yuan J., Qiang B. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Urinary bladder.
[9]	Conti B., Kim S.J., Tinti C., Chun H.S., Joh T.H. Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-193 (ISOFORM 1). Tissue: Peripheral blood.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

Wikipedia

Interleukin-1 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D49950 mRNA. Translation: BAA08706.1.
AY266351 mRNA. Translation: AAP92112.1.
AF077611 mRNA. Translation: AAC27787.1.
AY044641 mRNA. Translation: AAK95950.1.
CR541973 mRNA. Translation: CAG46771.1.
CR542001 mRNA. Translation: CAG46798.1.
AP002007 Genomic DNA. No translation available.
AP002884 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67184.1.
BC007007 mRNA. Translation: AAH07007.1.
BC007461 mRNA. Translation: AAH07461.1.
U90434 mRNA. Translation: AAB50010.1.

IPI

IPI00290198.
IPI00980067.

RefSeq

NP_001230140.1. NM_001243211.1.
NP_001553.1. NM_001562.3.

UniGene

Hs.83077.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J0S	NMR	-	A	37-193	[»]
2VXT	X-ray	1.49	I	37-193	[»]
3F62	X-ray	2.00	B	37-193	[»]
4EEE	X-ray	2.71	B/D	37-193	[»]
4EKX	X-ray	1.75	B/D	37-193	[»]

ProteinModelPortal

Q14116.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-3785N.

IntAct

Q14116. 1 interaction.

STRING

9606.ENSP00000280357.

PTM databases

PhosphoSite

Q14116.

Polymorphism databases

DMDM

3219817.

2D gel databases

OGP

Q14116.

Proteomic databases

PaxDb

Q14116.

PRIDE

Q14116.

Protocols and materials databases

DNASU

3606.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000280357; ENSP00000280357; ENSG00000150782.
ENST00000524595; ENSP00000434561; ENSG00000150782.
ENST00000528832; ENSP00000434161; ENSG00000150782.

GeneID

3606.

KEGG

hsa:3606.

UCSC

uc001pna.2. human.

Organism-specific databases

CTD

3606.

GeneCards

GC11M112013.

HGNC

HGNC:5986. IL18.

HPA

CAB007772.
CAB027385.
HPA003980.

MIM

600953. gene.

neXtProt

NX_Q14116.

PharmGKB

PA29802.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG77229.

HOGENOM

HOG000048723.

HOVERGEN

HBG000388.

InParanoid

Q14116.

KO

K05482.

OMA

VPGHDDK.

OrthoDB

EOG4B8JFJ.

Enzyme and pathway databases

Pathway_Interaction_DB

anthraxpathway. Cellular roles of Anthrax toxin.
il12_stat4pathway. IL12 signaling mediated by STAT4.
il12_2pathway. IL12-mediated signaling events.
il23pathway. IL23-mediated signaling events.
il27pathway. IL27-mediated signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q14116.

Bgee

Q14116.

CleanEx

HS_IL18.

Genevestigator

Q14116.

GermOnline

ENSG00000150782. Homo sapiens.

Family and domain databases

InterPro

IPR008996. Cytokine_IL1-like.
IPR000975. Interleukin_1.
IPR015529. Interleukin_18.
[Graphical view]

PANTHER

PTHR11326. PTHR11326. 1 hit.

Pfam

PF00340. IL1. 1 hit.
[Graphical view]

PIRSF

PIRSF015162. Interleukin_18. 1 hit.

PRINTS

PR01933. INTRLEUKIN18.

SMART

SM00125. IL1. 1 hit.
[Graphical view]

SUPFAM

SSF50353. Cytok_IL1_like. 1 hit.

ProtoNet

Search...

Other

ChEMBL

CHEMBL1741305.

EvolutionaryTrace

Q14116.

GenomeRNAi

3606.

NextBio

14093.

PMAP-CutDB

Q14116.

SOURCE

Search...

Entry information

Entry name

IL18_HUMAN

Accession

Primary (citable) accession number: Q14116
Secondary accession number(s): O75599, Q6FGY3, Q6WWJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 123 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.