HMGB1_RAT
ID HMGB1_RAT Reviewed; 215 AA.
AC P63159; P07155; P27109; P27428; Q548R9;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=High mobility group protein B1;
DE AltName: Full=Amphoterin;
DE AltName: Full=Heparin-binding protein p30;
DE AltName: Full=High mobility group protein 1;
DE Short=HMG-1;
GN Name=Hmgb1; Synonyms=Hmg-1, Hmg1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=3684582; DOI=10.1093/nar/15.21.9077;
RA Paonessa G., Frank R., Cortese R.;
RT "Nucleotide sequence of rat liver HMG1 cDNA.";
RL Nucleic Acids Res. 15:9077-9077(1987).
RN [2]
RP SEQUENCE REVISION.
RA Bianchi M.;
RL Submitted (DEC-1988) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION,
RP AND FUNCTION.
RX PubMed=1885601; DOI=10.1016/s0021-9258(18)55361-8;
RA Merenmies J., Pihlaskari R., Laitinen J., Wartiovaara J., Rauvala H.;
RT "30-kDa heparin-binding protein of brain (amphoterin) involved in neurite
RT outgrowth. Amino acid sequence and localization in the filopodia of the
RT advancing plasma membrane.";
RL J. Biol. Chem. 266:16722-16729(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RA Ito T., Suzuki A., Horimoto N., Imai E., Hori M.;
RT "Amphoterin is associated with the development of the kidney.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, Prostate, 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 [6]
RP PROTEIN SEQUENCE OF 2-21, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=2461949; DOI=10.1083/jcb.107.6.2293;
RA Rauvala H., Merenmies J., Pihlaskari R., Korkolainen M., Huhtala M.L.,
RA Panula P.;
RT "The adhesive and neurite-promoting molecule p30: analysis of the amino-
RT terminal sequence and production of antipeptide antibodies that detect p30
RT at the surface of neuroblastoma cells and of brain neurons.";
RL J. Cell Biol. 107:2293-2305(1988).
RN [7]
RP DNA-BINDING.
RX PubMed=2922595; DOI=10.1126/science.2922595;
RA Bianchi M.E., Beltrame M., Paonessa G.;
RT "Specific recognition of cruciform DNA by nuclear protein HMG1.";
RL Science 243:1056-1059(1989).
RN [8]
RP FUNCTION.
RX PubMed=7592757; DOI=10.1074/jbc.270.43.25752;
RA Hori O., Brett J., Slattery T., Cao R., Zhang J., Chen J.X., Nagashima M.,
RA Lundh E.R., Vijay S., Nitecki D.;
RT "The receptor for advanced glycation end products (RAGE) is a cellular
RT binding site for amphoterin. Mediation of neurite outgrowth and co-
RT expression of rage and amphoterin in the developing nervous system.";
RL J. Biol. Chem. 270:25752-25761(1995).
RN [9]
RP INTERACTION WITH PTPRZ1.
RX PubMed=9507007; DOI=10.1074/jbc.273.12.6998;
RA Milev P., Chiba A., Haring M., Rauvala H., Schachner M., Ranscht B.,
RA Margolis R.K., Margolis R.U.;
RT "High affinity binding and overlapping localization of neurocan and
RT phosphacan/protein-tyrosine phosphatase-zeta/beta with tenascin-R,
RT amphoterin, and the heparin-binding growth-associated molecule.";
RL J. Biol. Chem. 273:6998-7005(1998).
RN [10]
RP FUNCTION.
RX PubMed=10866811; DOI=10.1046/j.1432-1327.2000.01450.x;
RA Stros M., Cherny D., Jovin T.M.;
RT "HMG1 protein stimulates DNA end joining by promoting association of DNA
RT molecules via their ends.";
RL Eur. J. Biochem. 267:4088-4097(2000).
RN [11]
RP FUNCTION.
RX PubMed=10952726; DOI=10.1084/jem.192.4.565;
RA Andersson U., Wang H., Palmblad K., Aveberger A.C., Bloom O.,
RA Erlandsson-Harris H., Janson A., Kokkola R., Zhang M., Yang H.,
RA Tracey K.J.;
RT "High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine
RT synthesis in human monocytes.";
RL J. Exp. Med. 192:565-570(2000).
RN [12]
RP FUNCTION.
RX PubMed=10830965; DOI=10.1038/35012626;
RA Taguchi A., Blood D.C., del Toro G., Canet A., Lee D.C., Qu W., Tanji N.,
RA Lu Y., Lalla E., Fu C., Hofmann M.A., Kislinger T., Ingram M., Lu A.,
RA Tanaka H., Hori O., Ogawa S., Stern D.M., Schmidt A.M.;
RT "Blockade of RAGE-amphoterin signalling suppresses tumour growth and
RT metastases.";
RL Nature 405:354-360(2000).
