ID   IL1A_MOUSE              Reviewed;         270 AA.
AC   P01582;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   02-SEP-2026, entry version 196.
DE   RecName: Full=Interleukin-1 alpha;
DE            Short=IL-1 alpha;
DE   Flags: Precursor;
GN   Name=Il1a {ECO:0000312|MGI:MGI:96542};
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 [MRNA].
RX   PubMed=6209582; DOI=10.1038/312458a0;
RA   Lomedico P.T., Gubler U., Hellmann C.P., Dukovich M., Giri J.G.,
RA   Pan Y.-C.E., Collier K., Semionow R., Chua A.O., Mizel S.B.;
RT   "Cloning and expression of murine interleukin-1 cDNA in Escherichia coli.";
RL   Nature 312:458-462(1984).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=BALB/cJ;
RA   Kastelic T., Wanner A., Mackenzie A., Cheneval D.;
RT   "Complete nucleotide sequence of the murine interleukin-1 alpha gene.";
RL   Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   PHOSPHORYLATION AT SER-90.
RX   PubMed=3126184; DOI=10.1016/s0021-9258(18)69027-1;
RA   Beuscher H.U., Nickells M.W., Colten H.R.;
RT   "The precursor of interleukin-1 alpha is phosphorylated at residue serine
RT   90.";
RL   J. Biol. Chem. 263:4023-4028(1988).
RN   [5]
RP   FUNCTION.
RX   PubMed=1386364; DOI=10.1016/s0021-9258(19)49611-7;
RA   Stylianou E., O'Neill L.A., Rawlinson L., Edbrooke M.R., Woo P.,
RA   Saklatvala J.;
RT   "Interleukin 1 induces NF-kappa B through its type I but not its type II
RT   receptor in lymphocytes.";
RL   J. Biol. Chem. 267:15836-15841(1992).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=16256210; DOI=10.1016/j.bbr.2005.09.024;
RA   Honore P., Wade C.L., Zhong C., Harris R.R., Wu C., Ghayur T., Iwakura Y.,
RA   Decker M.W., Faltynek C., Sullivan J., Jarvis M.F.;
RT   "Interleukin-1alphabeta gene-deficient mice show reduced nociceptive
RT   sensitivity in models of inflammatory and neuropathic pain but not post-
RT   operative pain.";
RL   Behav. Brain Res. 167:355-364(2006).
CC   -!- FUNCTION: Cytokine constitutively present intracellularly in nearly all
CC       resting non-hematopoietic cells that plays an important role in
CC       inflammation and bridges the innate and adaptive immune systems
CC       (PubMed:16256210). After binding to its receptor IL1R1 together with
CC       its accessory protein IL1RAP, forms the high affinity interleukin-1
CC       receptor complex. Signaling involves the recruitment of adapter
CC       molecules such as MYD88, IRAK1 or IRAK4. In turn, mediates the
CC       activation of NF-kappa-B and the three MAPK pathways p38, p42/p44 and
CC       JNK pathways (PubMed:1386364). Within the cell, acts as an alarmin and
CC       cell death results in its liberation in the extracellular space after
CC       disruption of the cell membrane to induce inflammation and alert the
CC       host to injury or damage. In addition to its role as a danger signal,
CC       which occurs when the cytokine is passively released by cell necrosis,
CC       directly senses DNA damage and acts as a signal for genotoxic stress
CC       without loss of cell integrity (By similarity).
CC       {ECO:0000250|UniProtKB:P01583, ECO:0000269|PubMed:1386364,
CC       ECO:0000269|PubMed:16256210}.
CC   -!- SUBUNIT: Monomer. Interacts with TMED10; the interaction mediates the
CC       translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-
CC       Golgi intermediate compartment) and thereby secretion. Interacts with
CC       IL1R1. Interacts with S100A13; this interaction is the first step in
CC       the export of IL1A, followed by direct translocation of this complex
CC       across the plasma membrane. {ECO:0000250|UniProtKB:P01583}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P01583}. Cytoplasm
CC       {ECO:0000250|UniProtKB:P01583}. Secreted
CC       {ECO:0000250|UniProtKB:P01583}. Note=The lack of a specific hydrophobic
CC       segment in the precursor sequence suggests that IL-1 is released by
CC       damaged cells or is secreted by a mechanism differing from that used
CC       for other secretory proteins. The secretion is dependent on protein
CC       unfolding and facilitated by the cargo receptor TMED10; it results in
CC       protein translocation from the cytoplasm into the ERGIC (endoplasmic
CC       reticulum-Golgi intermediate compartment) followed by vesicle entry and
CC       secretion. Recruited to DNA damage sites and secreted after genotoxic
CC       stress. {ECO:0000250|UniProtKB:P01583}.
