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Protein

Interleukin-36 gamma

Gene

IL36G

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

Functioni

Cytokine that binds to and signals through the IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells. Part of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; similar to the IL-1 system with which it shares the coreceptor IL1RAP. Seems to be involved in skin inflammatory response by acting on keratinocytes, dendritic cells and indirectly on T cells to drive tissue infiltration, cell maturation and cell proliferation. In cultured keratinocytes induces the expression of macrophage, T cell, and neutrophil chemokines, such as CCL3, CCL4, CCL5, CCL2, CCL17, CCL22, CL20, CCL5, CCL2, CCL17, CCL22, CXCL8, CCL20 and CXCL1; also stimulates its own expression and that of the prototypic cutaneous proinflammatory parameters TNF-alpha, S100A7/psoriasin and inducible NOS. May play a role in proinflammatory responses during particular neutrophilic airway inflammation: activates mitogen-activated protein kinases and NF-kappa B in primary lung fibroblasts, and stimulates the expression of IL-8 and CXCL3 and Th17 chemokine CCL20 in lung fibroblasts. May be involved in the innate immune response to fungal pathogens, such as Aspergillus fumigatus.6 Publications

GO - Molecular functioni

  1. cytokine activity Source: GO_Central
  2. interleukin-1 receptor binding Source: GO_Central

GO - Biological processi

  1. cell-cell signaling Source: ProtInc
  2. cytokine-mediated signaling pathway Source: GO_Central
  3. inflammatory response Source: UniProtKB-KW
  4. innate immune response Source: UniProtKB-KW
  5. negative regulation of myoblast differentiation Source: Ensembl
  6. negative regulation of myoblast fusion Source: Ensembl
  7. positive regulation of interleukin-6 production Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

SignaLinkiQ9NZH8.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-36 gamma
Alternative name(s):
IL-1-related protein 2
Short name:
IL-1RP2
Interleukin-1 epsilon
Short name:
IL-1 epsilon
Interleukin-1 family member 9
Short name:
IL-1F9
Interleukin-1 homolog 1
Short name:
IL-1H1
Gene namesi
Name:IL36G
Synonyms:IL1E, IL1F9, IL1H1, IL1RP2
ORF Names:UNQ2456/PRO5737
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:15741. IL36G.

Subcellular locationi

Secreted 1 Publication

GO - Cellular componenti

  1. extracellular space Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA38395.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei1 – 17171 PublicationPRO_0000430549Add
BLAST
Chaini18 – 169152Interleukin-36 gammaPRO_0000153648Add
BLAST

Post-translational modificationi

N-terminal truncation leads to a dramatic enhancement of its activity (>1000-fold).1 Publication

Proteomic databases

PaxDbiQ9NZH8.
PRIDEiQ9NZH8.

PTM databases

PhosphoSiteiQ9NZH8.

Expressioni

Tissue specificityi

Highly expressed in tissues containing epithelial cells: skin, lung, stomach and esophagus. Expressed in bronchial epithelial. In skin is expressed only in keratinocytes but not in fibroblasts, endothelial cells or melanocytes. Up-regulated in lesional psoriasis skin. Expressed in monocyte-derived dendritic cells and M1 macrophages.2 Publications

Inductioni

By TNF and by IFNG/IFN-gamma in keratinocytes. By Aspergillus fumigatus conidia in peripheral blood mnonocytes; involves CLEC7A and SYK.2 Publications

Gene expression databases

BgeeiQ9NZH8.
CleanExiHS_IL1F9.
ExpressionAtlasiQ9NZH8. baseline and differential.
GenevestigatoriQ9NZH8.

Interactioni

Protein-protein interaction databases

BioGridi121135. 1 interaction.

Structurei

Secondary structure

1
169
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi23 – 297Combined sources
Beta strandi33 – 386Combined sources
Beta strandi41 – 466Combined sources
Helixi47 – 493Combined sources
Beta strandi55 – 606Combined sources
Helixi64 – 663Combined sources
Helixi69 – 713Combined sources
Beta strandi73 – 808Combined sources
Turni81 – 833Combined sources
Beta strandi84 – 896Combined sources
Beta strandi91 – 944Combined sources
Beta strandi96 – 1016Combined sources
Helixi104 – 1096Combined sources
Beta strandi110 – 1123Combined sources
Helixi115 – 1173Combined sources
Beta strandi118 – 1247Combined sources
Beta strandi127 – 1359Combined sources
Beta strandi139 – 1424Combined sources
Beta strandi150 – 1534Combined sources
Beta strandi156 – 1605Combined sources
Beta strandi163 – 1675Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4IZEX-ray2.00A18-169[»]
4P0JX-ray2.30A/B154-160[»]
4P0KX-ray1.70A64-72[»]
A154-160[»]
4P0LX-ray1.55A64-72[»]
A154-160[»]
ProteinModelPortaliQ9NZH8.
SMRiQ9NZH8. Positions 21-169.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-1 family.Curated