RN [13]
RP PHOSPHOLIPID-BINDING.
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 [14]
RP DNA-BINDING, AND DOMAIN.
RX PubMed=11513603; DOI=10.1021/bi0100900;
RA Mueller S., Bianchi M.E., Knapp S.;
RT "Thermodynamics of HMGB1 interaction with duplex DNA.";
RL Biochemistry 40:10254-10261(2001).
RN [15]
RP FUNCTION, AND LIGAND FOR AGER RECEPTOR.
RX PubMed=12183440;
RA Huttunen H.J., Fages C., Kuja-Panula J., Ridley A.J., Rauvala H.;
RT "Receptor for advanced glycation end products-binding COOH-terminal motif
RT of amphoterin inhibits invasive migration and metastasis.";
RL Cancer Res. 62:4805-4811(2002).
RN [16]
RP FUNCTION.
RX PubMed=12486007; DOI=10.1093/emboj/cdf692;
RA Bonaldi T., Langst G., Strohner R., Becker P.B., Bianchi M.E.;
RT "The DNA chaperone HMGB1 facilitates ACF/CHRAC-dependent nucleosome
RT sliding.";
RL EMBO J. 21:6865-6873(2002).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=12110890; DOI=10.1038/nature00858;
RA Scaffidi P., Misteli T., Bianchi M.E.;
RT "Release of chromatin protein HMGB1 by necrotic cells triggers
RT inflammation.";
RL Nature 418:191-195(2002).
RN [18]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF 28-LYS--LYS-30 AND 182-LYS--LYS-184,
RP AND INTERACTION WITH XPO1.
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 [19]
RP DOMAIN.
RX PubMed=15379539; DOI=10.1021/bi049364k;
RA Knapp S., Mueller S., Digilio G., Bonaldi T., Bianchi M.E., Musco G.;
RT "The long acidic tail of high mobility group box 1 (HMGB1) protein forms an
RT extended and flexible structure that interacts with specific residues
RT within and between the HMG boxes.";
RL Biochemistry 43:11992-11997(2004).
RN [20]
RP SUBCELLULAR LOCATION, CHROMATIN-BINDING, AND MUTAGENESIS OF PHE-38; PHE-103
RP AND ILE-122.
RX PubMed=15808513; DOI=10.1016/j.molcel.2005.03.005;
RA Agresti A., Scaffidi P., Riva A., Caiolfa V.R., Bianchi M.E.;
RT "GR and HMGB1 interact only within chromatin and influence each other's
RT residence time.";
RL Mol. Cell 18:109-121(2005).
RN [21]
RP DISULFIDE BRIDGE, REDOX FORMS, AND MUTAGENESIS OF CYS-23; CYS-45 AND
RP CYS-106.
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 [22]
RP ACETYLATION AT LYS-3.
RX PubMed=17269659; DOI=10.1021/bi0614479;
RA Ugrinova I., Mitkova E., Moskalenko C., Pashev I., Pasheva E.;
RT "DNA bending versus DNA end joining activity of HMGB1 protein is modulated
RT in vitro by acetylation.";
RL Biochemistry 46:2111-2117(2007).
RN [23]
RP FUNCTION.
RX PubMed=18277947; DOI=10.1097/shk.0b013e3181672495;
RA Zhang L.T., Yao Y.M., Dong Y.Q., Dong N., Yu Y., Sheng Z.Y.;
RT "Relationship between high-mobility group box 1 protein release and T-cell
RT suppression in rats after thermal injury.";
RL Shock 30:449-455(2008).
RN [24]
RP INTERACTION WITH BECN1, AND MUTAGENESIS OF CYS-23; CYS-45 AND CYS-106.
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 [25]
RP FUNCTION, LIGAND FOR TLR4:LY96 RECEPTOR COMPLEX, AND MUTAGENESIS OF
RP CYS-106.
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 [26]
RP REDOX FORMS, FUNCTION, INTERACTION WITH CXCL12, SUBCELLULAR LOCATION, AND
RP OXIDATION AT CYS-106.
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 [27]
RP REDOX FORMS, AND MUTAGENESIS OF CYS-45.
RX PubMed=22105604; DOI=10.2119/molmed.2011.00389;
RA Yang H., Lundback P., Ottosson L., Erlandsson-Harris H., Venereau E.,
RA Bianchi M.E., Al-Abed Y., Andersson U., Tracey K.J., Antoine D.J.;
RT "Redox modification of cysteine residues regulates the cytokine activity of
RT high mobility group box-1 (HMGB1).";
RL Mol. Med. 18:250-259(2012).