CC   -!- DOMAIN: The similarity among the IL-1 precursors suggests that the
CC       amino ends of these proteins serve some as yet undefined function.
CC   -!- PTM: Acetylated within its nuclear localization sequence, which impacts
CC       subcellular localization. {ECO:0000250|UniProtKB:P01583}.
CC   -!- PTM: Proteolytic processed by CAPN1 in a calcium-dependent manner.
CC       Cleavage from 31 kDa precursor to 18 kDa biologically active molecules.
CC       {ECO:0000250|UniProtKB:P01583}.
CC   -!- PTM: Phosphorylated. Phosphorylation greatly enhances susceptibility to
CC       digestion and promotes the conversion of pre-IL1A alpha to the
CC       biologically active IL1A. {ECO:0000250|UniProtKB:P01583}.
CC   -!- DISRUPTION PHENOTYPE: Deletion mice show reduced nociceptive
CC       sensitivity compared to control mice in models of inflammatory and
CC       nerve injury-induced pain when associated with IL1B deletion.
CC       {ECO:0000269|PubMed:16256210}.
CC   -!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X01450; CAA25682.1; -; mRNA.
DR   EMBL; AF010237; AAC28999.1; -; Genomic_DNA.
DR   EMBL; BC003727; AAH03727.1; -; mRNA.
DR   CCDS; CCDS16725.1; -.
DR   PIR; A01846; ICMS1.
DR   RefSeq; NP_034684.2; NM_010554.4.
DR   AlphaFoldDB; P01582; -.
DR   SMR; P01582; -.
DR   BioGRID; 200623; 1.
DR   CORUM; P01582; -.
DR   FunCoup; P01582; 662.
DR   STRING; 10090.ENSMUSP00000028882; -.
DR   GlyCosmos; P01582; 3 sites, No reported glycans.
DR   GlyGen; P01582; 3 sites.
DR   iPTMnet; P01582; -.
DR   PhosphoSitePlus; P01582; -.
DR   PaxDb; 10090-ENSMUSP00000028882; -.
DR   ProteomicsDB; 269391; -.
DR   Antibodypedia; 3842; 1606 antibodies from 51 providers.
DR   DNASU; 16175; -.
DR   Ensembl; ENSMUST00000028882.2; ENSMUSP00000028882.2; ENSMUSG00000027399.2.
DR   GeneID; 16175; -.
DR   KEGG; mmu:16175; -.
DR   UCSC; uc008mhr.1; mouse.
DR   AGR; MGI:96542; -.
DR   CTD; 3552; -.
DR   MGI; MGI:96542; Il1a.
DR   VEuPathDB; HostDB:ENSMUSG00000027399; -.
DR   eggNOG; ENOG502T3DD; Eukaryota.
DR   GeneTree; ENSGT00390000013353; -.
DR   HOGENOM; CLU_090014_0_0_1; -.
DR   InParanoid; P01582; -.
DR   OMA; SNMKYNF; -.
DR   OrthoDB; 9451248at2759; -.
DR   PhylomeDB; P01582; -.
DR   Reactome; R-MMU-448706; Interleukin-1 processing.
DR   Reactome; R-MMU-5620971; Pyroptosis.
DR   Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR   BioGRID-ORCS; 16175; 0 hits in 78 CRISPR screens.
DR   PRO; PR:P01582; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; P01582; protein.
DR   Bgee; ENSMUSG00000027399; Expressed in esophagus and 30 other cell types or tissues.
DR   ExpressionAtlas; P01582; baseline and differential.
DR   GO; GO:0009986; C:cell surface; ISO:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IDA:MGI.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR   GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR   GO; GO:0005149; F:interleukin-1 receptor binding; IEA:InterPro.
DR   GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central.
DR   GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; IMP:MGI.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:GO_Central.
