IL1RA_MOUSE
ID IL1RA_MOUSE Reviewed; 178 AA.
AC P25085; O70207;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Interleukin-1 receptor antagonist protein;
DE Short=IL-1RN;
DE Short=IL-1ra;
DE Short=IRAP;
DE AltName: Full=IL1 inhibitor;
DE Flags: Precursor;
GN Name=Il1rn; Synonyms=Il-1ra;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RX PubMed=1828262;
RA Zahedi K., Seldin M.F., Rits M., Ezekowitz R.A., Whitehead A.S.;
RT "Mouse IL-1 receptor antagonist protein. Molecular characterization, gene
RT mapping, and expression of mRNA in vitro and in vivo.";
RL J. Immunol. 146:4228-4233(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1830498;
RA Matsushime H., Roussel M.F., Matsushima K., Hishinuma A., Sherr C.J.;
RT "Cloning and expression of murine interleukin-1 receptor antagonist in
RT macrophages stimulated by colony-stimulating factor 1.";
RL Blood 78:616-623(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC STRAIN=SWR/J;
RX PubMed=8003626; DOI=10.1016/1043-4666(94)90001-9;
RA Zahedi K.A., Uhlar C.M., Rits M., Prada A.E., Whitehead A.S.;
RT "The mouse interleukin 1 receptor antagonist protein: gene structure and
RT regulation in vitro.";
RL Cytokine 6:1-9(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=FVB X DBA/1 LACJ;
RX PubMed=9550387;
RA Gabay C., Porter B., Fantuzzi G., Arend W.P.;
RT "Mouse IL-1 receptor antagonist isoforms: complementary DNA cloning and
RT protein expression of intracellular isoform and tissue distribution of
RT secreted and intracellular IL-1 receptor antagonist in vivo.";
RL J. Immunol. 159:5905-5913(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 7-178.
RX PubMed=1828896; DOI=10.1073/pnas.88.12.5232;
RA Eisenberg S.P., Brewer M.T., Verderber E., Heimdal P., Brandhuber B.J.,
RA Thompson R.C.;
RT "Interleukin 1 receptor antagonist is a member of the interleukin 1 gene
RT family: evolution of a cytokine control mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:5232-5236(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE OF 23-178.
RX PubMed=1834470; DOI=10.1002/eji.1830211119;
RA Shuck M.E., Eessalu T.E., Tracey D.E., Bienkowski M.J.;
RT "Cloning, heterologous expression and characterization of murine
RT interleukin 1 receptor antagonist protein.";
RL Eur. J. Immunol. 21:2775-2780(1991).
RN [7]
RP FUNCTION.
RX PubMed=31611644; DOI=10.1038/s41564-019-0578-3;
RA Ji D.X., Yamashiro L.H., Chen K.J., Mukaida N., Kramnik I., Darwin K.H.,
RA Vance R.E.;
RT "Type I interferon-driven susceptibility to Mycobacterium tuberculosis is
RT mediated by IL-1Ra.";
RL Nat. Microbiol. 4:2128-2135(2019).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=35332327; DOI=10.1038/s41590-022-01160-y;
RA Tahtinen S., Tong A.J., Himmels P., Oh J., Paler-Martinez A., Kim L.,
RA Wichner S., Oei Y., McCarron M.J., Freund E.C., Amir Z.A., de la Cruz C.C.,
RA Haley B., Blanchette C., Schartner J.M., Ye W., Yadav M., Sahin U.,
RA Delamarre L., Mellman I.;
RT "IL-1 and IL-1ra are key regulators of the inflammatory response to RNA
RT vaccines.";
RL Nat. Immunol. 23:532-542(2022).
CC -!- FUNCTION: Anti-inflammatory antagonist of interleukin-1 family of
CC proinflammatory cytokines such as interleukin-1beta/IL1B and
CC interleukin-1alpha/IL1A. Protects from immune dysregulation and
CC uncontrolled systemic inflammation triggered by IL1 for a range of
CC innate stimulatory agents such as pathogens.
CC {ECO:0000269|PubMed:31611644, ECO:0000269|PubMed:35332327}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted
CC {ECO:0000250|UniProtKB:P18510}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P25085-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P25085-2; Sequence=VSP_002652;
CC -!- DISRUPTION PHENOTYPE: Deficient mice still possess other negative
CC regulators of IL1 activity and adapt to excessive IL1 via shedding of
CC IL1R1. {ECO:0000269|PubMed:35332327}.
CC -!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
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DR EMBL; M74294; AAA39309.1; -; mRNA.
DR EMBL; M64404; AAA39277.1; -; mRNA.
DR EMBL; L32838; AAA20576.1; -; Genomic_DNA.
DR EMBL; AF001795; AAC15251.1; -; mRNA.
DR EMBL; M57525; AAA39278.1; -; mRNA.
DR EMBL; M63100; AAA39310.1; -; Genomic_DNA.
DR EMBL; S64082; AAB20265.1; -; mRNA.
DR CCDS; CCDS15736.1; -. [P25085-2]
DR CCDS; CCDS38064.1; -. [P25085-1]
DR PIR; A44610; A44610.
