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Protein

Interleukin-36 receptor antagonist protein

Gene

IL36RN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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-36RaIBD:
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.

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:rs387906914Ensembl.1
Natural variantiVAR_06664748R → W in PSORS14. 1 PublicationCorresponds to variant dbSNP:rs151325121Ensembl.1
Natural variantiVAR_066648113S → L in PSORS14. 1 PublicationCorresponds to variant dbSNP:rs144478519Ensembl.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:rs397514629Ensembl.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 ↔ 154HMP:

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiQ9UBH0.
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.
MINTiMINT-1194342.
STRINGi9606.ENSP00000259212.

Structurei

Secondary structure

1155
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 13ND:5
Beta strandi18 – 22ND:5
Beta strandi25 – 29ND:5
Beta strandi42 – 46ND:5
Helixi52 – 54ND:3
Beta strandi55 – 61ND:7
Turni62 – 65ND:4
Beta strandi66 – 69ND:4
Beta strandi72 – 75ND:4
Beta strandi79 – 82ND:4
Helixi85 – 89ND:5
Helixi96 – 98ND:3
Beta strandi99 – 102ND:4
Beta strandi109 – 116ND:8
Beta strandi120 – 123ND:4
Beta strandi132 – 135ND:4
Beta strandi149 – 153ND:5

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.IKR:

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:rs387906914Ensembl.1
Natural variantiVAR_02323947N → S1 PublicationCorresponds to variant dbSNP:rs28938777Ensembl.1
Natural variantiVAR_06664748R → W in PSORS14. 1 PublicationCorresponds to variant dbSNP:rs151325121Ensembl.1
Natural variantiVAR_066648113S → L in PSORS14. 1 PublicationCorresponds to variant dbSNP:rs144478519Ensembl.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:rs397514629Ensembl.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: November 22, 2017
This is version 152 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

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