ID HMGB1_HUMAN Reviewed; 215 AA.
AC P09429; A5D8W9; Q14321; Q5T7C3; Q6IBE1;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 28-JUN-2023, entry version 236.
DE RecName: Full=High mobility group protein B1;
DE AltName: Full=High mobility group protein 1;
DE Short=HMG-1;
GN Name=HMGB1 {ECO:0000312|HGNC:HGNC:4983}; Synonyms=HMG1;
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=2922262; DOI=10.1093/nar/17.3.1197;
RA Wen L., Huang J.K., Johnson B.H., Reeck G.R.;
RT "A human placental cDNA clone that encodes nonhistone chromosomal protein
RT HMG-1.";
RL Nucleic Acids Res. 17:1197-1214(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8661151; DOI=10.1006/geno.1996.0369;
RA Ferrari S., Finelli P., Rocchi M., Bianchi M.E.;
RT "The active gene that encodes human high mobility group 1 protein (HMG1)
RT contains introns and maps to chromosome 13.";
RL Genomics 35:367-371(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ARG-11; GLU-149 AND GLY-190.
RX PubMed=9036861;
RX DOI=10.1002/(sici)1097-0215(19970220)74:1<1::aid-ijc1>3.0.co;2-6;
RA Xiang Y.-Y., Wang D.-Y., Tanaka M., Suzuki M., Kiyokawa E., Igarashi H.,
RA Niato Y., Shen Q., Sugimura H.;
RT "Expression of high-mobility group-1 mRNA in human gastrointestinal
RT adenocarcinoma and corresponding non-cancerous mucosa.";
RL Int. J. Cancer 74:1-6(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=17610420; DOI=10.1111/j.1399-0039.2007.00854.x;
RA Kornblit B., Munthe-Fog L., Petersen S., Madsen H., Vindeloev L.,
RA Garred P.;
RT "The genetic variation of the human HMGB1 gene.";
RL Tissue Antigens 70:151-156(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA He F.T., Yang Z.H., Ji Q., Li R., Peng J., Jiang Y., Zhong X.;
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Small intestine;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
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 [9]
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 (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-156.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Cervix, and Testis;
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 [14]
RP PROTEIN SEQUENCE OF 58-65 AND 113-127.
RC TISSUE=Mammary carcinoma;
RX PubMed=9150946; DOI=10.1002/elps.1150180342;
RA Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E., Simpson R.J.,
RA Dorow D.S.;
RT "Two-dimensional electrophoretic analysis of human breast carcinoma
RT proteins: mapping of proteins that bind to the SH3 domain of mixed lineage
RT kinase MLK2.";
RL Electrophoresis 18:588-598(1997).
RN [15]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11154118;
RA Rouhiainen A., Imai S., Rauvala H., Parkkinen J.;
RT "Occurrence of amphoterin (HMG1) as an endogenous protein of human
RT platelets that is exported to the cell surface upon platelet activation.";
RL Thromb. Haemost. 84:1087-1094(2000).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=12231511; DOI=10.1093/embo-reports/kvf198;
RA Gardella S., Andrei C., Ferrera D., Lotti L.V., Torrisi M.R., Bianchi M.E.,
RA Rubartelli A.;
RT "The nuclear protein HMGB1 is secreted by monocytes via a non-classical,
RT vesicle-mediated secretory pathway.";
RL EMBO Rep. 3:995-1001(2002).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=14532127; DOI=10.1093/emboj/cdg516;
RA Bonaldi T., Talamo F., Scaffidi P., Ferrera D., Porto A., Bachi A.,
RA Rubartelli A., Agresti A., Bianchi M.E.;
RT "Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it
RT towards secretion.";
RL EMBO J. 22:5551-5560(2003).
RN [18]
RP FUNCTION, AND DOMAIN.
RX PubMed=12765338; DOI=10.1007/bf03402105;
RA Li J., Kokkola R., Tabibzadeh S., Yang R., Ochani M., Qiang X.,
RA Harris H.E., Czura C.J., Wang H., Ulloa L., Wang H., Warren H.S.,
RA Moldawer L.L., Fink M.P., Andersson U., Tracey K.J., Yang H.;
RT "Structural basis for the proinflammatory cytokine activity of high
RT mobility group box 1.";
RL Mol. Med. 9:37-45(2003).
RN [19]
RP FUNCTION, AND INTERACTION WITH MSH2.
RX PubMed=15014079; DOI=10.1074/jbc.m401931200;
RA Yuan F., Gu L., Guo S., Wang C., Li G.M.;
RT "Evidence for involvement of HMGB1 protein in human DNA mismatch repair.";
RL J. Biol. Chem. 279:20935-20940(2004).
RN [20]
RP INVOLVEMENT IN INFLAMMATORY DISEASES.
RX PubMed=14695889; DOI=10.1073/pnas.2434651100;
RA Yang H., Ochani M., Li J., Qiang X., Tanovic M., Harris H.E., Susarla S.M.,
RA Ulloa L., Wang H., DiRaimo R., Czura C.J., Wang H., Roth J., Warren H.S.,
RA Fink M.P., Fenton M.J., Andersson U., Tracey K.J.;
RT "Reversing established sepsis with antagonists of endogenous high-mobility
RT group box 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:296-301(2004).
RN [21]
RP FUNCTION.
RX PubMed=16143102; DOI=10.1016/j.cell.2005.06.027;
RA Zhang Y., Yuan F., Presnell S.R., Tian K., Gao Y., Tomkinson A.E., Gu L.,
RA Li G.-M.;
RT "Reconstitution of 5'-directed human mismatch repair in a purified
RT system.";
RL Cell 122:693-705(2005).
RN [22]
RP INTERACTION WITH THBD.
RX PubMed=15841214; DOI=10.1172/jci22782;
RA Abeyama K., Stern D.M., Ito Y., Kawahara K., Yoshimoto Y., Tanaka M.,
RA Uchimura T., Ida N., Yamazaki Y., Yamada S., Yamamoto Y., Yamamoto H.,
RA Iino S., Taniguchi N., Maruyama I.;
RT "The N-terminal domain of thrombomodulin sequesters high-mobility group-B1
RT protein, a novel antiinflammatory mechanism.";
RL J. Clin. Invest. 115:1267-1274(2005).
RN [23]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15944249; DOI=10.4049/jimmunol.174.12.7506;
RA Dumitriu I.E., Baruah P., Valentinis B., Voll R.E., Herrmann M.,
RA Nawroth P.P., Arnold B., Bianchi M.E., Manfredi A.A., Rovere-Querini P.;
RT "Release of high mobility group box 1 by dendritic cells controls T cell
RT activation via the receptor for advanced glycation end products.";
RL J. Immunol. 174:7506-7515(2005).
RN [24]
RP FUNCTION.
RX PubMed=15607795; DOI=10.1016/j.molimm.2004.07.023;
RA DeMarco R.A., Fink M.P., Lotze M.T.;
RT "Monocytes promote natural killer cell interferon gamma production in
RT response to the endogenous danger signal HMGB1.";
RL Mol. Immunol. 42:433-444(2005).
RN [25]
RP SUBCELLULAR LOCATION.
RX PubMed=16855214; DOI=10.1152/ajpcell.00616.2005;
RA Bell C.W., Jiang W., Reich C.F., Pisetsky D.S.;
RT "The extracellular release of HMGB1 during apoptotic cell death.";
RL Am. J. Physiol. 291:C1318-C1325(2006).
RN [26]
RP DISULFIDE BRIDGE, AND REDOX FORMS.
RX PubMed=16962095; DOI=10.1016/j.yexcr.2006.07.020;
RA Hoppe G., Talcott K.E., Bhattacharya S.K., Crabb J.W., Sears J.E.;
RT "Molecular basis for the redox control of nuclear transport of the
RT structural chromatin protein Hmgb1.";
RL Exp. Cell Res. 312:3526-3538(2006).
RN [27]
RP PHOSPHORYLATION, MUTAGENESIS OF SER-35; SER-39; SER-42; SER-46; SER-53 AND
RP SER-181, SUBCELLULAR LOCATION, AND INTERACTION WITH KPNA1.
RX PubMed=17114460; DOI=10.4049/jimmunol.177.11.7889;
RA Youn J.H., Shin J.S.;
RT "Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that
RT redirects it toward secretion.";
RL J. Immunol. 177:7889-7897(2006).
RN [28]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-106.
RX PubMed=18631454; DOI=10.1016/j.immuni.2008.05.013;
RA Kazama H., Ricci J.E., Herndon J.M., Hoppe G., Green D.R., Ferguson T.A.;
RT "Induction of immunological tolerance by apoptotic cells requires caspase-
RT dependent oxidation of high-mobility group box-1 protein.";
RL Immunity 29:21-32(2008).
RN [29]
RP FUNCTION.
RX PubMed=17803946; DOI=10.1016/j.molcel.2007.06.029;
RA Prasad R., Liu Y., Deterding L.J., Poltoratsky V.P., Kedar P.S.,
RA Horton J.K., Kanno S., Asagoshi K., Hou E.W., Khodyreva S.N., Lavrik O.I.,
RA Tomer K.B., Yasui A., Wilson S.H.;
RT "HMGB1 is a cofactor in mammalian base excision repair.";
RL Mol. Cell 27:829-841(2007).
