IL1A_RAT
ID IL1A_RAT Reviewed; 270 AA.
AC P16598; Q546R9;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Interleukin-1 alpha;
DE Short=IL-1 alpha;
DE Flags: Precursor;
GN Name=Il1a {ECO:0000312|RGD:2890};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2471704; DOI=10.1093/oxfordjournals.jbchem.a122667;
RA Nishida T., Nishino N., Takano M., Sekiguchi Y., Kawai K., Mizuno K.,
RA Nakai S., Masui Y., Hirai Y.;
RT "Molecular cloning and expression of rat interleukin-1 alpha cDNA.";
RL J. Biochem. 105:351-357(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RA Sultana T., Svechnikov K., Weber G., Soeder O.;
RT "Production of recombinant rat testis interleukin-1 alpha precursor form
RT and discovery of a novel splice version lacking the calpain cleavage
RT site.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
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. After
CC binding to its receptor IL1R1 together with its accessory protein
CC IL1RAP, forms the high affinity interleukin-1 receptor complex.
CC Signaling involves the recruitment of adapter molecules such as MYD88,
CC IRAK1 or IRAK4. In turn, mediates the activation of NF-kappa-B and the
CC three MAPK pathways p38, p42/p44 and JNK pathways. Within the cell,
CC acts as an alarmin and cell death results in its liberation in the
CC extracellular space after disruption of the cell membrane to induce
CC inflammation and alert the host to injury or damage. In addition to its
CC role as a danger signal, which occurs when the cytokine is passively
CC released by cell necrosis, directly senses DNA damage and acts as
CC signal for genotoxic stress without loss of cell integrity.
CC {ECO:0000250|UniProtKB:P01583}.
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 -!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
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DR EMBL; D00403; BAA00306.1; -; mRNA.
DR EMBL; AJ245642; CAC03995.1; -; mRNA.
DR PIR; JX0064; JX0064.
DR RefSeq; NP_058715.1; NM_017019.1.
DR AlphaFoldDB; P16598; -.
DR SMR; P16598; -.
DR STRING; 10116.ENSRNOP00000006113; -.
DR BindingDB; P16598; -.
DR GlyGen; P16598; 2 sites.
DR PaxDb; P16598; -.
DR Ensembl; ENSRNOT00000006113; ENSRNOP00000006113; ENSRNOG00000004575.
DR GeneID; 24493; -.
DR KEGG; rno:24493; -.
DR UCSC; RGD:2890; rat.
DR CTD; 3552; -.
DR RGD; 2890; Il1a.
DR eggNOG; ENOG502T3DD; Eukaryota.
DR GeneTree; ENSGT00390000013353; -.
DR InParanoid; P16598; -.
DR OrthoDB; 1513671at2759; -.
DR PhylomeDB; P16598; -.
DR Reactome; R-RNO-448706; Interleukin-1 processing.
DR Reactome; R-RNO-5620971; Pyroptosis.
DR Reactome; R-RNO-9020702; Interleukin-1 signaling.
DR PRO; PR:P16598; -.
DR Proteomes; UP000002494; Chromosome 3.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; ISO:RGD.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IEA:InterPro.
DR GO; GO:0002526; P:acute inflammatory response; IEP:RGD.
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:0006883; P:cellular sodium ion homeostasis; ISO:RGD.
DR GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; ISO:RGD.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
DR GO; GO:0035234; P:ectopic germ cell programmed cell death; ISO:RGD.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:0001660; P:fever generation; IEA:UniProtKB-KW.
DR GO; GO:0007507; P:heart development; IEP:RGD.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0031424; P:keratinization; IDA:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:1904445; P:negative regulation of establishment of Sertoli cell barrier; IDA:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:RGD.
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; IMP:ARUK-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:ARUK-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:RGD.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISO:RGD.
DR GO; GO:1902624; P:positive regulation of neutrophil migration; IMP:RGD.
DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; IDA:RGD.
DR GO; GO:0050714; P:positive regulation of protein secretion; ISO:RGD.
DR GO; GO:0010893; P:positive regulation of steroid biosynthetic process; IDA:RGD.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IDA:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:ARUK-UCL.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:RGD.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:RGD.
DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; IBA:GO_Central.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IDA:RGD.
DR GO; GO:0046688; P:response to copper ion; ISS:UniProtKB.
DR GO; GO:0010332; P:response to gamma radiation; IEP:RGD.
DR GO; GO:0009408; P:response to heat; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0033591; P:response to L-ascorbic acid; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD.
DR GO; GO:0010193; P:response to ozone; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
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; PTHR10078; 1.
DR PANTHER; PTHR10078:SF33; PTHR10078:SF33; 1.
DR Pfam; PF00340; IL1; 1.
DR Pfam; PF02394; IL1_propep; 1.
DR PRINTS; PR00264; INTERLEUKIN1.
DR PRINTS; PR01358; INTRLEUKIN1A.
DR SUPFAM; SSF50353; SSF50353; 1.
DR PROSITE; PS00253; INTERLEUKIN_1; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cytokine; Cytoplasm; Glycoprotein; Inflammatory response;
KW Mitogen; Nucleus; Phosphoprotein; Pyrogen; Reference proteome; Secreted.
FT PROPEP 1..114
FT /id="PRO_0000015279"
FT CHAIN 115..270
FT /note="Interleukin-1 alpha"
FT /id="PRO_0000015280"
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:0000250|UniProtKB:P01582"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 270 AA; 30856 MW; E3EB22F576F291DE CRC64;
MAKVPDLFED LKNCYSENEE YSSAIDHLSL NQKSFYDASY GSLHENCTDK FVSLRTSETS
KMSTFTFKES RVVVSATSNK GKILKKRRLS FNQPFTEDDL EAIAHDLEET IQPRSAPHSF
QNNLRYKLIR IVKQEFIMND SLNQNIYVDM DRIHLKAASL NDLQLEVKFD MYAYSSGGDD
SKYPVTLKVS NTQLFVSAQG EDKPVLLKEI PETPKLITGS ETDLIFFWEK INSKNYFTSA
AFPELLIATK EQSQVHLARG LPSMIDFQIS