RN [28]
RP REVIEW ON FUNCTION RELATED TO ADAPTIVE IMUNNITY.
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 [29]
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 [30]
RP FUNCTION.
RX PubMed=23508573; DOI=10.2119/molmed.2012.00306;
RA Kim S., Kim S.Y., Pribis J.P., Lotze M., Mollen K.P., Shapiro R.,
RA Loughran P., Scott M.J., Billiar T.R.;
RT "Signaling of high mobility group box 1 (HMGB1) through toll-like receptor
RT 4 in macrophages requires CD14.";
RL Mol. Med. 19:88-98(2013).
RN [31]
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 [32]
RP FUNCTION, AND REDOX FORMS.
RX PubMed=24551219; DOI=10.1371/journal.pone.0089070;
RA Polanska E., Pospisilova S., Stros M.;
RT "Binding of histone H1 to DNA is differentially modulated by redox state of
RT HMGB1.";
RL PLoS ONE 9:E89070-E89070(2014).
RN [33]
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 [34]
RP STRUCTURE BY NMR OF 88-165.
RX PubMed=8467791; DOI=10.1002/j.1460-2075.1993.tb05776.x;
RA Weir H.M., Kraulis P.J., Hill C.S., Raine A.R.C., Laue E.D., Thomas J.O.;
RT "Structure of the HMG box motif in the B-domain of HMG1.";
RL EMBO J. 12:1311-1319(1993).
RN [35]
RP STRUCTURE BY NMR OF 1-84.
RC STRAIN=Sprague-Dawley;
RX PubMed=8527432; DOI=10.1021/bi00051a007;
RA Hardman C.H., Broadhurst R.W., Raine A.R.C., Grasser K.D., Thomas J.O.,
RA Laue E.D.;
RT "Structure of the A-domain of HMG1 and its interaction with DNA as studied
RT by heteronuclear three- and four-dimensional NMR spectroscopy.";
RL Biochemistry 34:16596-16607(1995).
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. Proposed to be an
CC universal biosensor for nucleic acids. Promotes host inflammatory
CC response to sterile and infectious signals and is involved in the
CC coordination and integration of innate and adaptive immune responses.
CC In the cytoplasm functions as sensor and/or chaperone for immunogenic
CC nucleic acids implicating the activation of TLR9-mediated immune
CC responses, and mediates autophagy. Acts as danger associated molecular
CC pattern (DAMP) molecule that amplifies immune responses during tissue
CC injury. Released to the extracellular environment can bind DNA,
CC nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE,
CC lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates
CC cells through engagement of multiple surface receptors. In the
CC extracellular compartment fully reduced HMGB1 (released by necrosis)
CC acts as a chemokine, disulfide HMGB1 (actively secreted) as a cytokine,
CC and sulfonyl HMGB1 (released from apoptotic cells) promotes
CC immunological tolerance (PubMed:23519706, PubMed:23446148,
CC PubMed:23994764, PubMed:25048472). Has proangiogenic activity. May be
CC involved in platelet activation. Binds to phosphatidylserine and
CC phosphatidylethanolamide (PubMed:11154118). Bound to RAGE mediates
CC signaling for neuronal outgrowth (PubMed:1885601, PubMed:2461949,
CC PubMed:7592757, PubMed:12183440). May play a role in accumulation of
CC expanded polyglutamine (polyQ) proteins. {ECO:0000250|UniProtKB:P09429,
CC ECO:0000250|UniProtKB:P10103, ECO:0000250|UniProtKB:P63158,
CC ECO:0000269|PubMed:11154118, ECO:0000269|PubMed:12183440,
CC ECO:0000269|PubMed:1885601, ECO:0000269|PubMed:2461949,
CC ECO:0000269|PubMed:7592757, ECO:0000305|PubMed:23446148,
CC ECO:0000305|PubMed:23519706, ECO:0000305|PubMed:23994764,
CC 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
CC (PubMed:2922595, PubMed:11513603). Can bent DNA and enhance DNA
CC flexibility by looping thus providing a mechanism to promote activities
CC on various gene promoters by enhancing transcription factor binding
CC and/or bringing distant regulatory sequences into close proximity
CC (PubMed:12486007). May be involved in nucleotide excision repair (NER),
CC mismatch repair (MMR) and base excision repair (BER) pathways, and
CC double strand break repair such as non-homologous end joining (NHEJ)
CC (PubMed:10866811). Involved in V(D)J recombination by acting as a
CC cofactor of the RAG complex: acts by stimulating cleavage and RAG
CC protein binding at the 23 bp spacer of conserved recombination signal
CC sequences (RSS) (By similarity). In vitro can displace histone H1 from
CC highly bent DNA (PubMed:24551219). Can restructure the canonical
CC nucleosome leading to relaxation of structural constraints for
CC transcription factor-binding (By similarity). Enhances binding of
CC sterol regulatory element-binding proteins (SREBPs) such as SREBF1 to
CC their cognate DNA sequences and increases their transcriptional
CC activities (By similarity). Facilitates binding of TP53 to DNA (By
CC similarity). May be involved in mitochondrial quality control and
CC autophagy in a transcription-dependent fashion implicating HSPB1 (By
CC similarity). Can modulate the activity of the telomerase complex and
CC may be involved in telomere maintenance (By similarity).