RN [30]
RP FUNCTION, TISSUE SPECIFICITY, AND INVOLVEMENT IN AUTOIMMUNE DISEASES.
RX PubMed=19064698; DOI=10.1084/jem.20081165;
RA Urbonaviciute V., Furnrohr B.G., Meister S., Munoz L., Heyder P.,
RA De Marchis F., Bianchi M.E., Kirschning C., Wagner H., Manfredi A.A.,
RA Kalden J.R., Schett G., Rovere-Querini P., Herrmann M., Voll R.E.;
RT "Induction of inflammatory and immune responses by HMGB1-nucleosome
RT complexes: implications for the pathogenesis of SLE.";
RL J. Exp. Med. 205:3007-3018(2008).
RN [31]
RP FUNCTION, AND INTERACTION WITH IL1B.
RX PubMed=18250463; DOI=10.4049/jimmunol.180.4.2531;
RA Sha Y., Zmijewski J., Xu Z., Abraham E.;
RT "HMGB1 develops enhanced proinflammatory activity by binding to
RT cytokines.";
RL J. Immunol. 180:2531-2537(2008).
RN [32]
RP FUNCTION.
RX PubMed=18354232; DOI=10.4049/jimmunol.180.7.5067;
RA Youn J.H., Oh Y.J., Kim E.S., Choi J.E., Shin J.S.;
RT "High mobility group box 1 protein binding to lipopolysaccharide
RT facilitates transfer of lipopolysaccharide to CD14 and enhances
RT lipopolysaccharide-mediated TNF-alpha production in human monocytes.";
RL J. Immunol. 180:5067-5074(2008).
RN [33]
RP INTERACTION WITH HNF1A.
RX PubMed=18160415; DOI=10.1093/nar/gkm1131;
RA Yu M., Wang J., Li W., Yuan Y.Z., Li C.Y., Qian X.H., Xu W.X., Zhan Y.Q.,
RA Yang X.M.;
RT "Proteomic screen defines the hepatocyte nuclear factor 1alpha-binding
RT partners and identifies HMGB1 as a new cofactor of HNF1alpha.";
RL Nucleic Acids Res. 36:1209-1219(2008).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 AND SER-100, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [35]
RP REDOX FORMS, AND SUBCELLULAR LOCATION.
RX PubMed=19811284; DOI=10.1080/08916930902831803;
RA Urbonaviciute V., Meister S., Furnrohr B.G., Frey B., Guckel E., Schett G.,
RA Herrmann M., Voll R.E.;
RT "Oxidation of the alarmin high-mobility group box 1 protein (HMGB1) during
RT apoptosis.";
RL Autoimmunity 42:305-307(2009).
RN [36]
RP FUNCTION, AND INTERACTION WITH XPA AND XPC.
RX PubMed=19446504; DOI=10.1016/j.dnarep.2009.04.001;
RA Lange S.S., Reddy M.C., Vasquez K.M.;
RT "Human HMGB1 directly facilitates interactions between nucleotide excision
RT repair proteins on triplex-directed psoralen interstrand crosslinks.";
RL DNA Repair 8:865-872(2009).
RN [37]
RP REVIEW ON FUNCTION RELATED TO DNA REPAIR.
RX PubMed=19360789; DOI=10.1002/mc.20544;
RA Lange S.S., Vasquez K.M.;
RT "HMGB1: the jack-of-all-trades protein is a master DNA repair mechanic.";
RL Mol. Carcinog. 48:571-580(2009).
RN [38]
RP FUNCTION, INTERACTION WITH CD24, AND LIGAND FOR CD24:SIGLEC10 RECEPTOR
RP COMPLEX.
RX PubMed=19264983; DOI=10.1126/science.1168988;
RA Chen G.Y., Tang J., Zheng P., Liu Y.;
RT "CD24 and Siglec-10 selectively repress tissue damage-induced immune
RT responses.";
RL Science 323:1722-1725(2009).
RN [39]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-30, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [40]
RP REVIEW ON FUNCTION RELATED TO DNA-BINDING.
RX PubMed=20123072; DOI=10.1016/j.bbagrm.2009.09.008;
RA Stros M.;
RT "HMGB proteins: interactions with DNA and chromatin.";
RL Biochim. Biophys. Acta 1799:101-113(2010).
RN [41]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BECN1.
RX PubMed=20819940; DOI=10.1083/jcb.200911078;
RA Tang D., Kang R., Livesey K.M., Cheh C.W., Farkas A., Loughran P.,
RA Hoppe G., Bianchi M.E., Tracey K.J., Zeh H.J. III, Lotze M.T.;
RT "Endogenous HMGB1 regulates autophagy.";
RL J. Cell Biol. 190:881-892(2010).
RN [42]
RP FUNCTION, LIGAND FOR TLR4:LY96 RECEPTOR COMPLEX, AND DOMAIN.
RX PubMed=20547845; DOI=10.1073/pnas.1003893107;
RA Yang H., Hreggvidsdottir H.S., Palmblad K., Wang H., Ochani M., Li J.,
RA Lu B., Chavan S., Rosas-Ballina M., Al-Abed Y., Akira S., Bierhaus A.,
RA Erlandsson-Harris H., Andersson U., Tracey K.J.;
RT "A critical cysteine is required for HMGB1 binding to Toll-like receptor 4
RT and activation of macrophage cytokine release.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11942-11947(2010).
RN [43]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [44]
RP FUNCTION.
RX PubMed=21395369; DOI=10.1089/ars.2010.3666;
RA Tang D., Kang R., Livesey K.M., Zeh H.J., Lotze M.T.;
RT "High mobility group box 1 (HMGB1) activates an autophagic response to
RT oxidative stress.";
RL Antioxid. Redox Signal. 15:2185-2195(2011).
RN [45]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [46]
RP LPS-BINDING.
RX PubMed=21660935; DOI=10.1002/eji.201141391;
RA Youn J.H., Kwak M.S., Wu J., Kim E.S., Ji Y., Min H.J., Yoo J.H.,
RA Choi J.E., Cho H.S., Shin J.S.;
RT "Identification of lipopolysaccharide-binding peptide regions within HMGB1
RT and their effects on subclinical endotoxemia in a mouse model.";
RL Eur. J. Immunol. 41:2753-2762(2011).
RN [47]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [48]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH INFLUENZA A VIRUS PROTEIN
RP NP (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=22696656; DOI=10.1128/jvi.00789-12;
RA Moisy D., Avilov S.V., Jacob Y., Laoide B.M., Ge X., Baudin F., Naffakh N.,
RA Jestin J.L.;
RT "HMGB1 protein binds to influenza virus nucleoprotein and promotes viral
RT replication.";
RL J. Virol. 86:9122-9133(2012).
RN [49]
RP FUNCTION.
RX PubMed=22473704; DOI=10.1093/intimm/dxs051;
RA Wild C.A., Bergmann C., Fritz G., Schuler P., Hoffmann T.K., Lotfi R.,
RA Westendorf A., Brandau S., Lang S.;
RT "HMGB1 conveys immunosuppressive characteristics on regulatory and
RT conventional T cells.";
RL Int. Immunol. 24:485-494(2012).
RN [50]
RP FUNCTION, AND INTERACTION WITH CXCL12.
RX PubMed=22370717; DOI=10.1084/jem.20111739;
RA Schiraldi M., Raucci A., Munoz L.M., Livoti E., Celona B., Venereau E.,
RA Apuzzo T., De Marchis F., Pedotti M., Bachi A., Thelen M., Varani L.,
RA Mellado M., Proudfoot A., Bianchi M.E., Uguccioni M.;
RT "HMGB1 promotes recruitment of inflammatory cells to damaged tissues by
RT forming a complex with CXCL12 and signaling via CXCR4.";
RL J. Exp. Med. 209:551-563(2012).
RN [51]
RP REDOX FORMS, AND SUBCELLULAR LOCATION.
RX PubMed=22869893; DOI=10.1084/jem.20120189;
RA Venereau E., Casalgrandi M., Schiraldi M., Antoine D.J., Cattaneo A.,
RA De Marchis F., Liu J., Antonelli A., Preti A., Raeli L., Shams S.S.,
RA Yang H., Varani L., Andersson U., Tracey K.J., Bachi A., Uguccioni M.,
RA Bianchi M.E.;
RT "Mutually exclusive redox forms of HMGB1 promote cell recruitment or
RT proinflammatory cytokine release.";
RL J. Exp. Med. 209:1519-1528(2012).
RN [52]
RP ACETYLATION.
RX PubMed=22801494; DOI=10.1038/nature11290;
RA Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P.,
RA Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y.,
RA Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U.,
RA Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J.;
RT "Novel role of PKR in inflammasome activation and HMGB1 release.";
RL Nature 488:670-674(2012).
RN [53]
RP INVOLVEMENT IN CANCER THERAPY.
RX PubMed=23040637; DOI=10.1016/j.ejca.2012.09.016;
RA Luo Y., Chihara Y., Fujimoto K., Sasahira T., Kuwada M., Fujiwara R.,
RA Fujii K., Ohmori H., Kuniyasu H.;
RT "High mobility group box 1 released from necrotic cells enhances regrowth
RT and metastasis of cancer cells that have survived chemotherapy.";
RL Eur. J. Cancer 49:741-751(2013).
