ID   IL1A_CERAT              Reviewed;         271 AA.
AC   P46647;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   03-AUG-2022, entry version 87.
DE   RecName: Full=Interleukin-1 alpha;
DE            Short=IL-1 alpha;
DE   Flags: Precursor;
GN   Name=IL1A;
OS   Cercocebus atys (Sooty mangabey) (Cercocebus torquatus atys).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Cercocebus.
OX   NCBI_TaxID=9531;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Blood;
RX   PubMed=7561102;
RA   Villinger F.J., Brar S.S., Mayne A.E., Chikkala N., Ansari A.A.;
RT   "Comparative sequence analysis of cytokine genes from human and nonhuman
RT   primates.";
RL   J. Immunol. 155:3946-3954(1995).
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; U19836; AAA86703.1; -; mRNA.
DR   AlphaFoldDB; P46647; -.
DR   SMR; P46647; -.
DR   STRING; 9531.ENSCATP00000036036; -.
DR   Proteomes; UP000233060; Whole Genome Shotgun Assembly.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
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:0001660; P:fever generation; IEA:UniProtKB-KW.
DR   GO; GO:0006955; P:immune response; IEA:InterPro.
DR   GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR   GO; GO:0001819; P:positive regulation of cytokine production; IEA:UniProt.
DR   GO; GO:0046688; P:response to copper ion; ISS:UniProtKB.
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..112
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000015259"
FT   CHAIN           113..271
FT                   /note="Interleukin-1 alpha"
FT                   /id="PRO_0000015260"
FT   REGION          82..86
FT                   /note="Nuclear localization signal (NLS)"
FT                   /evidence="ECO:0000250|UniProtKB:P01583"
FT   MOD_RES         82
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P01583"
FT   MOD_RES         87
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P01582"
FT   CARBOHYD        102
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   271 AA;  30451 MW;  19BDFB29A5D51A58 CRC64;
     MAKVPDMFED LKNCYSENEE DSSSIDHLFL NQKSFYDVSY GPLHESCMDQ SVSLSISEIS
     KTSKLSFKQS MVVVSTNGKV LKKRRLSLSQ SIADDNLEAI ANDSEEEIIK PRSAPFSFLS
     NMTYHIIRII KHESILNDTL NQTIIRANDQ YLTAAAIHNL DEAVKFDMGA YTSSKDDTKV
     PVILRISKTQ LYVSAQDEDQ PVLLKEMPEI PKTTTGGETN SLSSWETRGT KNYFISVAHP
     NLFIATKHDN WVCLAKGLPS ITDFQILENQ A