ID IL1A_HUMAN Reviewed; 271 AA. AC P01583; Q53QF9; Q7RU02; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 04-NOV-2026, entry version 242. DE RecName: Full=Interleukin-1 alpha; DE Short=IL-1 alpha; DE AltName: Full=Hematopoietin-1; DE Flags: Precursor; GN Name=IL1A; Synonyms=IL1F1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2989698; DOI=10.1038/315641a0; RA March C.J., Mosley B., Larsen A., Cerretti D.P., Braedt G., Price V., RA Gillis S., Henney C.S., Kronheim S.R., Grabstein K., Conlon P.J., RA Hopp T.P., Cosman D.; RT "Cloning, sequence and expression of two distinct human interleukin-1 RT complementary DNAs."; RL Nature 315:641-647(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3486405; DOI=10.1093/nar/14.8.3167; RA Furutani Y., Notake M., Fukui T., Ohue M., Nomura H., Yamada M., RA Nakamura S.; RT "Complete nucleotide sequence of the gene for human interleukin 1 alpha."; RL Nucleic Acids Res. 14:3167-3179(1986). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-114. RX PubMed=2994016; DOI=10.1093/nar/13.16.5869; RA Furutani Y., Notake M., Yamayoshi M., Yamagishi J., Nomura H., Ohue M., RA Furuta R., Fukui T., Yamada M., Nakamura S.; RT "Cloning and characterization of the cDNAs for human and rabbit RT interleukin-1 precursor."; RL Nucleic Acids Res. 13:5869-5882(1985). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-114. RX PubMed=2635664; RA Kotenko S.V., Bulenkov M.T., Veiko V.P., Epishin S.M., Lomakin I.B., RA Emel'Yanov A.V., Kozlov A.P., Konusova V.G., Kotov A.Y., Kurbatova T.V., RA Reshetnikov V.L., Simbirtsev A.S., Ketlinskii S.A., Vinetskii Y.P.; RT "Cloning of the cDNA coding for human prointerleukin-1 alpha and RT prointerleukin-1 beta."; RL Dokl. Akad. Nauk SSSR 309:1005-1008(1989). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3485152; DOI=10.4049/jimmunol.136.7.2492; RA Gubler U., Chua A.O., Stern A.S., Hellmann C.P., Vitek M.P., Dechiara T.M., RA Benjamin W.R., Collier K.J., Dukovich M., Familletti P.C., Fiedler-Nagy C., RA Jenson J., Kaffka K., Kilian P.L., Stremlo D., Wittreich B.H., Woehle D., RA Mizel S.B., Lomedico P.T.; RT "Recombinant human interleukin 1 alpha: purification and biological RT characterization."; RL J. Immunol. 136:2492-2497(1986). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3493774; DOI=10.1016/0006-291x(87)90671-1; RA Nishida T., Nishino N., Takano M., Kawai K., Bando K., Masui Y., Nakai S., RA Hirai Y.; RT "cDNA cloning of IL-1 alpha and IL-1 beta from mRNA of U937 cell line."; RL Biochem. Biophys. Res. Commun. 143:345-352(1987). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11991722; DOI=10.1006/geno.2002.6751; RA Nicklin M.J.H., Barton J.L., Nguyen M., Fitzgerald M.G., Duff W.G., RA Kornman K.; RT "A sequence-based map of the nine genes of the human interleukin-1 RT cluster."; RL Genomics 79:718-725(2002). