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Protein

Interleukin-1 receptor accessory protein

Gene

Il1rap

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Coreceptor for IL1RL2 in the IL-36 signaling system. Coreceptor with IL1R1 in the IL-1 signaling system. Associates with IL1R1 bound to IL1B to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Recruits TOLLIP to the signaling complex. Does not bind to interleukin-1 alone; binding of IL1RN to IL1R1, prevents its association with IL1R1 to form a signaling complex. The cellular response is modulated through a non-signaling association with the membrane IL1R2 decoy receptor. Secreted forms (isoforms 2 and 3) associate with secreted ligand-bound IL1R2 and increase the affinity of secreted IL1R2 for IL1B; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors. Coreceptor for IL1RL1 in the IL-33 signaling system. Can bidirectionally induce pre- and postsynaptic differentiation of neurons by trans-synaptically binding to PTPRD (PubMed:25908590).1 PublicationBy similarity6 Publications
Isoform 2: Associates with secreted ligand-bound IL1R2 and increases the affinity of secreted IL1R2 for IL1B; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors. Enhances the ability of secreted IL1R1 to inhibit IL-33 signaling.2 Publications
Isoform 3: Required for Src phosphorylation by IL1B. Required for IL1B-potentiated NMDA-induced calcium influx in neurons acting in cooperation with IL1R1 isoform 2 to mediate Akt kinase activation.2 Publications

GO - Molecular functioni

  • interleukin-1 receptor activity Source: MGI
  • interleukin-33 receptor activity Source: UniProtKB
  • protein tyrosine kinase binding Source: MGI
  • signal transducer activity Source: MGI

GO - Biological processi

  • cytokine-mediated signaling pathway Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • interleukin-2 biosynthetic process Source: MGI
  • interleukin-33-mediated signaling pathway Source: UniProtKB
  • interleukin-4 secretion Source: UniProtKB
  • positive regulation of dendrite development Source: MGI
  • positive regulation of interleukin-13 production Source: UniProtKB
  • positive regulation of interleukin-5 production Source: UniProtKB
  • positive regulation of interleukin-6 secretion Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of synapse assembly Source: UniProtKB

Keywordsi

Molecular functionReceptor
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-388844. Receptor protein tyrosine phosphatases interactions.
R-MMU-446652. Interleukin-1 signaling.
R-MMU-449836. Other interleukin signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-1 receptor accessory protein
Short name:
IL-1 receptor accessory protein
Short name:
IL-1RAcP
Alternative name(s):
Interleukin-33 receptot beta chain1 Publication
Gene namesi
Name:Il1rap
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:104975. Il1rap.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 367ExtracellularSequence analysisAdd BLAST347
Transmembranei368 – 388HelicalSequence analysisAdd BLAST21
Topological domaini389 – 570CytoplasmicSequence analysisAdd BLAST182

GO - Cellular componenti

  • extracellular space Source: BHF-UCL
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: MGI
  • plasma membrane Source: Reactome

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi27W → A: Reduces affinity for PTPRD. 1 Publication1
Mutagenesisi30D → A: Does not affect affinity for PTPRD. 1 Publication1
Mutagenesisi69 – 71IWY → AWA: Abolishes interaction with PTPRD; when associates with 82-A--A-85. Significantly reduces synaptogenesis; when associates with 82-A--A-85. 1 Publication3
Mutagenesisi82 – 85PINF → AINA: Abolishes interaction with PTPRD; when associates with 69-A--A-71 Significantly reduces synaptogenesis; when associates with 82-A--A-85. 1 Publication4
Mutagenesisi94K → A: Reduces affinity for PTPRD. 1 Publication1
Mutagenesisi527 – 534KGEKSKYP → AAAAAAAA: Abolishes interaction with MYD88 and IL-1-dependent activation of NF-kappa-B. 1 Publication8

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001545221 – 570Interleukin-1 receptor accessory proteinAdd BLAST550

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi24 ↔ 122PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi47 ↔ 114PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi57N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi107N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi111N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi118N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi137 ↔ 181PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi160 ↔ 212PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi196N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi209N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi266 ↔ 332PROSITE-ProRule annotationCombined sources1 Publication
Glycosylationi299N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PeptideAtlasiQ61730.
PRIDEiQ61730.

PTM databases

iPTMnetiQ61730.
PhosphoSitePlusiQ61730.

Expressioni

Tissue specificityi

Detected in lung, brain, spleen, thymus and liver. Expressed in brain endothelial cells, astrocytes, microglia and neurons. Isoform 3 is predominantly expressed in brain; expressed in hippocampal neurons.4 Publications

Gene expression databases

BgeeiENSMUSG00000022514.
CleanExiMM_IL1RAP.
ExpressionAtlasiQ61730. baseline and differential.
GenevisibleiQ61730. MM.