CC {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P10103,
CC ECO:0000250|UniProtKB:P63158, ECO:0000269|PubMed:10866811,
CC ECO:0000269|PubMed:11513603, ECO:0000269|PubMed:12486007,
CC ECO:0000269|PubMed:24551219, ECO:0000269|PubMed:2922595}.
CC -!- FUNCTION: In the cytoplasm proposed to dissociate the BECN1:BCL2
CC complex via competitive interaction with BECN1 leading to autophagy
CC activation (By similarity). 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:P09429,
CC ECO:0000250|UniProtKB:P63158}.
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:22869893). 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. Promotes extracellular DNA-induced AIM2 inflammasome
CC activation implicating AGER/RAGE (By similarity). Disulfide HMGB1 binds
CC to transmembrane receptors, such as AGER/RAGE, TLR2, TLR4 and probably
CC TREM1, thus activating their signal transduction pathways. Mediates the
CC release of cytokines/chemokines such as TNF, IL-1, IL-6, IL-8, CCL2,
CC CCL3, CCL4 and CXCL10 (PubMed:10952726, PubMed:20547845,
CC PubMed:22869893). 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. TLR4 is proposed to be the primary receptor
CC promoting macrophage activation and signaling through TLR4 seems to
CC implicate LY96/MD-2 (By similarity). In bacterial LPS- or LTA-mediated
CC inflammatory responses binds to the endotoxins and transfers them to
CC CD14 for signaling to the respective TLR4:LY96 and TLR2 complexes
CC (PubMed:23508573). Contributes to tumor proliferation by association
CC with ACER/RAGE (PubMed:10830965). Can bind to IL1-beta and signals
CC through the IL1R1:IL1RAP receptor complex (By similarity). Binding to
CC class A CpG activates cytokine production in plasmacytoid dendritic
CC cells implicating TLR9, MYD88 and AGER/RAGE and can activate
CC autoreactive B cells (By similarity). Via HMGB1-containing chromatin
CC immune complexes may also promote B cell responses to endogenous TLR9
CC ligands through a B-cell receptor (BCR)-dependent and ACER/RAGE-
CC independent mechanism (By similarity). Inhibits phagocytosis of
CC apoptotic cells by macrophages; the function is dependent on poly-ADP-
CC ribosylation and involves binding to phosphatidylserine on the cell
CC surface of apoptotic cells (By similarity). In adaptive immunity may be
CC involved in enhancing immunity through activation of effector T-cells
CC and suppression of regulatory T (TReg) cells (By similarity). In
CC contrast, without implicating effector or regulatory T-cells, required
CC for tumor infiltration and activation of T-cells expressing the
CC lymphotoxin LTA:LTB heterotrimer thus promoting tumor malignant
CC progression (By similarity). Also reported to limit proliferation of T-
CC cells (PubMed:18277947). Released HMGB1:nucleosome complexes formed
CC during apoptosis can signal through TLR2 to induce cytokine production.
CC Involved in induction of immunological tolerance by apoptotic cells;
CC its pro-inflammatory activities when released by apoptotic cells are
CC neutralized by reactive oxygen species (ROS)-dependent oxidation
CC specifically on Cys-106 (By similarity). During macrophage activation
CC by activated lymphocyte-derived self apoptotic DNA (ALD-DNA) promotes
CC recruitment of ALD-DNA to endosomes (By similarity).
CC {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P10103,
CC ECO:0000250|UniProtKB:P63158, ECO:0000269|PubMed:10830965,
CC ECO:0000269|PubMed:10952726, ECO:0000269|PubMed:18277947,
CC ECO:0000269|PubMed:22869893}.
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:22869893). 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 (By similarity). Interacts with AGER
CC (PubMed:12183440). Interacts with PTPRZ1 isoform 3/phosphacan
CC (PubMed:9507007). Interacts with SREBF1, TLR2, TLR4, TLR9, APEX1, FEN1,
CC POLB, TERT, IL1B, MSH2, XPA, XPC, HNF1A, TP53 (By similarity).