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-85; SER-114 AND RP ASN-138. RG SeattleSNPs variation discovery resource; RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; 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 [15] RP PROTEIN SEQUENCE OF 113-132. RX PubMed=3281727; DOI=10.1182/blood.v71.4.962.962; RA Zsebo K.M., Wypych J., Yuschenkoff V.N., Lu H., Hunt P., Dukes P.P., RA Langley K.E.; RT "Effects of hematopoietin-1 and interleukin 1 activities on early RT hematopoietic cells of the bone marrow."; RL Blood 71:962-968(1988). RN [16] RP FUNCTION, AND INTERACTION WITH IL1R1. RX PubMed=2950091; DOI=10.1016/s0021-9258(18)61450-4; RA Mosley B., Urdal D.L., Prickett K.S., Larsen A., Cosman D., Conlon P.J., RA Gillis S., Dower S.K.; RT "The interleukin-1 receptor binds the human interleukin-1 alpha precursor RT but not the interleukin-1 beta precursor."; RL J. Biol. Chem. 262:2941-2944(1987). RN [17] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=3258335; DOI=10.4049/jimmunol.140.7.2279; RA Kobayashi Y., Appella E., Yamada M., Copeland T.D., Oppenheim J.J., RA Matsushima K.; RT "Phosphorylation of intracellular precursors of human IL-1."; RL J. Immunol. 140:2279-2287(1988). RN [18] RP CLEAVAGE BY CAPN1. RX PubMed=2115174; DOI=10.1073/pnas.87.14.5548; RA Kobayashi Y., Yamamoto K., Saido T., Kawasaki H., Oppenheim J.J., RA Matsushima K.; RT "Identification of calcium-activated neutral protease as a processing RT enzyme of human interleukin 1 alpha."; RL Proc. Natl. Acad. Sci. U.S.A. 87:5548-5552(1990). RN [19] RP MYRISTOYLATION AT LYS-82 AND LYS-83. RX PubMed=8346241; DOI=10.1073/pnas.90.15.7245; RA Stevenson F.T., Bursten S.L., Fanton C., Locksley R.M., Lovett D.H.; RT "The 31-kDa precursor of interleukin 1 alpha is myristoylated on specific RT lysines within the 16-kDa N-terminal propiece."; RL Proc. Natl. Acad. Sci. U.S.A. 90:7245-7249(1993). RN [20] RP FUNCTION. RX PubMed=14687581; DOI=10.1016/j.cyto.2003.08.013; RA Wu T., Han C., Shelhamer J.H.; RT "Involvement of p38 and p42/44 MAP kinases and protein kinase C in the RT interferon-gamma and interleukin-1alpha-induced phosphorylation of 85-kDa RT cytosolic phospholipase A(2) in primary human bronchial epithelial cells."; RL Cytokine 25:11-20(2004). RN [21] RP FUNCTION AS ALARMIN. RX PubMed=15679580; DOI=10.1111/j.0906-6705.2005.00226.x; RA Spiekstra S.W., Toebak M.J., Sampat-Sardjoepersad S., van Beek P.J., RA Boorsma D.M., Stoof T.J., von Blomberg B.M., Scheper R.J., Bruynzeel D.P., RA Rustemeyer T., Gibbs S.; RT "Induction of cytokine (interleukin-1alpha and tumor necrosis factor-alpha) RT and chemokine (CCL20, CCL27, and CXCL8) alarm signals after allergen and RT irritant exposure."; RL Exp. Dermatol. 14:109-116(2005). RN [22] RP FUNCTION. RX PubMed=17507369; DOI=10.1074/mcp.m600455-mcp200; RA Brikos C., Wait R., Begum S., O'Neill L.A., Saklatvala J.; RT "Mass spectrometric analysis of the endogenous type I interleukin-1 (IL-1) RT receptor signaling complex formed after IL-1 binding identifies IL-1RAcP, RT MyD88, and IRAK-4 as the stable components."; RL Mol. Cell. Proteomics 6:1551-1559(2007). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, ACETYLATION AT LYS-82, MUTAGENESIS OF RP LYS-82, AND NUCLEAR LOCALIZATION SIGNAL. RX PubMed=26439902; DOI=10.1038/srep14756; RA Cohen I., Idan C., Rider P., Peleg R., Vornov E., Elena V., Tomas M., RA Martin T., Tudor C., Cicerone T., Wegner M., Mareike W., Brondani L., RA Lydia B., Freudenberg M., Marina F., Mittler G., Gerhard M., RA Ferrando-May E., Elisa F.M., Dinarello C.A., Apte R.N., Ron A.N., RA Schneider R., Robert S.; RT "IL-1alpha is a DNA damage sensor linking genotoxic stress signaling to RT sterile inflammation and innate