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Protein

Interleukin-36 receptor antagonist protein

Gene

IL36RN

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

Functioni

Inhibits the activity of interleukin-36 (IL36A,IL36B and IL36G) by binding to receptor IL1RL2 and preventing its association with the coreceptor IL1RAP for signaling. 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. Proposed to play a role in skin inflammation. May be involved in the innate immune response to fungal pathogens, such as Aspergillus fumigatus. May activate an anti-inflammatory signaling pathway by recruiting SIGIRR.3 Publications

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • interleukin-1 receptor antagonist activity Source: ProtInc
  • interleukin-1 receptor binding Source: GO_Central

GO - Biological processi

  • antifungal humoral response Source: UniProtKB
  • cytokine-mediated signaling pathway Source: Reactome
  • inflammatory response Source: InterPro
  • innate immune response Source: UniProtKB-KW
  • negative regulation of cytokine-mediated signaling pathway Source: UniProtKB
  • negative regulation of interferon-gamma secretion Source: UniProtKB
  • negative regulation of interleukin-17 production Source: UniProtKB
  • negative regulation of interleukin-6 production Source: Ensembl

Keywordsi

Molecular functionCytokine
Biological processImmunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-9014826 Interleukin-36 pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-36 receptor antagonist protein
Short name:
IL-36Ra1 Publication
Alternative name(s):
FIL1 delta
IL-1-related protein 3
Short name:
IL-1RP3
Interleukin-1 HY1
Short name:
IL-1HY1
Interleukin-1 delta
Short name:
IL-1 delta
Interleukin-1 family member 5
Short name:
IL-1F5
Interleukin-1 receptor antagonist homolog 1
Short name:
IL-1ra homolog 1
Interleukin-1-like protein 1
Short name:
IL-1L1
Gene namesi
Name:IL36RN
Synonyms:FIL1D, IL1F5, IL1HY1, IL1L1, IL1RP3
ORF Names:UNQ1896/PRO4342
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000136695.14
HGNCiHGNC:15561 IL36RN
MIMi605507 gene
neXtProtiNX_Q9UBH0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Psoriasis 14, pustular (PSORS14)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA life-threatening disease defined by repeated flares of sudden onset consisting of diffuse erythematous skin eruption characterized by rapid coverage with pustules, high-grade fever, asthenia, marked leukocytosis, and elevated serum levels of C-reactive protein.
See also OMIM:614204
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06664627L → P in PSORS14; expression of the protein is severely impaired compared to wild-type; the mutant protein is substantially less able to inhibit IL1RL2 signaling than wild-type. 1 PublicationCorresponds to variant dbSNP:rs387906914EnsemblClinVar.1
Natural variantiVAR_06664748R → W in PSORS14. 1 PublicationCorresponds to variant dbSNP:rs151325121EnsemblClinVar.1
Natural variantiVAR_066648113S → L in PSORS14. 1 PublicationCorresponds to variant dbSNP:rs144478519EnsemblClinVar.1
Natural variantiVAR_068972123T → R in PSORS14; shows impaired expression of the mutant protein which fails to antagonize the IL-36 signaling pathway. 1 PublicationCorresponds to variant dbSNP:rs397514629EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi26525
MalaCardsiIL36RN
MIMi614204 phenotype
OpenTargetsiENSG00000136695
Orphaneti163931 Acrodermatitis continua suppurativa of Hallopeau
404546 DITRA
247353 Generalized pustular psoriasis
163927 Pustulosis palmaris et plantaris
PharmGKBiPA38388

Polymorphism and mutation databases

BioMutaiIL36RN
DMDMi25008600

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001536422 – 155Interleukin-36 receptor antagonist proteinAdd BLAST154

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi8 ↔ 154By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiQ9UBH0
PeptideAtlasiQ9UBH0
PRIDEiQ9UBH0

PTM databases

iPTMnetiQ9UBH0
PhosphoSitePlusiQ9UBH0

Expressioni

Tissue specificityi

Predominantly expressed in skin keratinocytes but not in fibroblasts, endothelial cells or melanocytes. Detected also in the spleen, brain leukocyte and macrophage cell types. Increased in lesional psoriasis skin.1 Publication

Inductioni

By phorbol ester (PMA) and bacterial lipopolysaccharides (LPS) treatment in macrophage cell line. By Aspergillus fumigatus conidia in peripheral blood mnonocytes.1 Publication

Gene expression databases

BgeeiENSG00000136695
CleanExiHS_IL1F5
ExpressionAtlasiQ9UBH0 baseline and differential
GenevisibleiQ9UBH0 HS

Organism-specific databases

HPAiHPA034542

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • interleukin-1 receptor antagonist activity Source: ProtInc
  • interleukin-1 receptor binding Source: GO_Central

Protein-protein interaction databases

BioGridi117728, 16 interactors
IntActiQ9UBH0, 14 interactors
MINTiQ9UBH0
STRINGi9606.ENSP00000259212