CC Interacts with CD24; the probable CD24:SIGLEC10 complex is proposed to
CC inhibit HGMB1-mediated tissue damage immune response. Interacts with
CC THBD; prevents HGMB1 interaction with ACER/RAGE and inhibits HGMB1 pro-
CC inflammatory activity. Interacts with HAVCR2; impairs HMGB1 binding to
CC B-DNA and likely HMGB1-mediated innate immune response (By similarity).
CC Interacts with XPO1; mediating nuclear export (PubMed:14532127).
CC {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P63158,
CC ECO:0000269|PubMed:12183440, ECO:0000269|PubMed:14532127,
CC ECO:0000269|PubMed:20547845, ECO:0000269|PubMed:20819940,
CC ECO:0000269|PubMed:22869893}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22869893}. Cytoplasm
CC {ECO:0000269|PubMed:22869893}. Secreted {ECO:0000250|UniProtKB:P63158,
CC ECO:0000269|PubMed:1885601, ECO:0000269|PubMed:22869893}. Chromosome
CC {ECO:0000269|PubMed:12110890, ECO:0000269|PubMed:15808513}. Cell
CC membrane {ECO:0000269|PubMed:1885601, ECO:0000269|PubMed:2461949};
CC Peripheral membrane protein {ECO:0000269|PubMed:1885601,
CC ECO:0000269|PubMed:2461949}; Extracellular side
CC {ECO:0000269|PubMed:2461949}. 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. Nuclear export
CC is in part XPO1-dependent implicating NES contained in both HMG boxes 1
CC and 2 (PubMed:14532127). Release from macrophages in the extracellular
CC milieu requires the activation of NLRC4 or NLRP3 inflammasomes (By
CC similarity). Passively released to the extracellular milieu from
CC necrotic cells by diffusion, involving the fully reduced form which
CC subsequently gets oxidized (PubMed:22869893). Actively secreted from a
CC variety of immune and non-immune cells such as macrophages, monocytes,
CC neutrophils, dendritic cells and natural killer cells in response to
CC various stimuli, involving a nonconventional secretory process via
CC secretory lysosomes. Secreted by plasma cells in response to LPS (By
CC similarity). Associated with the plasma membrane of filipodia in
CC process-growing cells, and also deposited into the substrate-attached
CC material (PubMed:1885601). {ECO:0000250|UniProtKB:P63158,
CC ECO:0000269|PubMed:14532127, ECO:0000269|PubMed:15808513,
CC ECO:0000269|PubMed:1885601, ECO:0000269|PubMed:22869893}.
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.
CC {ECO:0000269|PubMed:11513603, ECO:0000269|PubMed:15379539}.
CC -!- PTM: Phosphorylated at serine residues. Phosphorylation in both NLS
CC regions is required for cytoplasmic translocation followed by
CC secretion. {ECO:0000250|UniProtKB:P09429}.
CC -!- PTM: Acetylated on multiple sites upon stimulation with LPS (By
CC similarity). Acetylation on lysine residues in the nuclear localization
CC signals (NLS 1 and NLS 2) leads to cytoplasmic localization and
CC subsequent secretion (PubMed:14532127). Acetylation on Lys-3 results in
CC preferential binding to DNA ends and impairs DNA bending activity
CC (PubMed:17269659). {ECO:0000250|UniProtKB:P10103,
CC ECO:0000269|PubMed:14532127, ECO:0000269|PubMed:17269659}.
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:22105604,
CC ECO:0000269|PubMed:22869893, ECO:0000269|PubMed:24551219, ECO:0000305}.
CC -!- PTM: Poly-ADP-ribosylated by PARP1 when secreted following stimulation
CC with LPS. {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. Can be proteolytically cleaved by a
CC thrombin:thrombomodulin complex; reduces binding to heparin and pro-
CC inflammatory activities (By similarity). {ECO:0000250|UniProtKB:P09429,
CC ECO:0000250|UniProtKB:P10103}.
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.
CC {ECO:0000250|UniProtKB:P09429}.
CC -!- SIMILARITY: Belongs to the HMGB family. {ECO:0000305}.
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DR EMBL; M64986; AAA40729.1; -; mRNA.
DR EMBL; Y00463; CAA68526.1; -; mRNA.
DR EMBL; AF275734; AAF82799.1; -; mRNA.
DR EMBL; BC061779; AAH61779.1; -; mRNA.
DR EMBL; BC081839; AAH81839.1; -; mRNA.
DR EMBL; BC088402; AAH88402.1; -; mRNA.
DR PIR; A41175; NSRTH1.
DR RefSeq; NP_037095.1; NM_012963.2.