immunity."; RL Sci. Rep. 5:14756-14756(2015). RN [24] RP SUBCELLULAR LOCATION, AND INTERACTION WITH TMED10. RX PubMed=32272059; DOI=10.1016/j.cell.2020.03.031; RA Zhang M., Liu L., Lin X., Wang Y., Li Y., Guo Q., Li S., Sun Y., Tao X., RA Zhang D., Lv X., Zheng L., Ge L.; RT "A Translocation Pathway for Vesicle-Mediated Unconventional Protein RT Secretion."; RL Cell 181:637-652(2020). RN [25] RP X-RAY CRYSTALLOGRAPHY. RX PubMed=2346741; DOI=10.1021/bi00463a009; RA Graves B.J., Hatada M.H., Hendrickson W.A., Miller J.K., Madison V.S., RA Satow Y.; RT "Structure of interleukin 1 alpha at 2.7-A resolution."; RL Biochemistry 29:2679-2684(1990). RN [26] {ECO:0007744|PDB:2L5X} RP STRUCTURE BY NMR OF 121-271, AND INTERACTION WITH S100A13. RX PubMed=21270123; DOI=10.1074/jbc.m110.201954; RA Mohan S.K., Yu C.; RT "The IL1alpha-S100A13 heterotetrameric complex structure: a component in RT the non-classical pathway for interleukin 1alpha secretion."; RL J. Biol. Chem. 286:14608-14617(2011). 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:26439902). After binding to its receptor IL1R1 together with CC its accessory protein IL1RAP, forms the high affinity interleukin-1 CC receptor complex (PubMed:17507369, PubMed:2950091). Signaling involves CC the recruitment of adapter molecules such as MYD88, IRAK1 or IRAK4 CC (PubMed:17507369). In turn, mediates the activation of NF-kappa-B and CC the three MAPK pathways p38, p42/p44 and JNK pathways CC (PubMed:14687581). Within the cell, acts as an alarmin and cell death CC results in its liberation in the extracellular space after disruption CC of the cell membrane to induce inflammation and alert the host to CC injury or damage (PubMed:15679580). In addition to its role as a danger CC signal, which occurs when the cytokine is passively released by cell CC necrosis, directly senses DNA damage and acts as a signal for genotoxic CC stress without loss of cell integrity (PubMed:26439902). CC {ECO:0000269|PubMed:14687581, ECO:0000269|PubMed:15679580, CC ECO:0000269|PubMed:17507369, ECO:0000269|PubMed:26439902, CC ECO:0000269|PubMed:2950091, ECO:0000269|PubMed:3258335}. 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 CC (PubMed:32272059). Interacts with IL1R1 (PubMed:2950091). Interacts CC with S100A13; this interaction is the first step in the export of IL1A, CC followed by direct translocation of this complex across the plasma CC membrane (PubMed:21270123). {ECO:0000269|PubMed:21270123, CC ECO:0000269|PubMed:2950091, ECO:0000269|PubMed:32272059}. CC -!- INTERACTION: CC P01583; P29466: CASP1; NbExp=3; IntAct=EBI-1749782, EBI-516667; CC P01583; PRO_0000004522 [P29466]: CASP1; NbExp=4; IntAct=EBI-1749782, EBI-1749839; CC P01583; O00165: HAX1; NbExp=3; IntAct=EBI-1749782, EBI-357001; CC P01583; P27930: IL1R2; NbExp=4; IntAct=EBI-1749782, EBI-2831568; CC P01583; O60684: KPNA6; NbExp=3; IntAct=EBI-1749782, EBI-359923; CC P01583; P50222: MEOX2; NbExp=3; IntAct=EBI-1749782, EBI-748397; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26439902}. Cytoplasm CC {ECO:0000269|PubMed:32272059}. Secreted {ECO:0000269|PubMed:26439902}. CC Note=The lack of a specific hydrophobic segment in the precursor CC sequence suggests that IL-1 is released by damaged cells or is secreted CC by a mechanism differing from that used for other secretory proteins. CC The secretion is dependent on protein unfolding and facilitated by the CC cargo receptor TMED10; it results in protein translocation from the CC cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate CC compartment) followed by vesicle entry and secretion (PubMed:32272059). CC Recruited to DNA damage sites and secreted after genotoxic stress. CC {ECO:0000269|PubMed:32272059}. 