DR   GO; GO:0035234; P:ectopic germ cell programmed cell death; IGI:MGI.
DR   GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IMP:MGI.
DR   GO; GO:0006955; P:immune response; IBA:GO_Central.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0006883; P:intracellular sodium ion homeostasis; IDA:MGI.
DR   GO; GO:0031424; P:keratinization; ISO:GO_Central.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:GO_Central.
DR   GO; GO:1904445; P:negative regulation of establishment of Sertoli cell barrier; ISO:GO_Central.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISO:GO_Central.
DR   GO; GO:0001819; P:positive regulation of cytokine production; ISO:GO_Central.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:GO_Central.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:GO_Central.
DR   GO; GO:0033092; P:positive regulation of immature T cell proliferation in thymus; IBA:GO_Central.
DR   GO; GO:0032743; P:positive regulation of interleukin-2 production; ISO:GO_Central.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:GO_Central.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; ISO:GO_Central.
DR   GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISO:GO_Central.
DR   GO; GO:1902624; P:positive regulation of neutrophil migration; ISO:GO_Central.
DR   GO; GO:0032308; P:positive regulation of prostaglandin secretion; ISO:GO_Central.
DR   GO; GO:0050714; P:positive regulation of protein secretion; ISO:GO_Central.
DR   GO; GO:0010893; P:positive regulation of steroid biosynthetic process; ISO:GO_Central.
DR   GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; ISO:GO_Central.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR   GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:GO_Central.
DR   GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IMP:BHF-UCL.
DR   GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:GO_Central.
DR   GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR   GO; GO:0046688; P:response to copper ion; ISS:UniProtKB.
DR   CDD; cd23295; beta-trefoil_IL1A; 1.
DR   FunFam; 2.80.10.50:FF:000049; Interleukin-1 alpha; 1.
DR   Gene3D; 2.80.10.50; -; 1.
DR   InterPro; IPR003295; IL-1_alpha.
DR   InterPro; IPR020877; IL-1_CS.
DR   InterPro; IPR000975; IL-1_fam.
DR   InterPro; IPR003502; IL-1_propep.
DR   InterPro; IPR008996; IL1/FGF.
DR   PANTHER; PTHR10078:SF33; INTERLEUKIN-1 ALPHA; 1.
DR   PANTHER; PTHR10078; INTERLEUKIN-1 FAMILY MEMBER; 1.
DR   Pfam; PF00340; IL1; 1.
DR   Pfam; PF02394; IL1_propep; 1.
DR   PRINTS; PR00264; INTERLEUKIN1.
DR   PRINTS; PR01358; INTRLEUKIN1A.
DR   PRINTS; PR01357; INTRLEUKN1AB.
DR   SMART; SM00125; IL1; 1.
DR   SUPFAM; SSF50353; Cytokine; 1.
DR   PROSITE; PS00253; INTERLEUKIN_1; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Cytokine; Cytoplasm; Glycoprotein; Inflammatory response;
KW   Mitogen; Nucleus; Phosphoprotein; Pyrogen; Reference proteome; Secreted.
FT   PROPEP          1..114
FT                   /id="PRO_0000015273"
FT   CHAIN           115..270
FT                   /note="Interleukin-1 alpha"
FT                   /id="PRO_0000015274"
FT   REGION          85..89
FT                   /note="Nuclear localization signal (NLS)"
FT                   /evidence="ECO:0000250|UniProtKB:P01583"
FT   MOD_RES         85
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P01583"
FT   MOD_RES         90
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:3126184"
FT   CARBOHYD        64
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        143
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   270 AA;  31023 MW;  7F60AC4F330D5B11 CRC64;
     MAKVPDLFED LKNCYSENED YSSAIDHLSL NQKSFYDASY GSLHETCTDQ FVSLRTSETS
     KMSNFTFKES RVTVSATSSN GKILKKRRLS FSETFTEDDL QSITHDLEET IQPRSAPYTY
     QSDLRYKLMK LVRQKFVMND SLNQTIYQDV DKHYLSTTWL NDLQQEVKFD MYAYSSGGDD
     SKYPVTLKIS DSQLFVSAQG EDQPVLLKEL PETPKLITGS ETDLIFFWKS INSKNYFTSA
     AYPELFIATK EQSRVHLARG LPSMTDFQIS
//