RN [54]
RP REVIEW ON FUNCTION RELATED TO ADAPTIVE IMMUNITY.
RX PubMed=23519706; DOI=10.3389/fimmu.2013.00068;
RA Li G., Liang X., Lotze M.T.;
RT "HMGB1: The central cytokine for all lymphoid cells.";
RL Front. Immunol. 4:68-68(2013).
RN [55]
RP FUNCTION, AND INTERACTION WITH HTT.
RX PubMed=23303669; DOI=10.4049/jimmunol.1202472;
RA Min H.J., Ko E.A., Wu J., Kim E.S., Kwon M.K., Kwak M.S., Choi J.E.,
RA Lee J.E., Shin J.S.;
RT "Chaperone-like activity of high-mobility group box 1 protein and its role
RT in reducing the formation of polyglutamine aggregates.";
RL J. Immunol. 190:1797-1806(2013).
RN [56]
RP REVIEW ON FUNCTION RELATED TO INFLAMMATION.
RX PubMed=23446148; DOI=10.1189/jlb.1212662;
RA Yang H., Antoine D.J., Andersson U., Tracey K.J.;
RT "The many faces of HMGB1: molecular structure-functional activity in
RT inflammation, apoptosis, and chemotaxis.";
RL J. Leukoc. Biol. 93:865-873(2013).
RN [57]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [58]
RP REVIEW.
RX PubMed=23994764; DOI=10.1016/j.semcancer.2013.08.002;
RA Li G., Tang D., Lotze M.T.;
RT "Menage a Trois in stress: DAMPs, redox and autophagy.";
RL Semin. Cancer Biol. 23:380-390(2013).
RN [59]
RP FUNCTION.
RX PubMed=24971542; DOI=10.1016/j.bbrc.2014.06.074;
RA Liu L., Yang M., Kang R., Dai Y., Yu Y., Gao F., Wang H., Sun X., Li X.,
RA Li J., Wang H., Cao L., Tang D.;
RT "HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation
RT through RAGE.";
RL Biochem. Biophys. Res. Commun. 450:851-856(2014).
RN [60]
RP FUNCTION, MUTAGENESIS OF ASP-67, INTERACTION WITH AGER, DOMAIN, AND
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=24474694; DOI=10.1074/jbc.m113.541474;
RA LeBlanc P.M., Doggett T.A., Choi J., Hancock M.A., Durocher Y., Frank F.,
RA Nagar B., Ferguson T.A., Saleh M.;
RT "An immunogenic peptide in the A-box of HMGB1 protein reverses apoptosis-
RT induced tolerance through RAGE receptor.";
RL J. Biol. Chem. 289:7777-7786(2014).
RN [61]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [62]
RP NOMENCLATURE OF REDOX FORMS.
RX PubMed=24531895; DOI=10.2119/molmed.2014.00022;
RA Antoine D.J., Harris H.E., Andersson U., Tracey K.J., Bianchi M.E.;
RT "A systematic nomenclature for the redox states of high mobility group box
RT (HMGB) proteins.";
RL Mol. Med. 20:135-137(2014).
RN [63]
RP REVIEW ON INVOLVEMENT IN DISEASES AND THERAPEUTIC TARGET.
RX PubMed=24220159; DOI=10.1016/j.pharmthera.2013.11.001;
RA Musumeci D., Roviello G.N., Montesarchio D.;
RT "An overview on HMGB1 inhibitors as potential therapeutic agents in HMGB1-
RT related pathologies.";
RL Pharmacol. Ther. 141:347-357(2014).
RN [64]
RP FUNCTION.
RX PubMed=25549101; DOI=10.1371/journal.pone.0115809;
RA Lee L.C., Chen C.M., Wang P.R., Su M.T., Lee-Chen G.J., Chang C.Y.;
RT "Role of high mobility group box 1 (HMGB1) in SCA17 pathogenesis.";
RL PLoS ONE 9:E115809-E115809(2014).
RN [65]
RP REVIEW ON FUNCTION RELATED TO INNATE IMMUNITY.
RX PubMed=25048472; DOI=10.3349/ymj.2014.55.5.1165;
RA Lee S.A., Kwak M.S., Kim S., Shin J.S.;
RT "The role of high mobility group box 1 in innate immunity.";
RL Yonsei Med. J. 55:1165-1176(2014).
RN [66]
RP INVOLVEMENT AUTOIMMUNE DISEASES.
RX PubMed=26078984; DOI=10.1155/2015/946748;
RA Lu M., Yu S., Xu W., Gao B., Xiong S.;
RT "HMGB1 promotes systemic lupus erythematosus by enhancing macrophage
RT inflammatory response.";
RL J. Immunol. Res. 2015:946748-946748(2015).
RN [67]
RP FUNCTION.
RX PubMed=25660311; DOI=10.1159/000369972;
RA Kwak M.S., Lim M., Lee Y.J., Lee H.S., Kim Y.H., Youn J.H., Choi J.E.,
RA Shin J.S.;
RT "HMGB1 binds to lipoteichoic acid and enhances TNF-alpha and IL-6
RT production through HMGB1-mediated transfer of lipoteichoic acid to CD14 and
RT TLR2.";
RL J. Innate Immun. 7:405-416(2015).
RN [68]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [69]
RP FUNCTION, INTERACTION WITH ADENOVIRUS PROTEIN PVII (MICROBIAL INFECTION),
RP AND SUBCELLULAR LOCATION.
RX PubMed=27362237; DOI=10.1038/nature18317;
RA Avgousti D.C., Herrmann C., Kulej K., Pancholi N.J., Sekulic N.,
RA Petrescu J., Molden R.C., Blumenthal D., Paris A.J., Reyes E.D.,
RA Ostapchuk P., Hearing P., Seeholzer S.H., Worthen G.S., Black B.E.,
RA Garcia B.A., Weitzman M.D.;
RT "A core viral protein binds host nucleosomes to sequester immune danger
RT signals.";
RL Nature 535:173-177(2016).
RN [70]
RP ADP-RIBOSYLATION AT SER-181.
RX PubMed=28190768; DOI=10.1016/j.molcel.2017.01.003;
RA Bonfiglio J.J., Fontana P., Zhang Q., Colby T., Gibbs-Seymour I.,
RA Atanassov I., Bartlett E., Zaja R., Ahel I., Matic I.;
RT "Serine ADP-ribosylation depends on HPF1.";
RL Mol. Cell 0:0-0(2017).
RN [71]
RP SUBCELLULAR LOCATION, AND TRANSGLUTAMINATION AT LYS-28; LYS-43; LYS-44;
RP LYS-68; LYS-177; LYS-180; LYS-182; LYS-183 AND LYS-184.
RX PubMed=29618516; DOI=10.1074/jbc.ra117.001078;
RA Willis W.L., Wang L., Wada T.T., Gardner M., Abdouni O., Hampton J.,
RA Valiente G., Young N., Ardoin S., Agarwal S., Freitas M.A., Wu L.C.,
RA Jarjour W.N.;
RT "The proinflammatory protein HMGB1 is a substrate of transglutaminase-2 and
RT forms high-molecular weight complexes with autoantigens.";
RL J. Biol. Chem. 293:8394-8409(2018).
RN [72]
RP FUNCTION, FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, AND
RP INDUCTION BY SARS-COV2 (MICROBIAL INFECTION).
RX PubMed=33147444; DOI=10.1016/j.cell.2020.10.028;
RA Wei J., Alfajaro M.M., DeWeirdt P.C., Hanna R.E., Lu-Culligan W.J.,
RA Cai W.L., Strine M.S., Zhang S.M., Graziano V.R., Schmitz C.O., Chen J.S.,
RA Mankowski M.C., Filler R.B., Ravindra N.G., Gasque V., de Miguel F.J.,
RA Patil A., Chen H., Oguntuyo K.Y., Abriola L., Surovtseva Y.V.,
RA Orchard R.C., Lee B., Lindenbach B.D., Politi K., van Dijk D., Kadoch C.,
RA Simon M.D., Yan Q., Doench J.G., Wilen C.B.;
RT "Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2
RT Infection.";
RL Cell 184:76-91.e13(2021).
RN [73]
RP FUNCTION, AND INTERACTION WITH AGER.
RX PubMed=34743181; DOI=10.1038/s41420-021-00729-0;
RA Wang G., Jin S., Huang W., Li Y., Wang J., Ling X., Huang Y., Hu Y., Li C.,
RA Meng Y., Li X.;
RT "LPS-induced macrophage HMGB1-loaded extracellular vesicles trigger
RT hepatocyte pyroptosis by activating the NLRP3 inflammasome.";
RL Cell. Death. Discov. 7:337-337(2021).
RN [74]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=34922257; DOI=10.1016/j.virol.2021.12.002;
RA Reinhart N.M., Akinyemi I.A., Frey T.R., Xu H., Agudelo C., Brathwaite J.,
RA Burton E.M., Burgula S., McIntosh M.T., Bhaduri-McIntosh S.;
RT "The danger molecule HMGB1 cooperates with the NLRP3 inflammasome to
RT sustain expression of the EBV lytic switch protein in Burkitt lymphoma
RT cells.";
RL Virology 566:136-142(2022).