Phylogenomic databases

eggNOGiNOG39912.
GeneTreeiENSGT00530000062899.
HOVERGENiHBG052100.
InParanoidiQ9NZH8.
KOiK05487.
OMAiVITCKYP.
PhylomeDBiQ9NZH8.
TreeFamiTF300203.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR000975. IL-1_fam.
IPR003297. IL-1RA/IL-36.
IPR027163. IL-36_alpha/gamma.
[Graphical view]
PANTHERiPTHR10078:SF14. PTHR10078:SF14. 1 hit.
PfamiPF00340. IL1. 1 hit.
[Graphical view]
PRINTSiPR00264. INTERLEUKIN1.
PR01360. INTRLEUKIN1X.
SUPFAMiSSF50353. SSF50353. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NZH8-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MRGTPGDADG GGRAVYQSMC KPITGTINDL NQQVWTLQGQ NLVAVPRSDS
60 70 80 90 100
VTPVTVAVIT CKYPEALEQG RGDPIYLGIQ NPEMCLYCEK VGEQPTLQLK
110 120 130 140 150
EQKIMDLYGQ PEPVKPFLFY RAKTGRTSTL ESVAFPDWFI ASSKRDQPII
160
LTSELGKSYN TAFELNIND
Length:169
Mass (Da):18,721
Last modified:October 1, 2000 - v1
Checksum:iF00A9243706F4154
GO
Isoform 2 (identifier: Q9NZH8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     19-54: MCKPITGTINDLNQQVWTLQGQNLVAVPRSDSVTPV → I

Note: No experimental confirmation available.

Show »
Length:134
Mass (Da):14,928
Checksum:iD5369C5AD44A9752
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti69 – 691Q → K.
Corresponds to variant rs6707930 [ dbSNP | Ensembl ].
VAR_024505

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei19 – 5436MCKPI…SVTPV → I in isoform 2. 1 PublicationVSP_013002Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF200492 mRNA. Translation: AAF69248.1.
AF206696 mRNA. Translation: AAG35670.1.
BN000002 Genomic DNA. Translation: CAD29874.1.
AY359111 mRNA. Translation: AAQ89469.1.
AY968311 Genomic DNA. Translation: AAX59035.1.
AC016724 Genomic DNA. Translation: AAY14987.1.
BC096721 mRNA. Translation: AAH96721.1.
BC098130 mRNA. Translation: AAH98130.1.
BC098155 mRNA. Translation: AAH98155.1.
BC098337 mRNA. Translation: AAH98337.1.
CCDSiCCDS2108.1. [Q9NZH8-1]
CCDS62992.1. [Q9NZH8-2]
RefSeqiNP_001265497.1. NM_001278568.1. [Q9NZH8-2]
NP_062564.1. NM_019618.3. [Q9NZH8-1]
UniGeneiHs.211238.

Genome annotation databases

EnsembliENST00000259205; ENSP00000259205; ENSG00000136688. [Q9NZH8-1]
ENST00000376489; ENSP00000365672; ENSG00000136688. [Q9NZH8-2]
GeneIDi56300.
KEGGihsa:56300.
UCSCiuc002tio.1. human. [Q9NZH8-1]
uc010fkr.1. human. [Q9NZH8-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Interleukin-1 entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF200492 mRNA. Translation: AAF69248.1.
AF206696 mRNA. Translation: AAG35670.1.
BN000002 Genomic DNA. Translation: CAD29874.1.
AY359111 mRNA. Translation: AAQ89469.1.
AY968311 Genomic DNA. Translation: AAX59035.1.
AC016724 Genomic DNA. Translation: AAY14987.1.
BC096721 mRNA. Translation: AAH96721.1.
BC098130 mRNA. Translation: AAH98130.1.
BC098155 mRNA. Translation: AAH98155.1.
BC098337 mRNA. Translation: AAH98337.1.
CCDSiCCDS2108.1. [Q9NZH8-1]
CCDS62992.1. [Q9NZH8-2]
RefSeqiNP_001265497.1. NM_001278568.1. [Q9NZH8-2]
NP_062564.1. NM_019618.3. [Q9NZH8-1]
UniGeneiHs.211238.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4IZEX-ray2.00A18-169[»]
4P0JX-ray2.30A/B154-160[»]
4P0KX-ray1.70A64-72[»]
A154-160[»]
4P0LX-ray1.55A64-72[»]
A154-160[»]
ProteinModelPortaliQ9NZH8.
SMRiQ9NZH8. Positions 21-169.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121135. 1 interaction.

PTM databases

PhosphoSiteiQ9NZH8.

