HMGB1_BOVIN
ID HMGB1_BOVIN Reviewed; 215 AA.
AC P10103; A5D9G8; Q3ZC39;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=High mobility group protein B1;
DE AltName: Full=High mobility group protein 1;
DE Short=HMG-1;
GN Name=HMGB1; Synonyms=HMG1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Holstein; TISSUE=Fetal thymus;
RX PubMed=3194213; DOI=10.1093/nar/16.21.10375;
RA Kaplan D.J., Duncan C.H.;
RT "Full length cDNA sequence for bovine high mobility group 1 (HMG1)
RT protein.";
RL Nucleic Acids Res. 16:10375-10375(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 116-215.
RX PubMed=6141822; DOI=10.1007/bf01120823;
RA Pentecost B., Dixon G.H.;
RT "Isolation and partial sequence of bovine cDNA clones for the high-
RT mobility-group protein (HMG-1).";
RL Biosci. Rep. 4:49-57(1984).
RN [5]
RP PROTEIN SEQUENCE OF 2-38; 46-157 AND 159-195.
RX PubMed=7202717; DOI=10.1016/0014-5793(80)80453-4;
RA Walker J.M., Gooderham K., Hastings J.R., Mayes E., Johns E.W.;
RT "The primary structures of non-histone chromosomal proteins HMG 1 and 2.";
RL FEBS Lett. 122:264-270(1980).
RN [6]
RP PROTEIN SEQUENCE OF 2-37.
RX PubMed=2365081; DOI=10.1016/0014-5793(90)80308-6;
RA Christen T., Bischoff M., Hobi R., Kuenzle C.C.;
RT "High mobility group proteins 1 and 2 bind preferentially to brominated
RT poly(dG-dC).poly(dG-dC) in the Z-DNA conformation but not to other types of
RT Z-DNA.";
RL FEBS Lett. 267:139-141(1990).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=7409193; DOI=10.1016/0014-5793(80)81219-1;
RA Itkes A.V., Glotov B.O., Nikolaev L.G., Severin E.S.;
RT "Clusters of nonhistone chromosomal protein HMG1 molecules in intact
RT chromatin.";
RL FEBS Lett. 118:63-66(1980).
RN [8]
RP ACETYLATION AT LYS-3; LYS-7; LYS-8; LYS-12; LYS-28; LYS-29; LYS-30;
RP LYS-127; LYS-128; LYS-172; LYS-173; LYS-177; LYS-180; LYS-182; LYS-183;
RP LYS-184 AND LYS-185.
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 [9]
RP FUNCTION.
RX PubMed=16966386; DOI=10.1189/jlb.0306180;
RA Yang D., Chen Q., Yang H., Tracey K.J., Bustin M., Oppenheim J.J.;
RT "High mobility group box-1 protein induces the migration and activation of
RT human dendritic cells and acts as an alarmin.";
RL J. Leukoc. Biol. 81:59-66(2007).
RN [10]
RP FUNCTION, AND INTERACTION WITH AGER.
RX PubMed=17417641; DOI=10.1038/ni1457;
RA Tian J., Avalos A.M., Mao S.Y., Chen B., Senthil K., Wu H., Parroche P.,
RA Drabic S., Golenbock D., Sirois C., Hua J., An L.L., Audoly L., La Rosa G.,
RA Bierhaus A., Naworth P., Marshak-Rothstein A., Crow M.K., Fitzgerald K.A.,
RA Latz E., Kiener P.A., Coyle A.J.;
RT "Toll-like receptor 9-dependent activation by DNA-containing immune
RT complexes is mediated by HMGB1 and RAGE.";
RL Nat. Immunol. 8:487-496(2007).
RN [11]
RP FUNCTION.
RX PubMed=20014975; DOI=10.3109/08916930903384591;
RA Avalos A.M., Kiefer K., Tian J., Christensen S., Shlomchik M., Coyle A.J.,
RA Marshak-Rothstein A.;
RT "RAGE-independent autoreactive B cell activation in response to chromatin
RT and HMGB1/DNA immune complexes.";
RL Autoimmunity 43:103-110(2010).