DR PDB; 1AAB; NMR; -; A=2-84.
DR PDB; 1CKT; X-ray; 2.50 A; A=8-78.
DR PDB; 1HME; NMR; -; A=89-165.
DR PDB; 1HMF; NMR; -; A=89-165.
DR PDB; 2GZK; NMR; -; A=82-165.
DR PDB; 4QR9; X-ray; 2.00 A; A/B=8-81.
DR PDBsum; 1AAB; -.
DR PDBsum; 1CKT; -.
DR PDBsum; 1HME; -.
DR PDBsum; 1HMF; -.
DR PDBsum; 2GZK; -.
DR PDBsum; 4QR9; -.
DR AlphaFoldDB; P63159; -.
DR SMR; P63159; -.
DR BioGRID; 247493; 7.
DR IntAct; P63159; 2.
DR STRING; 10116.ENSRNOP00000040874; -.
DR MoonProt; P63159; -.
DR CarbonylDB; P63159; -.
DR iPTMnet; P63159; -.
DR jPOST; P63159; -.
DR PaxDb; P63159; -.
DR PRIDE; P63159; -.
DR ABCD; P63159; 4 sequenced antibodies.
DR GeneID; 25459; -.
DR KEGG; rno:25459; -.
DR CTD; 3146; -.
DR RGD; 2802; Hmgb1.
DR eggNOG; KOG0381; Eukaryota.
DR InParanoid; P63159; -.
DR OrthoDB; 1641977at2759; -.
DR PhylomeDB; P63159; -.
DR EvolutionaryTrace; P63159; -.
DR PRO; PR:P63159; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0035868; C:alphav-beta3 integrin-HMGB1 complex; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0000793; C:condensed chromosome; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:CAFA.
DR GO; GO:0005769; C:early endosome; ISO:RGD.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:CAFA.
DR GO; GO:0043005; C:neuron projection; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0017053; C:transcription repressor complex; ISO:RGD.
DR GO; GO:0008097; F:5S rRNA binding; IDA:RGD.
DR GO; GO:0003681; F:bent DNA binding; IDA:MGI.
DR GO; GO:0000405; F:bubble DNA binding; ISS:AgBase.
DR GO; GO:0019958; F:C-X-C chemokine binding; ISO:RGD.
DR GO; GO:0010858; F:calcium-dependent protein kinase regulator activity; ISO:RGD.
DR GO; GO:0000402; F:crossed form four-way junction DNA binding; IDA:MGI.
DR GO; GO:0005125; F:cytokine activity; IDA:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; ISO:RGD.
DR GO; GO:0008301; F:DNA binding, bending; IDA:RGD.
DR GO; GO:0070182; F:DNA polymerase binding; ISO:RGD.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:RGD.
DR GO; GO:0000400; F:four-way junction DNA binding; IDA:RGD.
DR GO; GO:0051861; F:glycolipid binding; IDA:RGD.
DR GO; GO:0008201; F:heparin binding; IDA:RGD.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
DR GO; GO:0001530; F:lipopolysaccharide binding; ISO:RGD.
DR GO; GO:0016829; F:lyase activity; ISO:RGD.
DR GO; GO:0000401; F:open form four-way junction DNA binding; IDA:MGI.
DR GO; GO:0042277; F:peptide binding; IDA:RGD.
DR GO; GO:0001786; F:phosphatidylserine binding; ISO:RGD.
DR GO; GO:0030295; F:protein kinase activator activity; ISO:RGD.
DR GO; GO:0050786; F:RAGE receptor binding; IMP:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:RGD.
DR GO; GO:0003727; F:single-stranded RNA binding; ISO:RGD.
DR GO; GO:0097100; F:supercoiled DNA binding; ISS:AgBase.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:RGD.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:RGD.
DR GO; GO:0002218; P:activation of innate immune response; ISO:RGD.
DR GO; GO:0043277; P:apoptotic cell clearance; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0006284; P:base-excision repair; ISO:RGD.
DR GO; GO:0000902; P:cell morphogenesis; IMP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0098761; P:cellular response to interleukin-7; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0006935; P:chemotaxis; IDA:RGD.
DR GO; GO:0031497; P:chromatin assembly; ISO:RGD.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0032392; P:DNA geometric change; IDA:MGI.
DR GO; GO:0035767; P:endothelial cell chemotaxis; ISO:RGD.
DR GO; GO:0001935; P:endothelial cell proliferation; ISO:RGD.
DR GO; GO:0001654; P:eye development; ISO:RGD.
DR GO; GO:0031507; P:heterochromatin assembly; ISO:RGD.