Interactioni

Subunit structurei

The interleukin-36 receptor complex is a heterodimer of IL1RL2 and IL1RAP; the association is inhibited by IL36RN. The interleukin-1 receptor complex is a heterodimer of IL1R1 and IL1RAP. Associates with IL1R2 to form a non-signaling interleukin-1 receptor complex. Interacts with IL-33-bound IL1RL1 to form the minimal interleukin-33 signaling complex with a 1:1:1 stoichiometry. Interacts with KIT (independently of stimulation with KITLG/SCF). A mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex contains IL1RL1, IL1RAP, KIT and MYD88. Interacts (via the first immunoglobilin domain) with PTPRD (via the third immunoglobilin domain); induces pre- and postsynaptic differentiation of neurons (PubMed:25908590).6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TollipQ9QZ062EBI-525035,EBI-74272

GO - Molecular functioni

  • protein tyrosine kinase binding Source: MGI

Protein-protein interaction databases

BioGridi200628. 3 interactors.
DIPiDIP-296N.
IntActiQ61730. 3 interactors.

Structurei

Secondary structure

1570
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi25 – 29Combined sources5
Beta strandi35 – 38Combined sources4
Beta strandi43 – 46Combined sources4
Helixi48 – 50Combined sources3
Turni51 – 53Combined sources3
Helixi58 – 62Combined sources5
Turni63 – 65Combined sources3
Beta strandi67 – 74Combined sources8
Beta strandi85 – 87Combined sources3
Helixi88 – 90Combined sources3
Beta strandi91 – 95Combined sources5
Beta strandi98 – 103Combined sources6
Helixi106 – 108Combined sources3
Beta strandi110 – 117Combined sources8
Beta strandi123 – 132Combined sources10
Beta strandi146 – 150Combined sources5
Beta strandi156 – 159Combined sources4
Beta strandi174 – 179Combined sources6
Beta strandi188 – 192Combined sources5
Beta strandi194 – 201Combined sources8
Beta strandi208 – 218Combined sources11
Beta strandi221 – 234Combined sources14
Beta strandi250 – 252Combined sources3
Beta strandi267 – 270Combined sources4
Beta strandi279 – 286Combined sources8
Beta strandi296 – 299Combined sources4
Beta strandi302 – 304Combined sources3
Beta strandi310 – 313Combined sources4
Beta strandi315 – 320Combined sources6
Helixi323 – 327Combined sources5
Beta strandi331 – 343Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YFDX-ray3.25B21-351[»]
ProteinModelPortaliQ61730.
SMRiQ61730.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 128Ig-like C2-type 1Add BLAST108
Domaini139 – 230Ig-like C2-type 2Add BLAST92
Domaini243 – 348Ig-like C2-type 3Add BLAST106
Domaini403 – 549TIRPROSITE-ProRule annotationAdd BLAST147

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni69 – 85Essential for interaction with PTPRD1 PublicationAdd BLAST17

Sequence similaritiesi

Belongs to the interleukin-1 receptor family.Curated

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00760000119071.
HOGENOMiHOG000092977.
HOVERGENiHBG104298.
InParanoidiQ61730.
KOiK04723.
OMAiPERCDDW.
OrthoDBiEOG091G0GXW.
PhylomeDBiQ61730.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
3.40.50.10140. 1 hit.
InterProiView protein in InterPro
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR015621. IL-1_rcpt_fam.
IPR004074. IL-1_rcpt_I/II-typ.
IPR000157. TIR_dom.
PANTHERiPTHR11890. PTHR11890. 1 hit.
PfamiView protein in Pfam
PF13895. Ig_2. 1 hit.
PF01582. TIR. 1 hit.
PRINTSiPR01536. INTRLKN1R12F.
SMARTiView protein in SMART
SM00409. IG. 3 hits.
SM00255. TIR. 1 hit.
SUPFAMiSSF48726. SSF48726. 3 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiView protein in PROSITE
PS50835. IG_LIKE. 2 hits.
PS50104. TIR. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q61730-1) [UniParc]FASTAAdd to basket
Also known as: MuIL-1R AcP