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:0000269|PubMed:26439902}. 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:0000269|PubMed:2115174}. 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:0000269|PubMed:3258335}. CC -!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-1 entry; CC URL="https://en.wikipedia.org/wiki/Interleukin_1"; 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; X02531; CAA26371.1; -; mRNA. DR EMBL; X03833; CAA27448.1; -; Genomic_DNA. DR EMBL; X02851; CAA26604.1; -; mRNA. DR EMBL; X56086; CAA39566.1; -; mRNA. DR EMBL; M28983; AAA59134.1; -; mRNA. DR EMBL; M15329; AAA59133.1; -; mRNA. DR EMBL; BN000002; CAD29871.1; -; Genomic_DNA. DR EMBL; BT007014; AAP35660.1; -; mRNA. DR EMBL; CR457414; CAG33695.1; -; mRNA. DR EMBL; AF536338; AAM96189.1; -; Genomic_DNA. DR EMBL; AK314850; BAG37367.1; -; mRNA. DR EMBL; AC112235; AAX93054.1; -; Genomic_DNA. DR EMBL; CH471217; EAW73604.1; -; Genomic_DNA. DR EMBL; BC013142; AAH13142.1; -; mRNA. DR CCDS; CCDS2101.1; -. DR PIR; A23385; ICHU1A. DR RefSeq; NP_000566.3; NM_000575.5. DR RefSeq; NP_001358483.1; NM_001371554.1. DR PDB; 2ILA; X-ray; 2.30 A; A=117-271. DR PDB; 2KKI; NMR; -; A=121-271. DR PDB; 2L5X; NMR; -; A/D=121-271. DR PDB; 5UC6; X-ray; 2.10 A; A=113-271. DR AlphaFoldDB; P01583; -. DR MDposit; P01583; -. DR SMR; P01583; -. DR BioGRID; 109768; 81. DR ComplexPortal; CPX-8830; Interleukin-1 alpha-soluble receptor type 1 complex. DR ComplexPortal; CPX-9166; Precursor interleukin-1 alpha-soluble receptor type 1 complex. DR ComplexPortal; CPX-9168; Interleukin-1 alpha decoy receptor-ligand type 2 complex. DR ComplexPortal; CPX-9169; Precursor interleukin-1 alpha-membrane-bound receptor type 1 complex. DR ComplexPortal; CPX-9173; Interleukin-1 alpha-membrane-bound receptor type 1 complex. DR DIP; DIP-40550N; -. DR FunCoup; P01583; 662. DR IntAct; P01583; 10. DR NDEx; IQUERY-CP-IL1A; 39 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000263339; -. DR BindingDB; P01583; -. DR ChEMBL; CHEMBL3580496; -. DR DrugBank; DB06372; Rilonacept. DR DrugCentral; P01583; -. DR MoonProt; P01583; -. DR TCDB; 1.A.109.1.1; the interleukin 1 (il1) family. DR GlyCosmos; P01583; 2 sites, No reported glycans. DR GlyGen; P01583; 2 sites. DR iPTMnet; P01583; -. DR PhosphoSitePlus; P01583; -. DR SwissPalm; P01583; -. DR BioMuta; IL1A; -. DR DMDM; 124297; -. DR MassIVE; P01583; -. DR PaxDb; 9606-ENSP00000263339; -. DR PeptideAtlas; P01583; -. DR ProteomicsDB; 51390; -. DR ABCD; P01583; 1 sequenced antibody. DR Antibodypedia; 3842; 1692 antibodies from 53 providers. DR CPTC; P01583; 3 antibodies. DR DNASU; 3552; -. DR Ensembl; ENST00000263339.4; ENSP00000263339.3; ENSG00000115008.7. DR Ensembl; ENST00000959423.1; ENSP00000629482.1; ENSG00000115008.7. DR GeneID; 3552; -. DR KEGG; hsa:3552; -. DR MANE-Select; ENST00000263339.4; ENSP00000263339.3; NM_000575.5; NP_000566.3. DR