RN [75]
RP FUNCTION (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=34971702; DOI=10.1016/j.virusres.2021.198668;
RA Chaudhary N., Srivastava S., Dave U., Ojha A., Guchhait P., Chandele A.,
RA Patel A.K.;
RT "High-mobility group box 1 protein promotes dengue virus replication by
RT interacting with untranslated regions of viral genome.";
RL Virus Res. 309:198668-198668(2022).
RN [76]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH SARS-COV-2 ORF3A, AND
RP SUBCELLULAR LOCATION (MICROBIAL INFECTION).
RX PubMed=35239449; DOI=10.1080/15548627.2022.2039992;
RA Zhang X., Yang Z., Pan T., Long X., Sun Q., Wang P.H., Li X., Kuang E.;
RT "SARS-CoV-2 ORF3a induces RETREG1/FAM134B-dependent reticulophagy and
RT triggers sequential ER stress and inflammatory responses during SARS-CoV-2
RT infection.";
RL Autophagy 0:0-0(2022).
RN [77]
RP STRUCTURE BY NMR OF 1-166.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the tandem HMG box domain from human high mobility
RT group protein B1.";
RL Submitted (FEB-2008) to the PDB data bank.
RN [78]
RP STRUCTURE BY NMR OF 2-84 IN COMPLEX WITH TP53, FUNCTION, AND DOMAIN.
RX PubMed=23063560; DOI=10.1016/j.str.2012.09.004;
RA Rowell J.P., Simpson K.L., Stott K., Watson M., Thomas J.O.;
RT "HMGB1-facilitated p53 DNA binding occurs via HMG-Box/p53 transactivation
RT domain interaction, regulated by the acidic tail.";
RL Structure 20:2014-2024(2012).
RN [79]
RP STRUCTURE BY NMR OF 1-84.
RX PubMed=24427810; DOI=10.1016/j.bbrc.2013.10.085;
RA Wang J., Tochio N., Takeuchi A., Uewaki J., Kobayashi N., Tate S.;
RT "Redox-sensitive structural change in the A-domain of HMGB1 and its
RT implication for the binding to cisplatin modified DNA.";
RL Biochem. Biophys. Res. Commun. 441:701-706(2013).
CC -!- FUNCTION: Multifunctional redox sensitive protein with various roles in
CC different cellular compartments. In the nucleus is one of the major
CC chromatin-associated non-histone proteins and acts as a DNA chaperone
CC involved in replication, transcription, chromatin remodeling, V(D)J
CC recombination, DNA repair and genome stability (PubMed:33147444).
CC Proposed to be an universal biosensor for nucleic acids. Promotes host
CC inflammatory response to sterile and infectious signals and is involved
CC in the coordination and integration of innate and adaptive immune
CC responses. In the cytoplasm functions as sensor and/or chaperone for
CC immunogenic nucleic acids implicating the activation of TLR9-mediated
CC immune responses, and mediates autophagy. Acts as danger associated
CC molecular pattern (DAMP) molecule that amplifies immune responses
CC during tissue injury (PubMed:27362237). Released to the extracellular
CC environment can bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform
CC 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and
CC activates cells through engagement of multiple surface receptors
CC (PubMed:34743181). In the extracellular compartment fully reduced HMGB1
CC (released by necrosis) acts as a chemokine, disulfide HMGB1 (actively
CC secreted) as a cytokine, and sulfonyl HMGB1 (released from apoptotic
CC cells) promotes immunological tolerance (PubMed:23519706,
CC PubMed:23446148, PubMed:23994764, PubMed:25048472). Has proangiogdenic
CC activity (By similarity). May be involved in platelet activation (By
CC similarity). Binds to phosphatidylserine and phosphatidylethanolamide
CC (By similarity). Bound to RAGE mediates signaling for neuronal
CC outgrowth (By similarity). May play a role in accumulation of expanded
CC polyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP
CC (PubMed:23303669, PubMed:25549101). {ECO:0000250|UniProtKB:P10103,
CC ECO:0000250|UniProtKB:P12682, ECO:0000250|UniProtKB:P63158,
CC ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:23303669,
CC ECO:0000269|PubMed:25549101, ECO:0000269|PubMed:27362237,
CC ECO:0000269|PubMed:33147444, ECO:0000269|PubMed:34743181,
CC ECO:0000305|PubMed:23446148, ECO:0000305|PubMed:23519706,
CC ECO:0000305|PubMed:23994764, ECO:0000305|PubMed:25048472}.
CC -!- FUNCTION: Nuclear functions are attributed to fully reduced HGMB1.
CC Associates with chromatin and binds DNA with a preference to non-
CC canonical DNA structures such as single-stranded DNA, DNA-containing
CC cruciforms or bent structures, supercoiled DNA and ZDNA. Can bent DNA
CC and enhance DNA flexibility by looping thus providing a mechanism to
CC promote activities on various gene promoters by enhancing transcription
CC factor binding and/or bringing distant regulatory sequences into close
CC proximity (PubMed:20123072). May have an enhancing role in nucleotide
CC excision repair (NER) (By similarity). However, effects in NER using in
CC vitro systems have been reported conflictingly (PubMed:19446504,
CC PubMed:19360789). May be involved in mismatch repair (MMR) and base
CC excision repair (BER) pathways (PubMed:15014079, PubMed:16143102,
CC PubMed:17803946). May be involved in double strand break repair such as
CC non-homologous end joining (NHEJ) (By similarity). Involved in V(D)J
CC recombination by acting as a cofactor of the RAG complex: acts by
CC stimulating cleavage and RAG protein binding at the 23 bp spacer of
CC conserved recombination signal sequences (RSS) (By similarity). In
CC vitro can displace histone H1 from highly bent DNA (By similarity). Can
CC restructure the canonical nucleosome leading to relaxation of
CC structural constraints for transcription factor-binding (By
CC similarity). Enhances binding of sterol regulatory element-binding
CC proteins (SREBPs) such as SREBF1 to their cognate DNA sequences and
CC increases their transcriptional activities (By similarity). Facilitates
CC binding of TP53 to DNA (PubMed:23063560). Proposed to be involved in
CC mitochondrial quality control and autophagy in a transcription-
CC dependent fashion implicating HSPB1; however, this function has been
CC questioned (By similarity). Can modulate the activity of the telomerase
CC complex and may be involved in telomere maintenance (By similarity).
CC {ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63158,
CC ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:15014079,
CC ECO:0000269|PubMed:16143102, ECO:0000269|PubMed:17803946,
CC ECO:0000269|PubMed:19446504, ECO:0000269|PubMed:23063560,
CC ECO:0000305|PubMed:19360789, ECO:0000305|PubMed:20123072}.
CC -!- FUNCTION: In the cytoplasm proposed to dissociate the BECN1:BCL2
CC complex via competitive interaction with BECN1 leading to autophagy
CC activation (PubMed:20819940). Involved in oxidative stress-mediated
CC autophagy (PubMed:21395369). Can protect BECN1 and ATG5 from calpain-
CC mediated cleavage and thus proposed to control their proautophagic and
CC proapoptotic functions and to regulate the extent and severity of
CC inflammation-associated cellular injury (By similarity). In myeloid
CC cells has a protective role against endotoxemia and bacterial infection
CC by promoting autophagy (By similarity). Involved in endosomal
CC translocation and activation of TLR9 in response to CpG-DNA in
CC macrophages (By similarity). {ECO:0000250|UniProtKB:P63158,
CC ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:21395369}.
CC -!- FUNCTION: In the extracellular compartment (following either active
CC secretion or passive release) involved in regulation of the
CC inflammatory response. Fully reduced HGMB1 (which subsequently gets
CC oxidized after release) in association with CXCL12 mediates the
CC recruitment of inflammatory cells during the initial phase of tissue
CC injury; the CXCL12:HMGB1 complex triggers CXCR4 homodimerization
CC (PubMed:22370717). Induces the migration of monocyte-derived immature
CC dendritic cells and seems to regulate adhesive and migratory functions
CC of neutrophils implicating AGER/RAGE and ITGAM (By similarity). Can
CC bind to various types of DNA and RNA including microbial unmethylated
CC CpG-DNA to enhance the innate immune response to nucleic acids.
CC Proposed to act in promiscuous DNA/RNA sensing which cooperates with
CC subsequent discriminative sensing by specific pattern recognition
CC receptors (By similarity). Promotes extracellular DNA-induced AIM2
CC inflammasome activation implicating AGER/RAGE (PubMed:24971542).
