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Protein

Interleukin-1 receptor antagonist protein

Gene

IL1RN

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

Functioni

Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unsure.1 Publication

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • interleukin-1, Type II receptor binding Source: BHF-UCL
  • interleukin-1, Type I receptor binding Source: BHF-UCL
  • interleukin-1 receptor antagonist activity Source: BHF-UCL
  • interleukin-1 receptor binding Source: BHF-UCL
  • interleukin-1 Type II receptor antagonist activity Source: BHF-UCL
  • interleukin-1 Type I receptor antagonist activity Source: BHF-UCL

GO - Biological processi

  • acute-phase response Source: BHF-UCL
  • cytokine-mediated signaling pathway Source: Reactome
  • fever generation Source: GO_Central
  • immune response Source: UniProtKB
  • insulin secretion Source: Ensembl
  • interleukin-1-mediated signaling pathway Source: Reactome
  • lipid metabolic process Source: Ensembl
  • negative regulation of heterotypic cell-cell adhesion Source: BHF-UCL
  • negative regulation of interleukin-1-mediated signaling pathway Source: BHF-UCL
  • response to glucocorticoid Source: BHF-UCL

Enzyme and pathway databases

ReactomeiR-HSA-6783783 Interleukin-10 signaling
R-HSA-9020702 Interleukin-1 signaling
SIGNORiP18510

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-1 receptor antagonist protein
Short name:
IL-1RN
Short name:
IL-1ra
Short name:
IRAP
Alternative name(s):
ICIL-1RA
IL1 inhibitor
INN: Anakinra
Gene namesi
Name:IL1RN
Synonyms:IL1F3, IL1RA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000136689.18
HGNCiHGNC:6000 IL1RN
MIMi147679 gene
neXtProtiNX_P18510

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

Cytoplasm, Secreted

Pathology & Biotechi

Involvement in diseasei

Microvascular complications of diabetes 4 (MVCD4)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionPathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
See also OMIM:612628
Interleukin 1 receptor antagonist deficiency (DIRA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare autoinflammatory disease of skin and bone resulting in sterile multifocal osteomyelitis, periostitis, and pustulosis from birth. The term autoinflammatory disease describes a group of disorders characterized by attacks of seemingly unprovoked inflammation without significant levels of autoantibodies and autoreactive T-cells.
See also OMIM:612852

Pharmaceutical usei

Available under the name Kineret (Amgen). Used for the reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis.

Organism-specific databases

DisGeNETi3557
MalaCardsiIL1RN
MIMi612628 phenotype
612852 phenotype
OpenTargetsiENSG00000136689
Orphaneti210115 Sterile multifocal osteomyelitis with periostitis and pustulosis
PharmGKBiPA29816

Protein family/group databases

Allergomei11858 Hom s Anakinra

Chemistry databases

DrugBankiDB06372 Rilonacept

Polymorphism and mutation databases

BioMutaiIL1RN
DMDMi124312

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 252 PublicationsAdd BLAST25
ChainiPRO_000001532826 – 177Interleukin-1 receptor antagonist proteinAdd BLAST152

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi91 ↔ 141
Glycosylationi109N-linked (GlcNAc...) asparagine2 Publications1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP18510
PaxDbiP18510
PeptideAtlasiP18510
PRIDEiP18510
ProteomicsDBi53572
53573 [P18510-2]
53574 [P18510-3]
53575 [P18510-4]

PTM databases

iPTMnetiP18510
PhosphoSitePlusiP18510

Expressioni

Tissue specificityi

The intracellular form of IL1RN is predominantly expressed in epithelial cells.

Gene expression databases

BgeeiENSG00000136689
CleanExiHS_IL1RN
ExpressionAtlasiP18510 baseline and differential
GenevisibleiP18510 HS

Organism-specific databases

HPAiCAB009633
HPA001482

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF2IPQ9NYB02EBI-1026330,EBI-750109

GO - Molecular functioni

  • cytokine activity Source: GO_Central
  • interleukin-1, Type II receptor binding Source: BHF-UCL
  • interleukin-1, Type I receptor binding Source: BHF-UCL
  • interleukin-1 receptor antagonist activity Source: BHF-UCL
  • interleukin-1 receptor binding Source: BHF-UCL
  • interleukin-1 Type II receptor antagonist activity Source: BHF-UCL
  • interleukin-1 Type I receptor antagonist activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi109772, 12 interactors
IntActiP18510, 3 interactors
STRINGi9606.ENSP00000259206

Structurei

Secondary structure

1177
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi36 – 42Combined sources7
Turni43 – 45Combined sources3
Beta strandi47 – 51Combined sources5
Beta strandi54 – 58Combined sources5
Helixi62 – 67Combined sources6
Beta strandi71 – 76Combined sources6
Turni77 – 79Combined sources3
Beta strandi80 – 85Combined sources6
Turni86 – 89Combined sources4
Beta strandi90 – 97Combined sources8
Beta strandi100 – 106Combined sources7
Helixi110 – 112Combined sources3
Helixi118 – 123Combined sources6
Beta strandi124 – 130Combined sources7
Beta strandi133 – 141Combined sources9
Beta strandi145 – 151Combined sources7
Beta strandi157 – 160Combined sources4
Beta strandi162 – 168Combined sources7
Beta strandi171 – 175Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ILRX-ray2.101/226-177[»]
1ILTX-ray2.00A/B26-177[»]
1IRAX-ray2.70X26-177[»]
1IRPNMR-A26-177[»]
1ITNmodel-A31-177[»]
2IRTX-ray3.20A/B26-177[»]
ProteinModelPortaliP18510
SMRiP18510
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP18510