UCSC; uc002tig.4; human. DR AGR; HGNC:5991; -. DR ClinPGx; PA29807; -. DR CTD; 3552; -. DR DisGeNET; 3552; -. DR GeneCards; IL1A; -. DR HGNC; HGNC:5991; IL1A. DR HPA; ENSG00000115008; Tissue enhanced (esophagus, testis, urinary bladder). DR MIM; 147760; gene. DR OpenTargets; ENSG00000115008; -. DR VEuPathDB; HostDB:ENSG00000115008; -. DR eggNOG; ENOG502T3DD; Eukaryota. DR GeneTree; ENSGT00390000013353; -. DR HOGENOM; CLU_090014_0_0_1; -. DR InParanoid; P01583; -. DR OMA; ADLMSCY; -. DR OrthoDB; 9451248at2759; -. DR PAN-GO; P01583; 9 GO annotations based on evolutionary models. DR PhylomeDB; P01583; -. DR PathwayCommons; P01583; -. DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-HSA-448706; Interleukin-1 processing. DR Reactome; R-HSA-5620971; Pyroptosis. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-9020702; Interleukin-1 signaling. DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection. DR SignaLink; P01583; -. DR SIGNOR; P01583; -. DR Agora; ENSG00000115008; -. DR BioGRID-ORCS; 3552; 14 hits in 1152 CRISPR screens. DR ChiTaRS; IL1A; human. DR EvolutionaryTrace; P01583; -. DR GeneWiki; IL1A; -. DR GenomeRNAi; 3552; -. DR Pharos; P01583; Tchem. DR PRO; PR:P01583; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P01583; protein. DR Bgee; ENSG00000115008; Expressed in periodontal ligament and 112 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; EXP:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0045323; C:interleukin-1 receptor complex; NAS:ComplexPortal. DR GO; GO:0005634; C:nucleus; EXP:UniProtKB. DR GO; GO:0005886; C:plasma membrane; NAS:ComplexPortal. DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB. DR GO; GO:0005125; F:cytokine activity; IMP:BHF-UCL. DR GO; GO:0005149; F:interleukin-1 receptor binding; IEA:InterPro. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:BHF-UCL. DR GO; GO:0006955; P:immune response; IBA:GO_Central. DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central. DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; NAS:ComplexPortal. DR GO; GO:0030224; P:monocyte differentiation; NAS:ComplexPortal. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; TAS:BHF-UCL. DR GO; GO:0050728; P:negative regulation of inflammatory response; NAS:ComplexPortal. DR GO; GO:0032690; P:negative regulation of interleukin-1 alpha production; NAS:ComplexPortal. DR GO; GO:2000660; P:negative regulation of interleukin-1-mediated signaling pathway; NAS:ComplexPortal. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:BHF-UCL. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IBA:GO_Central. DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:0033092; P:positive regulation of immature T cell proliferation in thymus; IBA:GO_Central. DR GO; GO:0050729; P:positive regulation of inflammatory response; NAS:ComplexPortal. DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:BHF-UCL. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:ARUK-UCL. DR GO; GO:0043410; P:positive regulation of MAPK cascade; NAS:ComplexPortal. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:BHF-UCL. DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:AgBase. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:ARUK-UCL. DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISS:BHF-UCL. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IBA:GO_Central. DR GO; GO:0046688; P:response to copper ion; IDA: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 3D-structure; Acetylation; Cytokine; Cytoplasm; Direct protein sequencing; KW Glycoprotein; Inflammatory response; Lipoprotein; Mitogen; Myristate; KW Nucleus; Phosphoprotein; Proteomics identification; Pyrogen; KW Reference proteome; Secreted. FT PROPEP 1..112 FT /evidence="ECO:0000269|PubMed:3281727" FT /id="PRO_0000015265" FT CHAIN 113..271 FT /note="Interleukin-1 alpha" FT /id="PRO_0000015266" FT REGION 82..86 FT /note="Nuclear localization signal (NLS)" FT /evidence="ECO:0000269|PubMed:26439902" FT MOD_RES 82 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:26439902" FT MOD_RES 87 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P01582" FT LIPID 82 FT /note="N6-myristoyl lysine" FT /evidence="ECO:0000269|PubMed:8346241" FT LIPID 83 FT /note="N6-myristoyl lysine" FT /evidence="ECO:0000269|PubMed:8346241" 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" FT VARIANT 85 FT /note="R -> Q (in dbSNP:rs3783531)" FT /evidence="ECO:0000269|Ref.10" FT /id="VAR_014304" FT VARIANT 114 FT /note="A -> S (in dbSNP:rs17561)" FT /evidence="ECO:0000269|PubMed:2635664, FT ECO:0000269|PubMed:2994016, ECO:0000269|Ref.10" FT /id="VAR_014305" FT VARIANT 125 FT /note="N -> D (in dbSNP:rs17562)" FT /id="VAR_014600" FT VARIANT 138 FT /note="D -> N (in dbSNP:rs3783581)" FT /evidence="ECO:0000269|Ref.10" FT /id="VAR_014306" FT VARIANT 176 FT /note="D -> H (in dbSNP:rs1801715)" FT /id="VAR_014601" FT MUTAGEN 82 FT /note="K->Q: About 50% loss of cytokine secretion after DNA FT damage." FT /evidence="ECO:0000269|PubMed:26439902" FT STRAND 123..138 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 141..146 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 148..150 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 152..156 FT /evidence="ECO:0007829|PDB:5UC6" FT HELIX 160..162 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 166..175 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 176..178 FT /evidence="ECO:0007829|PDB:2KKI" FT STRAND 181..186 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 189..194 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 198..200 FT /evidence="ECO:0007829|PDB:2KKI" FT STRAND 203..206 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 212..215 FT /evidence="ECO:0007829|PDB:5UC6" FT HELIX 216..221 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 223..228 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 231..239 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 243..246 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 248..251 FT /evidence="ECO:0007829|PDB:2KKI" FT STRAND 253..257 FT /evidence="ECO:0007829|PDB:5UC6" FT STRAND 259..261 FT /evidence="ECO:0007829|PDB:2KKI" FT STRAND 264..267 FT /evidence="ECO:0007829|PDB:5UC6" SQ SEQUENCE 271 AA; 30607 MW; CBCCC49569D9ED40 CRC64; MAKVPDMFED LKNCYSENEE DSSSIDHLSL NQKSFYHVSY GPLHEGCMDQ SVSLSISETS KTSKLTFKES MVVVATNGKV LKKRRLSLSQ SITDDDLEAI ANDSEEEIIK PRSAPFSFLS NVKYNFMRII KYEFILNDAL NQSIIRANDQ YLTAAALHNL DEAVKFDMGA YKSSKDDAKI TVILRISKTQ LYVTAQDEDQ PVLLKEMPEI PKTITGSETN LLFFWETHGT KNYFTSVAHP NLFIATKQDY WVCLAGGPPS ITDFQILENQ A //