DR RefSeq; NP_001034790.1; NM_001039701.3. [P25085-1]
DR RefSeq; NP_112444.1; NM_031167.5. [P25085-2]
DR AlphaFoldDB; P25085; -.
DR SMR; P25085; -.
DR STRING; 10090.ENSMUSP00000110126; -.
DR BindingDB; P25085; -.
DR ChEMBL; CHEMBL3414413; -.
DR GlyGen; P25085; 1 site.
DR iPTMnet; P25085; -.
DR PhosphoSitePlus; P25085; -.
DR SwissPalm; P25085; -.
DR PaxDb; P25085; -.
DR PeptideAtlas; P25085; -.
DR PRIDE; P25085; -.
DR ProteomicsDB; 267318; -. [P25085-1]
DR ProteomicsDB; 267319; -. [P25085-2]
DR Antibodypedia; 806; 893 antibodies from 43 providers.
DR DNASU; 16181; -.
DR Ensembl; ENSMUST00000114482; ENSMUSP00000110126; ENSMUSG00000026981. [P25085-1]
DR Ensembl; ENSMUST00000114487; ENSMUSP00000110131; ENSMUSG00000026981. [P25085-2]
DR GeneID; 16181; -.
DR KEGG; mmu:16181; -.
DR UCSC; uc008iox.2; mouse. [P25085-1]
DR CTD; 3557; -.
DR MGI; MGI:96547; Il1rn.
DR VEuPathDB; HostDB:ENSMUSG00000026981; -.
DR eggNOG; ENOG502S5F0; Eukaryota.
DR GeneTree; ENSGT00950000182943; -.
DR HOGENOM; CLU_095373_2_0_1; -.
DR InParanoid; P25085; -.
DR OMA; WYLCTAL; -.
DR PhylomeDB; P25085; -.
DR TreeFam; TF300203; -.
DR Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR BioGRID-ORCS; 16181; 4 hits in 73 CRISPR screens.
DR PRO; PR:P25085; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P25085; protein.
DR Bgee; ENSMUSG00000026981; Expressed in granulocyte and 60 other tissues.
DR ExpressionAtlas; P25085; baseline and differential.
DR Genevisible; P25085; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0031982; C:vesicle; IDA:MGI.
DR GO; GO:0005125; F:cytokine activity; IEA:InterPro.
DR GO; GO:0005152; F:interleukin-1 receptor antagonist activity; ISO:MGI.
DR GO; GO:0005149; F:interleukin-1 receptor binding; ISO:MGI.
DR GO; GO:0045352; F:interleukin-1 type I receptor antagonist activity; ISO:MGI.
DR GO; GO:0045353; F:interleukin-1 type II receptor antagonist activity; ISO:MGI.
DR GO; GO:0005150; F:interleukin-1, type I receptor binding; ISO:MGI.
DR GO; GO:0005151; F:interleukin-1, type II receptor binding; ISO:MGI.
DR GO; GO:0006953; P:acute-phase response; ISO:MGI.
DR GO; GO:0001660; P:fever generation; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IBA:GO_Central.
DR GO; GO:0030073; P:insulin secretion; IMP:MGI.
DR GO; GO:0006629; P:lipid metabolic process; IMP:MGI.
DR GO; GO:0007613; P:memory; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:MGI.
DR GO; GO:0014050; P:negative regulation of glutamate secretion; ISO:MGI.
DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; ISO:MGI.
DR GO; GO:2000660; P:negative regulation of interleukin-1-mediated signaling pathway; ISO:MGI.
DR GO; GO:0045837; P:negative regulation of membrane potential; ISO:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:MGI.
DR GO; GO:0051384; P:response to glucocorticoid; ISO:MGI.
DR GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR InterPro; IPR020877; IL-1_CS.
DR InterPro; IPR000975; IL-1_fam.
DR InterPro; IPR003297; IL-1RA/IL-36.
DR InterPro; IPR008996; IL1/FGF.
DR InterPro; IPR039348; IL1RA.
DR PANTHER; PTHR10078; PTHR10078; 1.
DR PANTHER; PTHR10078:SF28; PTHR10078:SF28; 1.
DR Pfam; PF00340; IL1; 1.
DR PRINTS; PR00264; INTERLEUKIN1.
DR PRINTS; PR01360; INTRLEUKIN1X.
DR SUPFAM; SSF50353; SSF50353; 1.
DR PROSITE; PS00253; INTERLEUKIN_1; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasm; Disulfide bond; Glycoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000250"
FT CHAIN 27..178
FT /note="Interleukin-1 receptor antagonist protein"
FT /id="PRO_0000015330"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 92..142
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..21
FT /note="MEICWGPYSHLISLLLILLFH -> MA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9550387"
FT /id="VSP_002652"
SQ SEQUENCE 178 AA; 20274 MW; 84AA002A3119C024 CRC64;
MEICWGPYSH LISLLLILLF HSEAACRPSG KRPCKMQAFR IWDTNQKTFY LRNNQLIAGY
LQGPNIKLEE KIDMVPIDLH SVFLGIHGGK LCLSCAKSGD DIKLQLEEVN ITDLSKNKEE
DKRFTFIRSE KGPTTSFESA ACPGWFLCTT LEADRPVSLT NTPEEPLIVT KFYFQEDQ