CC Disulfide HMGB1 binds to transmembrane receptors, such as AGER/RAGE,
CC TLR2, TLR4 and probably TREM1, thus activating their signal
CC transduction pathways. Mediates the release of cytokines/chemokines
CC such as TNF, IL-1, IL-6, IL-8, CCL2, CCL3, CCL4 and CXCL10
CC (PubMed:12765338, PubMed:18354232, PubMed:19264983, PubMed:20547845,
CC PubMed:24474694). Promotes secretion of interferon-gamma by macrophage-
CC stimulated natural killer (NK) cells in concert with other cytokines
CC like IL-2 or IL-12 (PubMed:15607795). TLR4 is proposed to be the
CC primary receptor promoting macrophage activation and signaling through
CC TLR4 seems to implicate LY96/MD-2 (PubMed:20547845). In bacterial
CC LPS- or LTA-mediated inflammatory responses binds to the endotoxins and
CC transfers them to CD14 for signaling to the respective TLR4:LY96 and
CC TLR2 complexes (PubMed:18354232, PubMed:21660935, PubMed:25660311).
CC Contributes to tumor proliferation by association with ACER/RAGE (By
CC similarity). Can bind to IL1-beta and signals through the IL1R1:IL1RAP
CC receptor complex (PubMed:18250463). Binding to class A CpG activates
CC cytokine production in plasmacytoid dendritic cells implicating TLR9,
CC MYD88 and AGER/RAGE and can activate autoreactive B cells. Via HMGB1-
CC containing chromatin immune complexes may also promote B cell responses
CC to endogenous TLR9 ligands through a B-cell receptor (BCR)-dependent
CC and ACER/RAGE-independent mechanism (By similarity). Inhibits
CC phagocytosis of apoptotic cells by macrophages; the function is
CC dependent on poly-ADP-ribosylation and involves binding to
CC phosphatidylserine on the cell surface of apoptotic cells (By
CC similarity). In adaptive immunity may be involved in enhancing immunity
CC through activation of effector T cells and suppression of regulatory T
CC (TReg) cells (PubMed:15944249, PubMed:22473704). In contrast, without
CC implicating effector or regulatory T-cells, required for tumor
CC infiltration and activation of T-cells expressing the lymphotoxin
CC LTA:LTB heterotrimer thus promoting tumor malignant progression (By
CC similarity). Also reported to limit proliferation of T-cells (By
CC similarity). Released HMGB1:nucleosome complexes formed during
CC apoptosis can signal through TLR2 to induce cytokine production
CC (PubMed:19064698). Involved in induction of immunological tolerance by
CC apoptotic cells; its pro-inflammatory activities when released by
CC apoptotic cells are neutralized by reactive oxygen species (ROS)-
CC dependent oxidation specifically on Cys-106 (PubMed:18631454). During
CC macrophage activation by activated lymphocyte-derived self apoptotic
CC DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes (By
CC similarity). {ECO:0000250|UniProtKB:P10103,
CC ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159,
CC ECO:0000269|PubMed:12765338, ECO:0000269|PubMed:15607795,
CC ECO:0000269|PubMed:15944249, ECO:0000269|PubMed:18250463,
CC ECO:0000269|PubMed:18354232, ECO:0000269|PubMed:18631454,
CC ECO:0000269|PubMed:19064698, ECO:0000269|PubMed:19264983,
CC ECO:0000269|PubMed:20547845, ECO:0000269|PubMed:21660935,
CC ECO:0000269|PubMed:22370717, ECO:0000269|PubMed:22473704,
CC ECO:0000269|PubMed:24474694, ECO:0000269|PubMed:24971542,
CC ECO:0000269|PubMed:25660311, ECO:0000269|Ref.8}.
CC -!- FUNCTION: (Microbial infection) Critical for entry of human
CC coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus
CC NL63/HCoV-NL63 (PubMed:33147444). Regulates the expression of the pro-
CC viral genes ACE2 and CTSL through chromatin modulation
CC (PubMed:33147444). Required for SARS-CoV-2 ORF3A-induced reticulophagy
CC which induces endoplasmic reticulum stress and inflammatory responses
CC and facilitates viral infection (PubMed:35239449).
CC {ECO:0000269|PubMed:33147444, ECO:0000269|PubMed:35239449}.
CC -!- FUNCTION: (Microbial infection) Associates with the influenza A viral
CC protein NP in the nucleus of infected cells, promoting viral growth and
CC enhancing the activity of the viral polymerase.
CC {ECO:0000269|PubMed:22696656}.
CC -!- FUNCTION: (Microbial infection) Promotes Epstein-Barr virus (EBV)
CC latent-to-lytic switch by sustaining the expression of the viral
CC transcription factor BZLF1 that acts as a molecular switch to induce
CC the transition from the latent to the lytic or productive phase of the
CC virus cycle. Mechanistically, participates in EBV reactivation through
CC the NLRP3 inflammasome. {ECO:0000269|PubMed:34922257}.
CC -!- FUNCTION: (Microbial infection) Facilitates dengue virus propagation
CC via interaction with the untranslated regions of viral genome. In turn,
CC this interaction with viral RNA may regulate secondary structure of
CC dengue RNA thus facilitating its recognition by the replication
CC complex. {ECO:0000269|PubMed:34971702}.
CC -!- SUBUNIT: Interacts (fully reduced HMGB1) with CXCL12; probably in a 1:2
CC ratio involving two molecules of CXCL12, each interacting with one HMG
CC box of HMGB1; inhibited by glycyrrhizin (PubMed:22370717). Associates
CC with the TLR4:LY96 receptor complex (PubMed:20547845). Component of the
CC RAG complex composed of core components RAG1 and RAG2, and associated
CC component HMGB1 or HMGB2 (By similarity). Interacts (in cytoplasm upon
CC starvation) with BECN1; inhibits the interaction of BECN1 and BCL2
CC leading to promotion of autophagy (PubMed:20819940). Interacts with
CC KPNA1; involved in nuclear import (PubMed:17114460). Interacts with
CC SREBF1, TLR2, TLR4, TLR9, PTPRZ1, APEX1, FEN1, POLB, TERT (By
CC similarity). Interacts with IL1B, AGER, MSH2, XPA, XPC, HNF1A, TP53
CC (PubMed:15014079, PubMed:18250463, PubMed:18160415, PubMed:19446504,
CC PubMed:24474694, PubMed:23063560). Interacts with CD24; the probable
CC CD24:SIGLEC10 complex is proposed to inhibit HGMB1-mediated tissue
CC damage immune response (PubMed:19264983). Interacts with THBD; prevents
CC HGMB1 interaction with ACER/RAGE and inhibits HGMB1 pro-inflammatory
CC activity (PubMed:15841214). Interacts with HAVCR2; impairs HMGB1
CC binding to B-DNA and likely HMGB1-mediated innate immune response (By
CC similarity). Interacts with XPO1; mediating nuclear export (By
CC similarity). Interacts with HTT (wild-type and mutant HTT with expanded
CC polyglutamine repeat) (PubMed:23303669). Interacts with receptor
CC RAGE/AGER (PubMed:34743181). {ECO:0000250|UniProtKB:P63158,
CC ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:15014079,
CC ECO:0000269|PubMed:15841214, ECO:0000269|PubMed:17114460,
CC ECO:0000269|PubMed:17803946, ECO:0000269|PubMed:18160415,
CC ECO:0000269|PubMed:18250463, ECO:0000269|PubMed:19264983,
CC ECO:0000269|PubMed:19446504, ECO:0000269|PubMed:20547845,
CC ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:22370717,
CC ECO:0000269|PubMed:23063560, ECO:0000269|PubMed:23303669,
CC ECO:0000269|PubMed:24474694, ECO:0000269|PubMed:34743181}.
CC -!- SUBUNIT: (Microbial infection) Interacts with adenovirus protein pVII;
CC this interaction immobilizes HMGB1 on chromatin, thus preventing its
CC release from cell and subsequent inflammation activation.
CC {ECO:0000269|PubMed:27362237}.
CC -!- SUBUNIT: (Microbial infection) Interacts with SARS-CoV-2 ORF3A protein;
CC the interaction promotes association of HMGB1 with BECN1, promoting
CC reticulophagy which induces endoplasmic reticulum stress and
CC inflammatory responses and facilitates viral infection.
CC {ECO:0000269|PubMed:35239449}.
CC -!- SUBUNIT: (Microbial infection) Interacts with influenza A virus protein
CC NP; this interaction promotes viral replication.
CC {ECO:0000269|PubMed:22696656}.