Proteomic databases

PaxDbiQ9NZH8.
PRIDEiQ9NZH8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259205; ENSP00000259205; ENSG00000136688. [Q9NZH8-1]
ENST00000376489; ENSP00000365672; ENSG00000136688. [Q9NZH8-2]
GeneIDi56300.
KEGGihsa:56300.
UCSCiuc002tio.1. human. [Q9NZH8-1]
uc010fkr.1. human. [Q9NZH8-2]

Organism-specific databases

CTDi56300.
GeneCardsiGC02P113731.
HGNCiHGNC:15741. IL36G.
MIMi605542. gene.
neXtProtiNX_Q9NZH8.
PharmGKBiPA38395.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG39912.
GeneTreeiENSGT00530000062899.
HOVERGENiHBG052100.
InParanoidiQ9NZH8.
KOiK05487.
OMAiVITCKYP.
PhylomeDBiQ9NZH8.
TreeFamiTF300203.

Enzyme and pathway databases

SignaLinkiQ9NZH8.

Miscellaneous databases

GeneWikiiIL1F9.
GenomeRNAii56300.
NextBioi61963.
PROiQ9NZH8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NZH8.
CleanExiHS_IL1F9.
ExpressionAtlasiQ9NZH8. baseline and differential.
GenevestigatoriQ9NZH8.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR000975. IL-1_fam.
IPR003297. IL-1RA/IL-36.
IPR027163. IL-36_alpha/gamma.
[Graphical view]
PANTHERiPTHR10078:SF14. PTHR10078:SF14. 1 hit.
PfamiPF00340. IL1. 1 hit.
[Graphical view]
PRINTSiPR00264. INTERLEUKIN1.
PR01360. INTRLEUKIN1X.
SUPFAMiSSF50353. SSF50353. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification and initial characterization of four novel members of the interleukin-1 family."
    Kumar S., McDonnell P.C., Lehr R., Tierney L., Tzimas M.N., Griswold D.E., Capper E.A., Tal-Singer R., Wells G.I., Doyle M.L., Young P.R.
    J. Biol. Chem. 275:10308-10314(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION.
    Tissue: Keratinocyte.
  2. "Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2."
    Debets R., Timans J.C., Homey B., Zurawski S., Sana T.R., Lo S., Wagner J., Edwards G., Clifford T., Menon S., Bazan J.F., Kastelein R.A.
    J. Immunol. 167:1440-1446(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
    Tissue: Epithelium.
  3. "Identification and gene organization of three novel members of the IL-1 family on human chromosome 2."
    Busfield S.J., Comrack C.A., Yu G., Chickering T.W., Smutko J.S., Zhou H., Leiby K.R., Holmgren L.M., Gearing D.P., Pan Y.
    Genomics 66:213-216(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "A sequence-based map of the nine genes of the human interleukin-1 cluster."
    Nicklin M.J.H., Barton J.L., Nguyen M., Fitzgerald M.G., Duff W.G., Kornman K.
    Genomics 79:718-725(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  6. SeattleSNPs variation discovery resource
    Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  7. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2004) [PubMed] [Europe PMC] [Abstract]
    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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  9. "Regulation and function of the IL-1 family cytokine IL-1F9 in human bronchial epithelial cells."
    Chustz R.T., Nagarkar D.R., Poposki J.A., Favoreto S. Jr., Avila P.C., Schleimer R.P., Kato A.
    Am. J. Respir. Cell Mol. Biol. 45:145-153(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  10. "Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36alpha, IL-36beta, and IL-36gamma) or antagonist (IL-36Ra) activity."
    Towne J.E., Renshaw B.R., Douangpanya J., Lipsky B.P., Shen M., Gabel C.A., Sims J.E.
    J. Biol. Chem. 286:42594-42602(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PROCESSING.
  11. "IL-36gamma/IL-1F9, an innate T-bet target in myeloid cells."
    Bachmann M., Scheiermann P., Hardle L., Pfeilschifter J., Muhl H.
    J. Biol. Chem. 287:41684-41696(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  12. "The IL-36 receptor pathway regulates Aspergillus fumigatus-induced Th1 and Th17 responses."
    Gresnigt M.S., Roesler B., Jacobs C.W., Becker K.L., Joosten L.A., van der Meer J.W., Netea M.G., Dinarello C.A., van de Veerdonk F.L.
    Eur. J. Immunol. 43:416-426(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  13. "IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin."
    Foster A.M., Baliwag J., Chen C.S., Guzman A.M., Stoll S.W., Gudjonsson J.E., Ward N.L., Johnston A.
    J. Immunol. 192:6053-6061(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiIL36G_HUMAN
AccessioniPrimary (citable) accession number: Q9NZH8
Secondary accession number(s): Q56B91, Q6UVX7, Q7RTZ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: October 1, 2000
Last modified: March 4, 2015
This is version 116 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, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: 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.