Structurei

Secondary structure

1155
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 13Combined sources5
Beta strandi18 – 22Combined sources5
Beta strandi25 – 29Combined sources5
Beta strandi42 – 46Combined sources5
Helixi52 – 54Combined sources3
Beta strandi55 – 61Combined sources7
Turni62 – 65Combined sources4
Beta strandi66 – 69Combined sources4
Beta strandi72 – 75Combined sources4
Beta strandi79 – 82Combined sources4
Helixi85 – 89Combined sources5
Helixi96 – 98Combined sources3
Beta strandi99 – 102Combined sources4
Beta strandi109 – 116Combined sources8
Beta strandi120 – 123Combined sources4
Beta strandi132 – 135Combined sources4
Beta strandi149 – 153Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4P0JX-ray2.30A/B2-135[»]
A/B147-155[»]
4P0KX-ray1.70A2-49[»]
A55-135[»]
A147-155[»]
4P0LX-ray1.55A2-49[»]
A55-135[»]
A147-155[»]
ProteinModelPortaliQ9UBH0
SMRiQ9UBH0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-1 family.Curated

Phylogenomic databases

eggNOGiENOG410IZIW Eukaryota
ENOG41116AA LUCA
GeneTreeiENSGT00900000141028
HOVERGENiHBG052099
InParanoidiQ9UBH0
KOiK05483
OMAiALCFRMK
OrthoDBiEOG091G0PWA
PhylomeDBiQ9UBH0
TreeFamiTF300203

Family and domain databases

InterProiView protein in InterPro
IPR020877 IL-1_CS
IPR000975 IL-1_fam
IPR003297 IL-1RA/IL-36
IPR027171 IL-36RA
IPR008996 IL1/FGF
PANTHERiPTHR45145 PTHR45145, 1 hit
PfamiView protein in Pfam
PF00340 IL1, 1 hit
PRINTSiPR00264 INTERLEUKIN1
PR01360 INTRLEUKIN1X
SUPFAMiSSF50353 SSF50353, 1 hit
PROSITEiView protein in PROSITE
PS00253 INTERLEUKIN_1, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q9UBH0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVLSGALCFR MKDSALKVLY LHNNQLLAGG LHAGKVIKGE EISVVPNRWL
60 70 80 90 100
DASLSPVILG VQGGSQCLSC GVGQEPTLTL EPVNIMELYL GAKESKSFTF
110 120 130 140 150
YRRDMGLTSS FESAAYPGWF LCTVPEADQP VRLTQLPENG GWNAPITDFY

FQQCD
Length:155
Mass (Da):16,962
Last modified:May 1, 2000 - v1
Checksum:iB96DB5EFA2612E25
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06664627L → P in PSORS14; expression of the protein is severely impaired compared to wild-type; the mutant protein is substantially less able to inhibit IL1RL2 signaling than wild-type. 1 PublicationCorresponds to variant dbSNP:rs387906914EnsemblClinVar.1
Natural variantiVAR_02323947N → S1 PublicationCorresponds to variant dbSNP:rs28938777Ensembl.1
Natural variantiVAR_06664748R → W in PSORS14. 1 PublicationCorresponds to variant dbSNP:rs151325121EnsemblClinVar.1
Natural variantiVAR_066648113S → L in PSORS14. 1 PublicationCorresponds to variant dbSNP:rs144478519EnsemblClinVar.1
Natural variantiVAR_068972123T → R in PSORS14; shows impaired expression of the mutant protein which fails to antagonize the IL-36 signaling pathway. 1 PublicationCorresponds to variant dbSNP:rs397514629EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF201830 mRNA Translation: AAF25210.1
AF186094 mRNA Translation: AAF02757.1
AJ242737 mRNA Translation: CAB59822.1
AJ242738 mRNA Translation: CAB59823.1
AJ271338 Genomic DNA Translation: CAB67704.1
AF216693 Genomic DNA Translation: AAF76981.1
AF230377 mRNA Translation: AAF91274.1
BN000002 Genomic DNA Translation: CAD29877.1
AY359117 mRNA Translation: AAQ89475.1
AK290249 mRNA Translation: BAF82938.1
AY972853 Genomic DNA Translation: AAX59031.1
AC016724 Genomic DNA Translation: AAY14990.1
CH471217 Genomic DNA Translation: EAW73617.1
BC024747 mRNA Translation: AAH24747.1
CCDSiCCDS2111.1
PIRiJC7104
RefSeqiNP_036407.1, NM_012275.2
NP_775262.1, NM_173170.1
UniGeneiHs.516301

Genome annotation databases

EnsembliENST00000346807; ENSP00000259212; ENSG00000136695
ENST00000393200; ENSP00000376896; ENSG00000136695
GeneIDi26525
KEGGihsa:26525
UCSCiuc002tis.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiI36RA_HUMAN
AccessioniPrimary (citable) accession number: Q9UBH0
Secondary accession number(s): A8K2I4, Q56AT9, Q7RTZ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2002
Last sequence update: May 1, 2000
Last modified: May 23, 2018
This is version 156 of the entry and version 1 of the sequence. See 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

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