RN [12]
RP HEPARIN-BINDING, AND CLEAVAGE BY THROMBIN:THROMBOMODULIN.
RX PubMed=18599803; DOI=10.1161/atvbaha.107.150631;
RA Ito T., Kawahara K., Okamoto K., Yamada S., Yasuda M., Imaizumi H.,
RA Nawa Y., Meng X., Shrestha B., Hashiguchi T., Maruyama I.;
RT "Proteolytic cleavage of high mobility group box 1 protein by thrombin-
RT thrombomodulin complexes.";
RL Arterioscler. Thromb. Vasc. Biol. 28:1825-1830(2008).
RN [13]
RP FUNCTION.
RX PubMed=22941653; DOI=10.1093/nar/gks815;
RA Joshi S.R., Sarpong Y.C., Peterson R.C., Scovell W.M.;
RT "Nucleosome dynamics: HMGB1 relaxes canonical nucleosome structure to
RT facilitate estrogen receptor binding.";
RL Nucleic Acids Res. 40:10161-10171(2012).
RN [14]
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 [15]
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 [16]
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 [17]
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).
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. Bound to RAGE mediates signaling for neuronal
CC outgrowth. May play a role in accumulation of expanded polyglutamine
CC (polyQ) proteins (By similarity). {ECO:0000250|UniProtKB:P09429,
CC ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159,
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. 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 Involved in V(D)J recombination by acting as a cofactor of the RAG
CC complex: acts by stimulating cleavage and RAG protein binding at the 23
CC bp spacer of conserved recombination signal sequences (RSS) (By
CC similarity). In vitro can displace histone H1 from highly bent DNA. Can
CC restructure the canonical nucleosome leading to relaxation of
CC structural constraints for transcription factor-binding
CC (PubMed:22941653). Enhances binding of sterol regulatory element-
CC binding proteins (SREBPs) such as SREBF1 to their cognate DNA sequences
CC and increases their transcriptional activities. Facilitates binding of
CC TP53 to DNA. May be involved in mitochondrial quality control and
CC autophagy in a transcription-dependent fashion implicating HSPB1. Can
CC modulate the activity of the telomerase complex and may be involved in
CC telomere maintenance (By similarity). {ECO:0000250|UniProtKB:P09429,
CC ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159,
CC ECO:0000269|PubMed:22941653}.
CC -!- FUNCTION: In the cytoplasm proposed to dissociate the BECN1:BCL2
CC complex via competitive interaction with BECN1 leading to autophagy
CC activation. Involved in oxidative stress-mediated autophagy. Can
CC protect BECN1 and ATG5 from calpain-mediated cleavage and thus proposed
CC to control their proautophagic and proapoptotic functions and to
CC regulate the extent and severity of inflammation-associated cellular
CC injury. In myeloid cells has a protective role against endotoxemia and
CC bacterial infection by promoting autophagy. 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 inflammatory
CC response. Fully reduced HGMB1 (which subsequently gets oxidized after
CC release) in association with CXCL12 mediates the recruitment of
CC inflammatory cells during the initial phase of tissue injury; the
CC CXCL12:HMGB1 complex triggers CXCR4 homodimerization (By similarity).
CC Induces the migration of monocyte-derived immature dendritic cells and
CC seems to regulate adhesive and migratory functions of neutrophils
CC implicating AGER/RAGE and ITGAM (PubMed:16966386). Can bind to various
CC types of DNA and RNA including microbial unmethylated CpG-DNA to
CC enhance the innate immune response to nucleic acids. Proposed to act in
CC promiscuous DNA/RNA sensing which cooperates with subsequent
CC discriminative sensing by specific pattern recognition receptors.
