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   24-JAN-2024, entry version 176.
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   GlyCosmos; P25085; 1 site, No reported glycans.
DR   GlyGen; P25085; 2 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P25085; -.
DR   PhosphoSitePlus; P25085; -.
DR   SwissPalm; P25085; -.
DR   PaxDb; 10090-ENSMUSP00000110126; -.
DR   PeptideAtlas; P25085; -.
DR   ProteomicsDB; 267318; -. [P25085-1]
DR   ProteomicsDB; 267319; -. [P25085-2]
DR   Antibodypedia; 806; 963 antibodies from 43 providers.
DR   DNASU; 16181; -.
DR   Ensembl; ENSMUST00000114482.3; ENSMUSP00000110126.2; ENSMUSG00000026981.16. [P25085-1]
DR   Ensembl; ENSMUST00000114487.9; ENSMUSP00000110131.3; ENSMUSG00000026981.16. [P25085-2]
DR   GeneID; 16181; -.
DR   KEGG; mmu:16181; -.
DR   UCSC; uc008iox.2; mouse. [P25085-1]
DR   AGR; MGI:96547; -.
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   OrthoDB; 4292752at2759; -.
DR   PhylomeDB; P25085; -.
DR   TreeFam; TF300203; -.
DR   Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR   BioGRID-ORCS; 16181; 4 hits in 78 CRISPR screens.
DR   PRO; PR:P25085; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; P25085; Protein.
DR   Bgee; ENSMUSG00000026981; Expressed in granulocyte and 62 other cell types or tissues.
DR   ExpressionAtlas; P25085; baseline and differential.
DR   GO; GO:0005813; C:centrosome; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005576; C:extracellular region; IDA:MGI.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; 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: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:0051384; P:response to glucocorticoid; ISO:MGI.
DR   CDD; cd00100; IL1; 1.
DR   Gene3D; 2.80.10.50; -; 1.
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   PANTHER; PTHR10078; INTERLEUKIN-1 FAMILY MEMBER; 1.
DR   PANTHER; PTHR10078:SF28; INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN; 1.
DR   Pfam; PF00340; IL1; 1.
DR   PRINTS; PR00264; INTERLEUKIN1.
DR   PRINTS; PR01360; INTRLEUKIN1X.
DR   SMART; SM00125; IL1; 1.
DR   SUPFAM; SSF50353; Cytokine; 1.
DR   PROSITE; PS00253; INTERLEUKIN_1; 1.
DR   Genevisible; P25085; MM.
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
//