IL1A_HUMAN
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 03-AUG-2022, entry version 223.
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;
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;
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;
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 (2.7 ANGSTROMS).
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:2950091,PubMed:17507369). 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 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 -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il1a/";
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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_000575.4.
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 PDBsum; 2ILA; -.
DR PDBsum; 2KKI; -.
DR PDBsum; 2L5X; -.
DR PDBsum; 5UC6; -.
DR AlphaFoldDB; P01583; -.
DR SMR; P01583; -.
DR BioGRID; 109768; 27.
DR DIP; DIP-40550N; -.
DR IntAct; P01583; 6.
DR STRING; 9606.ENSP00000263339; -.
DR ChEMBL; CHEMBL3580496; -.
DR DrugBank; DB06372; Rilonacept.
DR DrugCentral; P01583; -.
DR TCDB; 1.A.109.1.1; the interleukin 1 (il1) family.
DR GlyGen; P01583; 2 sites.
DR iPTMnet; P01583; -.
DR PhosphoSitePlus; P01583; -.
DR SwissPalm; P01583; -.
DR BioMuta; IL1A; -.
DR DMDM; 124297; -.
DR EPD; P01583; -.
DR MassIVE; P01583; -.
DR PaxDb; P01583; -.
DR PeptideAtlas; P01583; -.
DR PRIDE; P01583; -.
DR ProteomicsDB; 51390; -.
DR ABCD; P01583; 2 sequenced antibodies.
DR Antibodypedia; 3842; 1536 antibodies from 45 providers.
DR CPTC; P01583; 3 antibodies.
DR DNASU; 3552; -.
DR Ensembl; ENST00000263339.4; ENSP00000263339.3; ENSG00000115008.6.
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 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 neXtProt; NX_P01583; -.
DR OpenTargets; ENSG00000115008; -.
DR PharmGKB; PA29807; -.
DR VEuPathDB; HostDB:ENSG00000115008; -.
DR eggNOG; ENOG502T3DD; Eukaryota.
DR GeneTree; ENSGT00390000013353; -.
DR HOGENOM; CLU_090014_0_0_1; -.
DR InParanoid; P01583; -.
DR OMA; SNMKYNF; -.
DR OrthoDB; 1513671at2759; -.
DR PhylomeDB; P01583; -.
DR TreeFam; TF300203; -.
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 BioGRID-ORCS; 3552; 14 hits in 1072 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 111 other tissues.
DR Genevisible; P01583; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
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:0006883; P:cellular sodium ion homeostasis; IEA:Ensembl.
DR GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IMP:BHF-UCL.
DR GO; GO:0035234; P:ectopic germ cell programmed cell death; IEA:Ensembl.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0001660; P:fever generation; IEA:UniProtKB-KW.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:1904445; P:negative regulation of establishment of Sertoli cell barrier; IEA:Ensembl.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; TAS:BHF-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:BHF-UCL.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
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:BHF-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:ARUK-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:BHF-UCL.
DR GO; GO:1902624; P:positive regulation of neutrophil migration; IEA:Ensembl.
DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; IEA:Ensembl.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:AgBase.
DR GO; GO:0010893; P:positive regulation of steroid biosynthetic process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
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:0032956; P:regulation of actin cytoskeleton organization; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0046688; P:response to copper ion; IDA:UniProtKB.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0033591; P:response to L-ascorbic acid; IEA:Ensembl.
DR GO; GO:0010243; P:response to organonitrogen compound; IEA:Ensembl.
DR GO; GO:0010193; P:response to ozone; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytokine; Cytoplasm; Direct protein sequencing;
KW Glycoprotein; Inflammatory response; Lipoprotein; Mitogen; Myristate;
KW Nucleus; Phosphoprotein; Pyrogen; 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 143..146
FT /evidence="ECO:0007829|PDB:5UC6"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:5UC6"
FT STRAND 152..155
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