CC Promotes extracellular DNA-induced AIM2 inflammasome activation
CC implicating AGER/RAGE (By similarity). Disulfide HMGB1 binds to
CC transmembrane receptors, such as AGER/RAGE, TLR2, TLR4 and probably
CC TREM1, thus activating their signal transduction pathways
CC (PubMed:17417641). Mediates the release of cytokines/chemokines such as
CC TNF, IL-1, IL-6, IL-8, CCL2, CCL3, CCL4 and CXCL10. Promotes secretion
CC of interferon-gamma by macrophage-stimulated natural killer (NK) cells
CC in concert with other cytokines like IL-2 or IL-12. TLR4 is proposed to
CC be the primary receptor promoting macrophage activation and signaling
CC through TLR4 seems to implicate LY96/MD-2. In bacterial LPS- or LTA-
CC mediated inflammatory responses binds to the endotoxins and transfers
CC them to CD14 for signaling to the respective TLR4:LY96 and TLR2
CC complexes. Contributes to tumor proliferation by association with
CC ACER/RAGE. Can bind to IL1-beta and signals through the IL1R1:IL1RAP
CC receptor complex (By similarity). 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
CC (PubMed:17417641). Via HMGB1-containing chromatin immune complexes may
CC also promote B cell responses to endogenous TLR9 ligands through a B-
CC cell receptor (BCR)-dependent and ACER/RAGE-independent mechanism
CC (PubMed:20014975). Inhibits phagocytosis of apoptotic cells by
CC macrophages; the function is dependent on poly-ADP-ribosylation and
CC involves binding to phosphatidylserine on the cell surface of apoptotic
CC cells. In adaptive immunity may be involved in enhancing immunity
CC through activation of effector T-cells and suppression of regulatory T
CC (TReg) cells. In contrast, without implicating effector or regulatory
CC T-cells, required for tumor infiltration and activation of T-cells
CC expressing the lymphotoxin LTA:LTB heterotrimer thus promoting tumor
CC malignant progression. Also reported to limit proliferation of T-cells.
CC Released HMGB1:nucleosome complexes formed during apoptosis can signal
CC through TLR2 to induce cytokine production. Involved in induction of
CC immunological tolerance by apoptotic cells; its pro-inflammatory
CC activities when released by apoptotic cells are neutralized by reactive
CC oxygen species (ROS)-dependent oxidation specifically on Cys-106.
CC During macrophage activation by activated lymphocyte-derived self
CC apoptotic DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes
CC (By similarity). {ECO:0000250|UniProtKB:P09429,
CC ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159,
CC ECO:0000269|PubMed:16966386, ECO:0000269|PubMed:17417641,
CC ECO:0000269|PubMed:20014975}.
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. Associates with the TLR4:LY96
CC receptor complex. Component of the RAG complex composed of core
CC components RAG1 and RAG2, and associated component HMGB1 or HMGB2.
CC Interacts (in cytoplasm upon starvation) with BECN1; inhibits the
CC interaction of BECN1 and BCL2 leading to promotion of autophagy.
CC Interacts with KPNA1; involved in nuclear import (By similarity).
CC Interacts with AGER (PubMed:17417641). Interacts with SREBF1, TLR2,
CC TLR4, TLR9, PTPRZ1, APEX1, FEN1, POLB, TERT. Interacts with IL1B, MSH2,
CC XPA, XPC, HNF1A, TP53. Interacts with CD24; the probable CD24:SIGLEC10
CC complex is proposed to inhibit HGMB1-mediated tissue damage immune
CC response. Interacts with THBD; prevents HGMB1 interaction with
CC ACER/RAGE and inhibits HGMB1 pro-inflammatory activity. Interacts with
CC HAVCR2; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate
CC immune response. Interacts with XPO1; mediating nuclear export (By
CC similarity). {ECO:0000250|UniProtKB:P09429,
CC ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:7409193}. Chromosome
CC {ECO:0000269|PubMed:7409193}. Cytoplasm {ECO:0000250|UniProtKB:P09429}.
CC Secreted {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P63158}.