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
MGLLWYLMSL SFYGILQSHA SERCDDWGLD TMRQIQVFED EPARIKCPLF
60 70 80 90 100
EHFLKYNYST AHSSGLTLIW YWTRQDRDLE EPINFRLPEN RISKEKDVLW
110 120 130 140 150
FRPTLLNDTG NYTCMLRNTT YCSKVAFPLE VVQKDSCFNS AMRFPVHKMY
160 170 180 190 200
IEHGIHKITC PNVDGYFPSS VKPSVTWYKG CTEIVDFHNV LPEGMNLSFF
210 220 230 240 250
IPLVSNNGNY TCVVTYPENG RLFHLTRTVT VKVVGSPKDA LPPQIYSPND
260 270 280 290 300
RVVYEKEPGE ELVIPCKVYF SFIMDSHNEV WWTIDGKKPD DVTVDITINE
310 320 330 340 350
SVSYSSTEDE TRTQILSIKK VTPEDLRRNY VCHARNTKGE AEQAAKVKQK
360 370 380 390 400
VIPPRYTVEL ACGFGATVFL VVVLIVVYHV YWLEMVLFYR AHFGTDETIL
410 420 430 440 450
DGKEYDIYVS YARNVEEEEF VLLTLRGVLE NEFGYKLCIF DRDSLPGGIV
460 470 480 490 500
TDETLSFIQK SRRLLVVLSP NYVLQGTQAL LELKAGLENM ASRGNINVIL
510 520 530 540 550
VQYKAVKDMK VKELKRAKTV LTVIKWKGEK SKYPQGRFWK QLQVAMPVKK
560 570
SPRWSSNDKQ GLSYSSLKNV
Length:570
Mass (Da):65,741
Last modified:November 1, 1996 - v1
Checksum:i4D4B07E0310AFDC5
GO
Isoform 2 (identifier: Q61730-2) [UniParc]FASTAAdd to basket
Also known as: SmuIL-1R AcP

The sequence of this isoform differs from the canonical sequence as follows:
     351-359: VIPPRYTVE → GNGCTEPMTL
     360-570: Missing.

Show »
Length:360
Mass (Da):41,567
Checksum:iE525471759FF7719
GO
Isoform 3 (identifier: Q61730-3) [UniParc]FASTAAdd to basket
Also known as: IL-1RAcPb

The sequence of this isoform differs from the canonical sequence as follows:
     449-570: IVTDETLSFI...GLSYSSLKNV → NTVEAVFDFI...LSNNNDFYIL

Show »
Length:685
Mass (Da):78,640
Checksum:iE1EEC0B8F4AF720F
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_008054351 – 359VIPPRYTVE → GNGCTEPMTL in isoform 2. 3 Publications9
Alternative sequenceiVSP_008055360 – 570Missing in isoform 2. 3 PublicationsAdd BLAST211
Alternative sequenceiVSP_058171449 – 570IVTDE…SLKNV → NTVEAVFDFIQRSRRMIVVL SPDYVTEKSISMLEFKLGVM CQNSIATKLIVVEYRPLEQP HPGIMQLKESVSFVSWKGEK SKHSGSKFWKALRLALPLRS LSASSGWNESCSSQSDISLD HVQRRSRLKEPPELRSSERV SGAEPAPGTMSKHRGKPSAA CRCCVTYCEGESHLRSKSRA EMHTHPQWETHLCKPPLQES ESQWIQNGTRPEPAPQISAL ALRHFTDLSNNNDFYIL in isoform 3. Add BLAST122

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X85999 mRNA. Translation: CAA59991.1.
AK039582 mRNA. Translation: BAC30392.1.
AK045686 mRNA. Translation: BAC32457.1.
AK136782 mRNA. Translation: BAE23128.1.
AC154234 Genomic DNA. No translation available.
AC154601 Genomic DNA. No translation available.
CT009561 Genomic DNA. No translation available.
BC021159 mRNA. Translation: AAH21159.1.
CCDSiCCDS28089.1. [Q61730-1]
CCDS49815.1. [Q61730-3]
CCDS57023.1. [Q61730-2]
PIRiA57535.
RefSeqiNP_001152790.1. NM_001159318.1. [Q61730-3]
NP_032390.1. NM_008364.2. [Q61730-1]
NP_598864.1. NM_134103.2. [Q61730-2]
UniGeneiMm.253424.

Genome annotation databases

EnsembliENSMUST00000023156; ENSMUSP00000023156; ENSMUSG00000022514. [Q61730-1]
ENSMUST00000096129; ENSMUSP00000093843; ENSMUSG00000022514. [Q61730-3]
ENSMUST00000174202; ENSMUSP00000134202; ENSMUSG00000022514. [Q61730-2]
GeneIDi16180.
KEGGimmu:16180.
UCSCiuc007yve.2. mouse. [Q61730-1]
uc007yvg.2. mouse.

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiIL1AP_MOUSE
AccessioniPrimary (citable) accession number: Q61730
Secondary accession number(s): Q3UVZ1, Q8VCB9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 22, 2003
Last sequence update: November 1, 1996
Last modified: August 30, 2017
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families