CC -!- INTERACTION:
CC P09429; Q15109: AGER; NbExp=3; IntAct=EBI-389432, EBI-1646426;
CC P09429; Q6RW13: AGTRAP; NbExp=3; IntAct=EBI-389432, EBI-741181;
CC P09429; P05067: APP; NbExp=3; IntAct=EBI-389432, EBI-77613;
CC P09429; Q14457: BECN1; NbExp=2; IntAct=EBI-389432, EBI-949378;
CC P09429; O95273: CCNDBP1; NbExp=3; IntAct=EBI-389432, EBI-748961;
CC P09429; Q00839: HNRNPU; NbExp=3; IntAct=EBI-389432, EBI-351126;
CC P09429; P42858: HTT; NbExp=13; IntAct=EBI-389432, EBI-466029;
CC P09429; P08729: KRT7; NbExp=6; IntAct=EBI-389432, EBI-297833;
CC P09429; P43246: MSH2; NbExp=2; IntAct=EBI-389432, EBI-355888;
CC P09429; P09874: PARP1; NbExp=2; IntAct=EBI-389432, EBI-355676;
CC P09429; Q96T23: RSF1; NbExp=3; IntAct=EBI-389432, EBI-926768;
CC P09429; P84103: SRSF3; NbExp=3; IntAct=EBI-389432, EBI-372557;
CC P09429; P04637: TP53; NbExp=9; IntAct=EBI-389432, EBI-366083;
CC P09429; Q96B54: ZNF428; NbExp=3; IntAct=EBI-389432, EBI-9995882;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12231511,
CC ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:20819940,
CC ECO:0000269|PubMed:22696656, ECO:0000269|PubMed:22869893,
CC ECO:0000269|PubMed:27362237, ECO:0000269|PubMed:29618516,
CC ECO:0000269|PubMed:33147444}. Chromosome {ECO:0000250|UniProtKB:P10103,
CC ECO:0000250|UniProtKB:P63159, ECO:0000305}. Cytoplasm
CC {ECO:0000269|PubMed:11154118, ECO:0000269|PubMed:12231511,
CC ECO:0000269|PubMed:17114460, ECO:0000269|PubMed:20819940,
CC ECO:0000269|PubMed:22869893, ECO:0000269|PubMed:29618516,
CC ECO:0000269|PubMed:33147444, ECO:0000269|PubMed:34971702}. Secreted
CC {ECO:0000250|UniProtKB:P63158, ECO:0000269|PubMed:12231511,
CC ECO:0000269|PubMed:14532127, ECO:0000269|PubMed:15944249,
CC ECO:0000269|PubMed:19811284, ECO:0000269|PubMed:22869893,
CC ECO:0000269|PubMed:33147444}. Cell membrane
CC {ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159,
CC ECO:0000269|PubMed:11154118}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159,
CC ECO:0000269|PubMed:11154118}; Extracellular side
CC {ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159,
CC ECO:0000269|PubMed:11154118}. Endosome {ECO:0000250|UniProtKB:P63158}.
CC Endoplasmic reticulum-Golgi intermediate compartment
CC {ECO:0000250|UniProtKB:P63158}. Note=In basal state predominantly
CC nuclear. Shuttles between the cytoplasm and the nucleus
CC (PubMed:12231511, PubMed:17114460). Translocates from the nucleus to
CC the cytoplasm upon autophagy stimulation (PubMed:20819940). Release
CC from macrophages in the extracellular milieu requires the activation of
CC NLRC4 or NLRP3 inflammasomes (By similarity). Passively released to the
CC extracellular milieu from necrotic cells by diffusion, involving the
CC fully reduced HGMB1 which subsequently gets oxidized (PubMed:19811284).
CC Also released from apoptotic cells (PubMed:16855214, PubMed:18631454).
CC Active secretion from a variety of immune and non-immune cells such as
CC macrophages, monocytes, neutrophils, dendritic cells and natural killer
CC cells in response to various stimuli such as LPS and cytokines involves
CC a nonconventional secretory process via secretory lysosomes
CC (PubMed:12231511, PubMed:14532127, PubMed:15944249). Secreted by plasma
CC cells in response to LPS (By similarity). Found on the surface of
CC activated platelets (PubMed:11154118). An increased chromatin
CC association is observed when associated with the adenovirus protein
CC pVII (PubMed:27362237). {ECO:0000250|UniProtKB:P63158,
CC ECO:0000269|PubMed:11154118, ECO:0000269|PubMed:12231511,
CC ECO:0000269|PubMed:14532127, ECO:0000269|PubMed:15944249,
CC ECO:0000269|PubMed:16855214, ECO:0000269|PubMed:17114460,
CC ECO:0000269|PubMed:18631454, ECO:0000269|PubMed:19811284,
CC ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:27362237,
CC ECO:0000305|PubMed:20123072}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:35239449}. Note=(Microbial infection) SARS-COV-2
CC ORF3A promotes HMGB1 translocation from the nucleus to the cytoplasm
CC where it is recruited by and colocalizes with ORF3A at the endoplasmic
CC reticulum. {ECO:0000269|PubMed:35239449}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in platelets
CC (PubMed:11154118). {ECO:0000269|PubMed:11154118}.
CC -!- INDUCTION: (Microbial infection) Protein levels increase upon infection
CC by human coronavirus SARS-CoV-2. {ECO:0000269|PubMed:33147444}.
CC -!- DOMAIN: HMG box 2 mediates pro-inflammatory cytokine-stimulating
CC activity and binding to TLR4 (PubMed:12765338, PubMed:20547845).
CC However, not involved in mediating immunogenic activity in the context
CC of apoptosis-induced immune tolerance (PubMed:24474694).
CC {ECO:0000269|PubMed:12765338, ECO:0000269|PubMed:20547845,
CC ECO:0000269|PubMed:24474694}.
CC -!- DOMAIN: The acidic C-terminal domain forms a flexible structure which
CC can reversibly interact intramolecularily with the HMG boxes and
CC modulate binding to DNA and other proteins (PubMed:23063560).
CC {ECO:0000250|UniProtKB:P63159, ECO:0000305|PubMed:23063560}.
CC -!- PTM: Phosphorylated at serine residues. Phosphorylation in both NLS
CC regions is required for cytoplasmic translocation followed by secretion
CC (PubMed:17114460). {ECO:0000269|PubMed:17114460}.
CC -!- PTM: Acetylated on multiple sites upon stimulation with LPS
CC (PubMed:22801494). Acetylation on lysine residues in the nuclear
CC localization signals (NLS 1 and NLS 2) leads to cytoplasmic
CC localization and subsequent secretion (By similarity). Acetylation on
CC Lys-3 results in preferential binding to DNA ends and impairs DNA
CC bending activity (By similarity). {ECO:0000250|UniProtKB:P10103,
CC ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:22801494}.
CC -!- PTM: Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-
CC 106 and a possible intramolecular disulfide bond involving Cys-23 and
CC Cys-45 give rise to different redox forms with specific functional
CC activities in various cellular compartments: 1- fully reduced HMGB1
CC (HMGB1C23hC45hC106h), 2- disulfide HMGB1 (HMGB1C23-C45C106h) and
CC 3- sulfonyl HMGB1 (HMGB1C23soC45soC106so).
CC {ECO:0000269|PubMed:16962095, ECO:0000269|PubMed:19811284,
CC ECO:0000269|PubMed:22869893, ECO:0000305|PubMed:24531895}.
CC -!- PTM: Poly-ADP-ribosylated by PARP1 when secreted following stimulation
CC with LPS (By similarity). {ECO:0000250|UniProtKB:P63158}.
CC -!- PTM: In vitro cleavage by CASP1 is liberating a HMG box 1-containing
CC peptide which may mediate immunogenic activity; the peptide antagonizes
CC apoptosis-induced immune tolerance (PubMed:24474694). Can be
CC proteolytically cleaved by a thrombin:thrombomodulin complex; reduces
CC binding to heparin and pro-inflammatory activities (By similarity).
CC {ECO:0000250|UniProtKB:P10103, ECO:0000269|PubMed:24474694}.
CC -!- PTM: Forms covalent cross-links mediated by transglutaminase TGM2,
CC between a glutamine and the epsilon-amino group of a lysine residue,
CC forming homopolymers and heteropolymers. {ECO:0000269|PubMed:29618516}.
CC -!- MISCELLANEOUS: Proposed to contribute to the pathogenesis of various
CC chronic inflammatory and autoimmune diseases, and cancer. High serum
CC levels are found in several inflammatory events including sepsis,
CC rheumatoid arthritis, artherosclerosis chronic kidney disease, systemic
CC lupus erythematosus (SLE). Seems to be implicated in other diseases
CC characterized by cell death and damage, including diabetes and
CC Alzheimer's disease. Its nucleosome-associated release during secondary
CC necrosis may play a role in SLE (PubMed:19064698). During chemotherapy
CC can mediate regrowth and metastasis of remaining cells in a AGER/RAGE-
CC dependent manner (PubMed:23040637). Purified HMG box 1 acts as a
CC specific antagonist to HGMB1 pro-inflammatory activities
CC (PubMed:14695889). {ECO:0000269|PubMed:14695889,
CC ECO:0000269|PubMed:23040637, ECO:0000305, ECO:0000305|PubMed:19064698,
CC ECO:0000305|PubMed:24220159, ECO:0000305|PubMed:26078984}.
CC -!- SIMILARITY: Belongs to the HMGB family. {ECO:0000305}.
CC -!- CAUTION: Inconsistent experimental results may reflect the use of
CC inconsistently defined redox forms. A recombinant fully reduced form
CC has been used in a number of experiments. However, the redox states of
CC HMGB1 administered in vivo, may interconvert among each other. Purified
CC HMGB1 by itself has only weak pro-inflammatory activity. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/hmgb1/";
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DR EMBL; X12597; CAA31110.1; -; mRNA.
DR EMBL; U51677; AAB08987.1; -; Genomic_DNA.
DR EMBL; D63874; BAA09924.1; -; mRNA.
DR EMBL; EF157968; ABM47301.1; -; Genomic_DNA.
DR EMBL; AY377859; AAQ91389.1; -; mRNA.
DR EMBL; AK291494; BAF84183.1; -; mRNA.
DR EMBL; AK122825; BAG53745.1; -; mRNA.