CC Cell membrane {ECO:0000250|UniProtKB:P09429,
CC ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159}; Peripheral
CC membrane protein {ECO:0000250|UniProtKB:P09429,
CC ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159};
CC Extracellular side {ECO:0000250|UniProtKB:P09429,
CC ECO:0000250|UniProtKB:P63158, ECO:0000250|UniProtKB:P63159}. Endosome
CC {ECO:0000250|UniProtKB:P63158}. Endoplasmic reticulum-Golgi
CC intermediate compartment {ECO:0000250|UniProtKB:P63158}. Note=In basal
CC state predominantly nuclear. Shuttles between the cytoplasm and the
CC nucleus. Translocates from the nucleus to the cytoplasm upon autophagy
CC stimulation. Release from macrophages in the extracellular milieu
CC 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 HGMB1 which
CC subsequently gets oxidized. Also released from apoptotic cells. Active
CC secretion from a variety of immune and non-immune cells such as
CC macrophages, monocytes, neutrophils, dendritic cells, natural killer
CC cells and plasma cells in response to various stimuli such as LPS and
CC cytokines involves a nonconventional secretory process via secretory
CC lysosomes. Found on the surface of activated platelets.
CC {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P63158}.
CC -!- DOMAIN: HMG box 2 mediates pro-inflammatory cytokine-stimulating
CC activity and binding to TLR4. However, not involved in mediating
CC immunogenic activity in the context of apoptosis-induced immune
CC tolerance. {ECO:0000250|UniProtKB:P09429}.
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:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P63159}.
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.
CC Acetylation on lysine residues in the nuclear localization signals (NLS
CC 1 and NLS 2) leads to cytoplasmic localization and subsequent secretion
CC (PubMed:14532127). Acetylation on Lys-3 results in preferential binding
CC to DNA ends and impairs DNA bending activity (By similarity).
CC {ECO:0000250|UniProtKB:P63159, ECO:0000269|PubMed:14532127}.
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:0000250|UniProtKB:P09429}.
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 (By similarity). Can be
CC proteolytically cleaved by a thrombin:thrombomodulin complex; reduces
CC binding to heparin and pro-inflammatory activities.
CC {ECO:0000250|UniProtKB:P09429, ECO:0000269|PubMed:18599803}.
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; X12796; CAA31284.1; -; mRNA.
DR EMBL; BT030587; ABQ13027.1; -; mRNA.
DR EMBL; BC102929; AAI02930.1; -; mRNA.
DR EMBL; M26110; AAA30567.1; -; mRNA.
DR PIR; S01947; S01947.
DR RefSeq; NP_788785.1; NM_176612.1.
DR RefSeq; XP_005213615.1; XM_005213558.1.
DR RefSeq; XP_010808966.1; XM_010810664.2.
DR AlphaFoldDB; P10103; -.
DR SMR; P10103; -.
DR CORUM; P10103; -.
DR STRING; 9913.ENSBTAP00000024094; -.
DR iPTMnet; P10103; -.
DR PaxDb; P10103; -.
DR PeptideAtlas; P10103; -.
DR PRIDE; P10103; -.
DR ABCD; P10103; 2 sequenced antibodies.
DR Ensembl; ENSBTAT00000024094; ENSBTAP00000024094; ENSBTAG00000018103.
DR GeneID; 282691; -.
DR KEGG; bta:282691; -.
DR CTD; 3146; -.
DR VEuPathDB; HostDB:ENSBTAG00000018103; -.
DR VGNC; VGNC:53816; HMGB1.
DR eggNOG; KOG0381; Eukaryota.
DR GeneTree; ENSGT00950000183120; -.
DR HOGENOM; CLU_082854_0_0_1; -.
DR InParanoid; P10103; -.
DR OMA; GEMWNSK; -.
DR OrthoDB; 1641977at2759; -.
DR TreeFam; TF105371; -.
DR Reactome; R-BTA-140342; Apoptosis induced DNA fragmentation.
DR Reactome; R-BTA-5620971; Pyroptosis.
DR Reactome; R-BTA-5686938; Regulation of TLR by endogenous ligand.
DR Reactome; R-BTA-6798695; Neutrophil degranulation.
DR Proteomes; UP000009136; Chromosome 12.
DR Bgee; ENSBTAG00000018103; Expressed in pharyngeal tonsil and 106 other tissues.
DR GO; GO:0000785; C:chromatin; ISS:AgBase.