Family & Domainsi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IZQ4 Eukaryota
ENOG41119SQ LUCA
GeneTreeiENSGT00900000141028
HOGENOMiHOG000231506
HOVERGENiHBG052099
InParanoidiP18510
KOiK05481
OMAiIHGGKLC
OrthoDBiEOG091G0PWA
PhylomeDBiP18510
TreeFamiTF300203

Family and domain databases

InterProiView protein in InterPro
IPR020877 IL-1_CS
IPR000975 IL-1_fam
IPR003297 IL-1RA/IL-36
IPR008996 IL1/FGF
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

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P18510-1) [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
MEICRGLRSH LITLLLFLFH SETICRPSGR KSSKMQAFRI WDVNQKTFYL
60 70 80 90 100
RNNQLVAGYL QGPNVNLEEK IDVVPIEPHA LFLGIHGGKM CLSCVKSGDE
110 120 130 140 150
TRLQLEAVNI TDLSENRKQD KRFAFIRSDS GPTTSFESAA CPGWFLCTAM
160 170
EADQPVSLTN MPDEGVMVTK FYFQEDE
Length:177
Mass (Da):20,055
Last modified:November 1, 1990 - v1
Checksum:iD1690776A7394057
GO
Isoform 2 (identifier: P18510-2) [UniParc]FASTAAdd to basket
Also known as: icIL-1ra

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MEICRGLRSHLITLLLFLFHS → MAL

Show »
Length:159
Mass (Da):17,888
Checksum:iC1D66CDF0D2F7B44
GO
Isoform 3 (identifier: P18510-3) [UniParc]FASTAAdd to basket
Also known as: icIL-1ra type II

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MEICRGLRSHLITLLLFLFHS → MALADLYEEGGGGGGEGEDNADSK

Show »
Length:180
Mass (Da):19,897
Checksum:i624A1574C2334229
GO
Isoform 4 (identifier: P18510-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: Missing.

Show »
Length:143
Mass (Da):16,142
Checksum:i4CAD6784B890906B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049573124A → T1 PublicationCorresponds to variant dbSNP:rs45507693Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0026511 – 34Missing in isoform 4. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_0026491 – 21MEICR…FLFHS → MAL in isoform 2. 2 PublicationsAdd BLAST21
Alternative sequenceiVSP_0026501 – 21MEICR…FLFHS → MALADLYEEGGGGGGEGEDN ADSK in isoform 3. 2 PublicationsAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53296 mRNA Translation: CAA37386.1
X52015 mRNA Translation: CAA36262.1
M63099 Genomic DNA Translation: AAB41943.1
X64532 Genomic DNA Translation: CAA45832.1
U65590 Genomic DNA Translation: AAB92270.1
U65590 Genomic DNA Translation: AAB92268.1
U65590 Genomic DNA Translation: AAB92269.1
M55646 mRNA Translation: AAA59138.1
X84348 mRNA Translation: CAA59087.1
AY196903 Genomic DNA Translation: AAN87150.1
AK290898 mRNA Translation: BAF83587.1
AK290926 mRNA Translation: BAF83615.1
AC024704 Genomic DNA Translation: AAX93278.1
CH471217 Genomic DNA Translation: EAW73625.1
BC009745 mRNA Translation: AAH09745.1
AF043143 mRNA Translation: AAC39672.1
BN000002 Genomic DNA Translation: CAD29879.1
CCDSiCCDS2113.1 [P18510-2]
CCDS2114.1 [P18510-3]
CCDS2115.1 [P18510-4]
CCDS46396.1 [P18510-1]
PIRiA40956 A30368
I37893 A39386
RefSeqiNP_000568.1, NM_000577.4 [P18510-2]
NP_001305843.1, NM_001318914.1 [P18510-4]
NP_776213.1, NM_173841.2 [P18510-3]
NP_776214.1, NM_173842.2 [P18510-1]
NP_776215.1, NM_173843.2 [P18510-4]
XP_005263718.1, XM_005263661.4 [P18510-4]
XP_011509423.1, XM_011511121.1 [P18510-4]
UniGeneiHs.81134

Genome annotation databases

EnsembliENST00000259206; ENSP00000259206; ENSG00000136689 [P18510-3]
ENST00000354115; ENSP00000329072; ENSG00000136689 [P18510-2]
ENST00000361779; ENSP00000354816; ENSG00000136689 [P18510-4]
ENST00000409052; ENSP00000387210; ENSG00000136689 [P18510-4]
ENST00000409930; ENSP00000387173; ENSG00000136689 [P18510-1]
GeneIDi3557
KEGGihsa:3557
UCSCiuc002tiy.3 human [P18510-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIL1RA_HUMAN
AccessioniPrimary (citable) accession number: P18510
Secondary accession number(s): A8K4G1
, Q14628, Q53SC2, Q7RTZ4, Q96GD6, Q9UPC0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: June 20, 2018
This is version 202 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, Direct protein sequencing, Pharmaceutical, Reference proteome

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