DR EMBL; CR749614; CAH18408.1; -; mRNA.
DR EMBL; CR456863; CAG33144.1; -; mRNA.
DR EMBL; BT006940; AAP35586.1; -; mRNA.
DR EMBL; BT020159; AAV38961.1; -; mRNA.
DR EMBL; EU012027; ABS29271.1; -; Genomic_DNA.
DR EMBL; AL353648; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08457.1; -; Genomic_DNA.
DR EMBL; BC003378; AAH03378.1; -; mRNA.
DR EMBL; BC030981; AAH30981.1; -; mRNA.
DR EMBL; BC066889; AAH66889.1; -; mRNA.
DR EMBL; BC067732; AAH67732.1; -; mRNA.
DR EMBL; BC141844; AAI41845.1; -; mRNA.
DR CCDS; CCDS9335.1; -.
DR PIR; S02826; S02826.
DR RefSeq; NP_001300821.1; NM_001313892.1.
DR RefSeq; NP_001300822.1; NM_001313893.1.
DR RefSeq; NP_002119.1; NM_002128.5.
DR PDB; 2LY4; NMR; -; A=2-84.
DR PDB; 2RTU; NMR; -; A=1-84.
DR PDB; 2YRQ; NMR; -; A=1-166.
DR PDB; 6CG0; EM; 3.17 A; N=15-140.
DR PDB; 6CIJ; EM; 3.90 A; N=1-163.
DR PDB; 6CIK; X-ray; 3.15 A; N=1-163.
DR PDB; 6CIL; X-ray; 4.15 A; N=1-163.
DR PDB; 6CIM; X-ray; 3.60 A; N=1-163.
DR PDB; 6OEM; EM; 3.60 A; H/N=15-155.
DR PDB; 6OEN; EM; 4.30 A; H/N=1-163.
DR PDB; 6OEO; EM; 3.69 A; N=1-163.
DR PDBsum; 2LY4; -.
DR PDBsum; 2RTU; -.
DR PDBsum; 2YRQ; -.
DR PDBsum; 6CG0; -.
DR PDBsum; 6CIJ; -.
DR PDBsum; 6CIK; -.
DR PDBsum; 6CIL; -.
DR PDBsum; 6CIM; -.
DR PDBsum; 6OEM; -.
DR PDBsum; 6OEN; -.
DR PDBsum; 6OEO; -.
DR AlphaFoldDB; P09429; -.
DR BMRB; P09429; -.
DR PCDDB; P09429; -.
DR SMR; P09429; -.
DR BioGRID; 109389; 417.
DR CORUM; P09429; -.
DR DIP; DIP-24195N; -.
DR IntAct; P09429; 272.
DR MINT; P09429; -.
DR STRING; 9606.ENSP00000345347; -.
DR BindingDB; P09429; -.
DR ChEMBL; CHEMBL2311236; -.
DR DrugBank; DB00608; Chloroquine.
DR DrugBank; DB05869; Ethyl pyruvate.
DR GlyCosmos; P09429; 2 sites, 1 glycan.
DR GlyGen; P09429; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; P09429; -.
DR MetOSite; P09429; -.
DR PhosphoSitePlus; P09429; -.
DR SwissPalm; P09429; -.
DR BioMuta; HMGB1; -.
DR DMDM; 123369; -.
DR DOSAC-COBS-2DPAGE; P09429; -.
DR EPD; P09429; -.
DR jPOST; P09429; -.
DR MassIVE; P09429; -.
DR MaxQB; P09429; -.
DR PaxDb; P09429; -.
DR PeptideAtlas; P09429; -.
DR ProteomicsDB; 52217; -.
DR TopDownProteomics; P09429; -.
DR ABCD; P09429; 23 sequenced antibodies.
DR Antibodypedia; 3132; 1791 antibodies from 46 providers.
DR DNASU; 3146; -.
DR Ensembl; ENST00000339872.8; ENSP00000343040.4; ENSG00000189403.15.
DR Ensembl; ENST00000341423.10; ENSP00000345347.5; ENSG00000189403.15.
DR Ensembl; ENST00000399494.5; ENSP00000382417.1; ENSG00000189403.15.
DR Ensembl; ENST00000405805.5; ENSP00000384678.1; ENSG00000189403.15.
DR GeneID; 3146; -.
DR KEGG; hsa:3146; -.
DR MANE-Select; ENST00000341423.10; ENSP00000345347.5; NM_002128.7; NP_002119.1.
DR UCSC; uc001usx.5; human.
DR AGR; HGNC:4983; -.
DR CTD; 3146; -.
DR DisGeNET; 3146; -.
DR GeneCards; HMGB1; -.
DR HGNC; HGNC:4983; HMGB1.
DR HPA; ENSG00000189403; Low tissue specificity.
DR MIM; 163905; gene.
DR neXtProt; NX_P09429; -.
DR OpenTargets; ENSG00000189403; -.
DR PharmGKB; PA188; -.
DR VEuPathDB; HostDB:ENSG00000189403; -.
DR eggNOG; KOG0381; Eukaryota.
DR GeneTree; ENSGT00950000183120; -.
DR InParanoid; P09429; -.
DR OMA; PHSANEV; -.
DR OrthoDB; 1222485at2759; -.
DR PhylomeDB; P09429; -.
DR TreeFam; TF105371; -.
DR PathwayCommons; P09429; -.
DR Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR Reactome; R-HSA-140342; Apoptosis induced DNA fragmentation.
DR Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR Reactome; R-HSA-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-HSA-5602498; MyD88 deficiency (TLR2/4).
DR Reactome; R-HSA-5603041; IRAK4 deficiency (TLR2/4).
DR Reactome; R-HSA-5620971; Pyroptosis.
DR Reactome; R-HSA-5686938; Regulation of TLR by endogenous ligand.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-879415; Advanced glycosylation endproduct receptor signaling.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR SignaLink; P09429; -.
DR SIGNOR; P09429; -.
DR BioGRID-ORCS; 3146; 313 hits in 1115 CRISPR screens.
DR ChiTaRS; HMGB1; human.
DR EvolutionaryTrace; P09429; -.
DR GeneWiki; HMGB1; -.
DR GenomeRNAi; 3146; -.
DR Pharos; P09429; Tchem.
DR PRO; PR:P09429; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P09429; protein.
DR Bgee; ENSG00000189403; Expressed in ventricular zone and 179 other tissues.
DR ExpressionAtlas; P09429; baseline and differential.
DR Genevisible; P09429; HS.
DR GO; GO:0035868; C:alphav-beta3 integrin-HMGB1 complex; IDA:BHF-UCL.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0000793; C:condensed chromosome; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0017053; C:transcription repressor complex; IDA:UniProtKB.
DR GO; GO:0000405; F:bubble DNA binding; ISS:AgBase.
DR GO; GO:0019958; F:C-X-C chemokine binding; IDA:UniProtKB.
DR GO; GO:0042056; F:chemoattractant activity; ISS:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; ISS:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB.
DR GO; GO:0008301; F:DNA binding, bending; IMP:UniProtKB.
DR GO; GO:0070182; F:DNA polymerase binding; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0000400; F:four-way junction DNA binding; ISS:AgBase.
DR GO; GO:0005178; F:integrin binding; IDA:BHF-UCL.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:UniProtKB.
DR GO; GO:0016829; F:lyase activity; IDA:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
DR GO; GO:0050786; F:RAGE receptor binding; ISS:UniProtKB.
DR GO; GO:0048018; F:receptor ligand activity; IDA:UniProt.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0097100; F:supercoiled DNA binding; ISS:AgBase.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB.
DR GO; GO:0043277; P:apoptotic cell clearance; IDA:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:ARUK-UCL.
DR GO; GO:0002407; P:dendritic cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0032392; P:DNA geometric change; ISS:AgBase.
DR GO; GO:0006310; P:DNA recombination; ISS:UniProtKB.
DR GO; GO:0006265; P:DNA topological change; ISS:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0031507; P:heterochromatin formation; IGI:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IDA:CACAO.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IEP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0001773; P:myeloid dendritic cell activation; ISS:UniProtKB.
DR GO; GO:2000426; P:negative regulation of apoptotic cell clearance; IDA:BHF-UCL.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:CACAO.
DR GO; GO:0043371; P:negative regulation of CD4-positive, alpha-beta T cell differentiation; IDA:UniProtKB.
DR GO; GO:0017055; P:negative regulation of RNA polymerase II transcription preinitiation complex assembly; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0032689; P:negative regulation of type II interferon production; IDA:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0097350; P:neutrophil clearance; IDA:UniProtKB.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:BHF-UCL.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IDA:CACAO.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR GO; GO:2001200; P:positive regulation of dendritic cell differentiation; IMP:UniProtKB.
DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB.
DR GO; GO:0051106; P:positive regulation of DNA ligation; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0032732; P:positive regulation of interleukin-1 production; IDA:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:UniProtKB.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IMP:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:CACAO.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0032425; P:positive regulation of mismatch repair; IDA:UniProtKB.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IDA:UniProtKB.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:0046598; P:positive regulation of viral entry into host cell; IMP:UniProtKB.
DR GO; GO:0032072; P:regulation of restriction endodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0002840; P:regulation of T cell mediated immune response to tumor cell; ISS:UniProtKB.