DR GO; GO:0050930; P:induction of positive chemotaxis; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; ISO:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0002281; P:macrophage activation involved in immune response; ISO:RGD.
DR GO; GO:0050831; P:male-specific defense response to bacterium; IDA:RGD.
DR GO; GO:0001773; P:myeloid dendritic cell activation; ISO:RGD.
DR GO; GO:0051450; P:myoblast proliferation; IMP:RGD.
DR GO; GO:2000426; P:negative regulation of apoptotic cell clearance; ISO:RGD.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:0043371; P:negative regulation of CD4-positive, alpha-beta T cell differentiation; ISO:RGD.
DR GO; GO:0008156; P:negative regulation of DNA replication; IDA:RGD.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; ISO:RGD.
DR GO; GO:0017055; P:negative regulation of RNA polymerase II transcription preinitiation complex assembly; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IMP:RGD.
DR GO; GO:0031175; P:neuron projection development; IGI:UniProtKB.
DR GO; GO:0097350; P:neutrophil clearance; ISS:UniProtKB.
DR GO; GO:0002270; P:plasmacytoid dendritic cell activation; ISO:RGD.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:RGD.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; IMP:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISO:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:RGD.
DR GO; GO:2001200; P:positive regulation of dendritic cell differentiation; ISO:RGD.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISO:RGD.
DR GO; GO:0051106; P:positive regulation of DNA ligation; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0045819; P:positive regulation of glycogen catabolic process; ISO:RGD.
DR GO; GO:0045089; P:positive regulation of innate immune response; ISO:RGD.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISO:RGD.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISO:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:0032732; P:positive regulation of interleukin-1 production; IDA:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:RGD.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:RGD.
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:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:RGD.
DR GO; GO:0071642; P:positive regulation of macrophage inflammatory protein 1 alpha production; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IDA:MGI.
DR GO; GO:0032425; P:positive regulation of mismatch repair; ISO:RGD.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IDA:MGI.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; ISO:RGD.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; ISO:RGD.
DR GO; GO:0033034; P:positive regulation of myeloid cell apoptotic process; IDA:RGD.
DR GO; GO:0045639; P:positive regulation of myeloid cell differentiation; ISO:RGD.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; IMP:RGD.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISO:RGD.
DR GO; GO:0034137; P:positive regulation of toll-like receptor 2 signaling pathway; ISO:RGD.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; ISO:RGD.
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; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0090303; P:positive regulation of wound healing; ISO:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:RGD.
DR GO; GO:0050727; P:regulation of inflammatory response; IDA:RGD.
DR GO; GO:2000819; P:regulation of nucleotide-excision repair; ISO:RGD.
DR GO; GO:0032072; P:regulation of restriction endodeoxyribonuclease activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0051384; P:response to glucocorticoid; ISO:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0009408; P:response to heat; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0034341; P:response to interferon-gamma; IMP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0035711; P:T-helper 1 cell activation; ISO:RGD.
DR GO; GO:0045063; P:T-helper 1 cell differentiation; ISO:RGD.
DR GO; GO:0033151; P:V(D)J recombination; ISO:RGD.
DR DisProt; DP02138; -.
DR Gene3D; 1.10.30.10; -; 2.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR017967; HMG_boxA_CS.
DR InterPro; IPR031076; HMGB1.
DR PANTHER; PTHR48112:SF4; PTHR48112:SF4; 1.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF09011; HMG_box_2; 1.
DR SMART; SM00398; HMG; 2.
DR SUPFAM; SSF47095; SSF47095; 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; Endosome; Heparin-binding; Immunity;
KW Inflammatory response; Innate immunity; Isopeptide bond; Membrane; Nucleus;
KW Oxidation; Phosphoprotein; Reference proteome; Repeat; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2461949"
FT CHAIN 2..215
FT /note="High mobility group protein B1"
FT /id="PRO_0000048530"
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 2..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:0000250|UniProtKB:P09429"
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:0000250|UniProtKB:P09429"
FT REGION 89..108
FT /note="Cytokine-stimulating activity"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT REGION 150..183
FT /note="Binding to AGER/RAGE"
FT /evidence="ECO:0000269|PubMed:12183440"
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:0000269|PubMed:14532127"
FT MOTIF 178..184
FT /note="Nuclear localization signal (NLS) 2"
FT /evidence="ECO:0000269|PubMed:14532127"
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 2..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:0000250|UniProtKB:P09429"
FT MOD_RES 3
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17269659"
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:0000305|PubMed:22869893"
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:0000250|UniProtKB:P10103"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09429"
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:0000305|PubMed:22869893"
FT MOD_RES 90
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P63158"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT MOD_RES 106
FT /note="Cysteine sulfonic acid (-SO3H)"
FT /evidence="ECO:0000305|PubMed:22869893"
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:0000250|UniProtKB:P09429"
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:0000269|PubMed:16962095,
FT ECO:0000269|PubMed:22869893, ECO:0000269|PubMed:24551219"
FT CROSSLNK 28
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT CROSSLNK 43
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT CROSSLNK 44
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT CROSSLNK 68
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT CROSSLNK 180
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT CROSSLNK 182
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT CROSSLNK 183
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT CROSSLNK 184
FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain
FT with Q-?)"