DR GO; GO:0000793; C:condensed chromosome; ISS:AgBase.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000405; F:bubble DNA binding; ISS:AgBase.
DR GO; GO:0042056; F:chemoattractant activity; IDA:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB.
DR GO; GO:0008301; F:DNA binding, bending; IDA:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0000400; F:four-way junction DNA binding; ISS:AgBase.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0044378; F:non-sequence-specific DNA binding, bending; ISS:AgBase.
DR GO; GO:0050786; F:RAGE receptor binding; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0097100; F:supercoiled DNA binding; ISS:AgBase.
DR GO; GO:0045322; F:unmethylated CpG binding; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0043277; P:apoptotic cell clearance; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0002322; P:B cell proliferation involved in immune response; IDA:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; NAS:UniProtKB.
DR GO; GO:0002407; P:dendritic cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0032392; P:DNA geometric change; ISS:AgBase.
DR GO; GO:0006310; P:DNA recombination; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0006265; P:DNA topological change; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0001773; P:myeloid dendritic cell activation; IDA:UniProtKB.
DR GO; GO:0017055; P:negative regulation of RNA polymerase II transcription preinitiation complex assembly; ISS:AgBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:AgBase.
DR GO; GO:0097350; P:neutrophil clearance; ISS:UniProtKB.
DR GO; GO:0006334; P:nucleosome assembly; ISS:AgBase.
DR GO; GO:0002270; P:plasmacytoid dendritic cell activation; IDA:UniProtKB.
DR GO; GO:0051106; P:positive regulation of DNA ligation; ISS:UniProtKB.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; IMP:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0002840; P:regulation of T cell mediated immune response to tumor cell; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; IDA:UniProtKB.
DR GO; GO:0033151; P:V(D)J recombination; IDA:UniProtKB.
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 Acetylation; Adaptive immunity; ADP-ribosylation; Autophagy; Cell membrane;
KW Chemotaxis; Chromosome; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; DNA damage; DNA recombination; DNA repair; DNA-binding;
KW Endosome; Immunity; Inflammatory response; Innate immunity;
KW Isopeptide bond; Membrane; Nucleus; Oxidation; Phosphoprotein;
KW Reference proteome; Repeat; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2365081,
FT ECO:0000269|PubMed:7202717"
FT CHAIN 2..215
FT /note="High mobility group protein B1"
FT /id="PRO_0000048523"
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: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 2..10
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000269|PubMed:18599803"
FT SITE 10..11
FT /note="Cleavage; by thrombin:thrombomodulin"
FT /evidence="ECO:0000269|PubMed:18599803"
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:14532127"
FT MOD_RES 7
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
FT MOD_RES 8
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
FT MOD_RES 12
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
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:0000269|PubMed:14532127"
FT MOD_RES 29
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
FT MOD_RES 30
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
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: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:0000250|UniProtKB:P09429"
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:0000269|PubMed:14532127"
FT MOD_RES 128
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
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:0000269|PubMed:14532127"
FT MOD_RES 173
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
FT MOD_RES 177
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
FT MOD_RES 180
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
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:0000269|PubMed:14532127"
FT MOD_RES 183
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
FT MOD_RES 184
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
FT MOD_RES 185
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:14532127"
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: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 CONFLICT 23
FT /note="C -> S (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="C -> A (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 116..120
FT /note="EHPGL -> PGGGV (in Ref. 4; AAA30567)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="E -> D (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 215 AA; 24908 MW; 8BC38CF277D417B5 CRC64;
MGKGDPKKPR GKMSSYAFFV QTCREEHKKK HPDASVNFSE FSKKCSERWK TMSAKEKGKF
EDMAKADKAR YEREMKTYIP PKGETKKKFK DPNAPKRPPS AFFLFCSEYR PKIKGEHPGL
SIGDVAKKLG EMWNNTAADD KQPYEKKAAK LKEKYEKDIA AYRAKGKPDA AKKGVVKAEK
SKKKKEEEED EEDEEDEEEE EDEEDEEEEE DDDDE