DR GO; GO:0002643; P:regulation of tolerance induction; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0035711; P:T-helper 1 cell activation; IDA:UniProtKB.
DR GO; GO:0045063; P:T-helper 1 cell differentiation; IMP:UniProtKB.
DR GO; GO:0033151; P:V(D)J recombination; IDA:UniProtKB.
DR CDD; cd21978; HMG-box_HMGB_rpt1; 1.
DR CDD; cd21979; HMG-box_HMGB_rpt2; 1.
DR DisProt; DP01493; -.
DR Gene3D; 1.10.30.10; High mobility group box domain; 2.
DR IDEAL; IID00297; -.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR017967; HMG_boxA_CS.
DR PANTHER; PTHR48112:SF12; HIGH MOBILITY GROUP PROTEIN B1; 1.
DR PANTHER; PTHR48112; HIGH MOBILITY GROUP PROTEIN DSP1; 1.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF09011; HMG_box_2; 1.
DR PRINTS; PR00886; HIGHMOBLTY12.
DR SMART; SM00398; HMG; 2.
DR SUPFAM; SSF47095; HMG-box; 2.
DR PROSITE; PS00353; HMG_BOX_1; 1.
DR PROSITE; PS50118; HMG_BOX_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Adaptive immunity; ADP-ribosylation; Autophagy;
KW Cell membrane; Chemotaxis; Chromosome; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; DNA damage; DNA recombination;
KW DNA repair; DNA-binding; Endoplasmic reticulum; Endosome;
KW Host-virus interaction; Immunity; Inflammatory response; Innate immunity;
KW Isopeptide bond; Membrane; Nucleus; Oxidation; Phosphoprotein;
KW Reference proteome; Repeat; Secreted.
FT CHAIN 1..215
FT /note="High mobility group protein B1"
FT /id="PRO_0000048526"
FT DNA_BIND 9..79
FT /note="HMG box 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT DNA_BIND 95..163
FT /note="HMG box 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..97
FT /note="Sufficient for interaction with HAVCR2"
FT /evidence="ECO:0000250|UniProtKB:P63158"
FT REGION 3..15
FT /note="LPS binding (delipidated)"
FT /evidence="ECO:0000269|PubMed:21660935"
FT REGION 76..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..96
FT /note="LPS binding (Lipid A)"
FT /evidence="ECO:0000269|PubMed:21660935"
FT REGION 89..108
FT /note="Cytokine-stimulating activity"
FT /evidence="ECO:0000269|PubMed:12765338"
FT REGION 150..183
FT /note="Binding to AGER/RAGE"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT REGION 161..215
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 27..43
FT /note="Nuclear localization signal (NLS) 1"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT MOTIF 178..184
FT /note="Nuclear localization signal (NLS) 2"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT COMPBIAS 76..94
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..187
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..215
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1..10
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT SITE 10..11
FT /note="Cleavage; by thrombin:thrombomodulin"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT SITE 67..68
FT /note="Cleavage; by CASP1"
FT /evidence="ECO:0000269|PubMed:24474694"
FT MOD_RES 3
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 7
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 8
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 12
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 23
FT /note="Cysteine sulfonic acid (-SO3H); alternate"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT MOD_RES 28
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 29
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 30
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 43
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63158"
FT MOD_RES 45
FT /note="Cysteine sulfonic acid (-SO3H); alternate"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT MOD_RES 90
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63158"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 106
FT /note="Cysteine sulfonic acid (-SO3H)"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT MOD_RES 127
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 141
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63158"
FT MOD_RES 172
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 173
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 177
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 180
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 181
FT /note="ADP-ribosylserine"
FT /evidence="ECO:0000269|PubMed:28190768"
FT MOD_RES 182
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 183
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 184
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT MOD_RES 185
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P10103"
FT DISULFID 23..45
FT /note="In disulfide HMGB1; alternate"
FT /evidence="ECO:0000250|UniProtKB:P63159"
FT CROSSLNK 28
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000269|PubMed:29618516"
FT CROSSLNK 43
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000269|PubMed:29618516"
FT CROSSLNK 44
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000269|PubMed:29618516"
FT CROSSLNK 68
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000269|PubMed:29618516"
FT CROSSLNK 180
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000269|PubMed:29618516"
FT CROSSLNK 182
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000269|PubMed:29618516"
FT CROSSLNK 183
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000269|PubMed:29618516"
FT CROSSLNK 184
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000269|PubMed:29618516"
FT VARIANT 11
FT /note="G -> R (in gastric-carcinoma cell line)"
FT /evidence="ECO:0000269|PubMed:9036861"
FT /id="VAR_046451"
FT VARIANT 149
FT /note="A -> E (in gastric-carcinoma cell line)"
FT /evidence="ECO:0000269|PubMed:9036861"
FT /id="VAR_046452"
FT VARIANT 156
FT /note="E -> Q"
FT /evidence="ECO:0000269|Ref.10"
FT /id="VAR_046453"
FT VARIANT 190
FT /note="D -> G (in gastric-carcinoma cell line)"
FT /evidence="ECO:0000269|PubMed:9036861"
FT /id="VAR_046454"
FT MUTAGEN 35
FT /note="S->A: Greatly reduces phosphorylation, nuclear
FT localization; when associated with A-39; A-42; A-46; A-53
FT and A-181."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 35
FT /note="S->E: Cytoplasmic localization (phosphorylation
FT mimicking); when associated with E-39; E-42; E-46; E-53 and
FT E-181."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 39
FT /note="S->A: Greatly reduces phosphorylation, nuclear
FT localization; when associated with A-35; A-42; A-46; A-53
FT and A-181."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 39
FT /note="S->E: Cytoplasmic localization (phosphorylation
FT mimicking); when associated with E-35; E-42; E-46; E-53 and
FT E-181."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 42
FT /note="S->A: Greatly reduces phosphorylation, nuclear
FT localization; when associated with A-35; A-39; A-46; A-53
FT and A-181."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 42
FT /note="S->E: Cytoplasmic localization (phosphorylation
FT mimicking); when associated with E-35; E-39; E-46; E-53 and
FT E-181."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 46
FT /note="S->A: Greatly reduces phosphorylation, nuclear
FT localization; when associated with A-35; A-39; A-42; A-53
FT and A-181."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 46
FT /note="S->E: Cytoplasmic localization (phosphorylation
FT mimicking); when associated with E-35; E-39; E-42; E-53 and
FT E-181."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 53
FT /note="S->A: Greatly reduces phosphorylation, nuclear
FT localization; when associated with A-35; A-39; A-42; A-46
FT and A-181."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 53
FT /note="S->E: Cytoplasmic localization (phosphorylation
FT mimicking); when associated with E-35; E-39; E-42; E-46 and
FT E-181."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 67
FT /note="D->A: Abolishes cleavage by CASP1 and impairs
FT ability to antagonize apoptosis-induced immune tolerance."
FT /evidence="ECO:0000269|PubMed:24474694"
FT MUTAGEN 106
FT /note="C->S: Inhibits oxidation-dependent inactivation of
FT immunostimmulatory activity in apoptotic cells."
FT /evidence="ECO:0000269|PubMed:18631454"
FT MUTAGEN 181
FT /note="S->A: Greatly reduces phosphorylation, nuclear
FT localization; when associated with A-35; A-39; A-42; A-46
FT and A-53."
FT /evidence="ECO:0000269|PubMed:17114460"
FT MUTAGEN 181
FT /note="S->E: Cytoplasmic localization (phosphorylation
FT mimicking); when associated with E-35; E-39; E-42; E-46 and
FT E-53."
FT /evidence="ECO:0000269|PubMed:17114460"
FT CONFLICT 143
FT /note="P -> H (in Ref. 13; AAI41845)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="E -> D (in Ref. 8; CAG33144)"
FT /evidence="ECO:0000305"
FT STRAND 1..3
FT /evidence="ECO:0007829|PDB:2YRQ"
FT STRAND 6..8
FT /evidence="ECO:0007829|PDB:2YRQ"
FT HELIX 20..30
FT /evidence="ECO:0007829|PDB:6CIK"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:6CIK"
FT HELIX 38..47
FT /evidence="ECO:0007829|PDB:6CIK"
FT HELIX 54..76
FT /evidence="ECO:0007829|PDB:2LY4"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:2YRQ"
FT HELIX 101..116
FT /evidence="ECO:0007829|PDB:6CIK"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:2YRQ"
FT HELIX 122..135
FT /evidence="ECO:0007829|PDB:6CIK"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:2YRQ"
FT HELIX 142..157
FT /evidence="ECO:0007829|PDB:6CIK"
SQ SEQUENCE 215 AA; 24894 MW; 8A868CF277D417B5 CRC64;
MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKKCSERWK TMSAKEKGKF
EDMAKADKAR YEREMKTYIP PKGETKKKFK DPNAPKRPPS AFFLFCSEYR PKIKGEHPGL
SIGDVAKKLG EMWNNTAADD KQPYEKKAAK LKEKYEKDIA AYRAKGKPDA AKKGVVKAEK
SKKKKEEEED EEDEEDEEEE EDEEDEDEEE DDDDE
//