FT /evidence="ECO:0000250|UniProtKB:P09429"
FT MUTAGEN 23
FT /note="C->S: No effect on nuclear localization. Decreases
FT interaction with BCN1 and impairs in autophagy induction.
FT Abolishes cytokine-stimulating activity and no effect on
FT chemoattractant activity; when associated with S-45."
FT /evidence="ECO:0000269|PubMed:16962095,
FT ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:22869893"
FT MUTAGEN 28..30
FT /note="KKK->AAA: Partial cytoplasmic localization; when
FT associated with 181-A--A-183."
FT /evidence="ECO:0000269|PubMed:14532127"
FT MUTAGEN 28..30
FT /note="KKK->QQQ: Partial cytoplasmic localization (mimicks
FT acetylation); when associated with 181-Q--Q-183."
FT /evidence="ECO:0000269|PubMed:14532127"
FT MUTAGEN 38
FT /note="F->A: Disrupts association with chromatin; when
FT associated A-103 and A-122."
FT /evidence="ECO:0000269|PubMed:15808513"
FT MUTAGEN 45
FT /note="C->A: Reduces TNF-stimulating activity."
FT /evidence="ECO:0000269|PubMed:22105604"
FT MUTAGEN 45
FT /note="C->S: No effect on nuclear localization. Decreases
FT interaction with BCN1 and impairs autophagy induction.
FT Abolishes cytokine-stimulating activity and no effect on
FT chemoattractant activity; when associated with S-23."
FT /evidence="ECO:0000269|PubMed:16962095,
FT ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:22869893"
FT MUTAGEN 103
FT /note="F->A: Disrupts association with chromatin; when
FT associated A-38 and A-122."
FT /evidence="ECO:0000269|PubMed:15808513"
FT MUTAGEN 106
FT /note="C->A: Disrupts interaction with TLR4:LY96 receptor
FT complex and abolishes TNF release from macrophages."
FT /evidence="ECO:0000269|PubMed:20547845"
FT MUTAGEN 106
FT /note="C->S: Abolishes cytokine-stimulating activity; no
FT effect on chemoattractant activity; impaired nuclear and
FT enhanced cytoplasmic localization, retained activity in
FT autophagy regulation."
FT /evidence="ECO:0000269|PubMed:16962095,
FT ECO:0000269|PubMed:20819940, ECO:0000269|PubMed:22869893"
FT MUTAGEN 122
FT /note="I->A: Disrupts association with chromatin; when
FT associated A-38 and A-103."
FT /evidence="ECO:0000269|PubMed:15808513"
FT MUTAGEN 182..184
FT /note="KKK->AAA: Partial cytoplasmic localization; when
FT associated with 27-A--A-29."
FT /evidence="ECO:0000269|PubMed:14532127"
FT MUTAGEN 182..184
FT /note="KKK->QQQ: Partial cytoplasmic localization (mimicks
FT acetylation); when associated with 27-Q--Q-29."
FT /evidence="ECO:0000269|PubMed:14532127"
FT HELIX 15..30
FT /evidence="ECO:0007829|PDB:4QR9"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:1AAB"
FT HELIX 38..51
FT /evidence="ECO:0007829|PDB:4QR9"
FT HELIX 54..76
FT /evidence="ECO:0007829|PDB:4QR9"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:2GZK"
FT HELIX 103..116
FT /evidence="ECO:0007829|PDB:1HME"
FT HELIX 122..135
FT /evidence="ECO:0007829|PDB:1HME"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:1HME"
FT HELIX 142..159
FT /evidence="ECO:0007829|PDB:1HME"
SQ SEQUENCE 215 AA; 24894 MW; 8A868DE266D552B5 CRC64;
MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKKCSERWK TMSAKEKGKF
EDMAKADKAR YEREMKTYIP PKGETKKKFK DPNAPKRPPS AFFLFCSEYR PKIKGEHPGL
SIGDVAKKLG EMWNNTAADD KQPYEKKAAK LKEKYEKDIA AYRAKGKPDA AKKGVVKAEK
SKKKKEEEDD EEDEEDEEEE EEEEDEDEEE DDDDE
