Full text data of HMGB1
HMGB1
(HMG1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
High mobility group protein B1 (High mobility group protein 1; HMG-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
High mobility group protein B1 (High mobility group protein 1; HMG-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00219096
IPI00219096 High mobility group protein 1 - AMIGO2 protein (Amphoterin) High mobility group protein 1 - AMIGO2 protein (Amphoterin) membrane n/a n/a n/a 1 n/a n/a n/a 1 4 n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a integral membrane protein n/a expected molecular weight found in band > 188 kDa together with ubiquitin
IPI00219096 High mobility group protein 1 - AMIGO2 protein (Amphoterin) High mobility group protein 1 - AMIGO2 protein (Amphoterin) membrane n/a n/a n/a 1 n/a n/a n/a 1 4 n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a integral membrane protein n/a expected molecular weight found in band > 188 kDa together with ubiquitin
UniProt
P09429
ID HMGB1_HUMAN Reviewed; 215 AA.
AC P09429; A5D8W9; Q14321; Q5T7C3; Q6IBE1;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 153.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT protein 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
RT (HMG1) 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.,
RA Igarashi H., 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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
RT 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.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA 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.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA 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.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Simpson R.J., 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
RT lineage kinase MLK2.";
RL Electrophoresis 18:588-598(1997).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 AND SER-100, AND MASS
RP SPECTROMETRY.
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 [16]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-112, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18655026; DOI=10.1002/pmic.200700887;
RA Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E.,
RA Wu J., Luo Y., Qiang B., Yuan J., Sun X., Peng X.;
RT "Proteomic analysis of ubiquitinated proteins in normal hepatocyte
RT cell line Chang liver cells.";
RL Proteomics 8:2885-2896(2008).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-30, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
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.,
RA Buerckstuemmer T., 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
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 [22]
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
RT mobility group protein B1.";
RL Submitted (FEB-2008) to the PDB data bank.
CC -!- FUNCTION: DNA binding proteins that associates with chromatin and
CC has the ability to bend DNA. Binds preferentially single-stranded
CC DNA. Involved in V(D)J recombination by acting as a cofactor of
CC the RAG complex. Acts by stimulating cleavage and RAG protein
CC binding at the 23 bp spacer of conserved recombination signal
CC sequences (RSS). Heparin-binding protein that has a role in the
CC extension of neurite-type cytoplasmic processes in developing
CC cells (By similarity).
CC -!- SUBUNIT: Component of the RAG complex composed of core components
CC RAG1 and RAG2, and associated component HMGB1 or HMGB2 (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome.
CC -!- SIMILARITY: Belongs to the HMGB family.
CC -!- SIMILARITY: Contains 2 HMG box DNA-binding domains.
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; CAI15600.1; -; 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 PIR; S02826; S02826.
DR RefSeq; NP_002119.1; NM_002128.4.
DR RefSeq; XP_005266420.1; XM_005266363.1.
DR RefSeq; XP_005266421.1; XM_005266364.1.
DR RefSeq; XP_005266422.1; XM_005266365.1.
DR RefSeq; XP_005266423.1; XM_005266366.1.
DR RefSeq; XP_005266424.1; XM_005266367.1.
DR UniGene; Hs.434102; -.
DR UniGene; Hs.593339; -.
DR UniGene; Hs.596078; -.
DR PDB; 2LY4; NMR; -; A=2-84.
DR PDB; 2YRQ; NMR; -; A=1-166.
DR PDBsum; 2LY4; -.
DR PDBsum; 2YRQ; -.
DR ProteinModelPortal; P09429; -.
DR SMR; P09429; 5-166.
DR DIP; DIP-24195N; -.
DR IntAct; P09429; 19.
DR MINT; MINT-153055; -.
DR STRING; 9606.ENSP00000343040; -.
DR ChEMBL; CHEMBL2311236; -.
DR PhosphoSite; P09429; -.
DR DMDM; 123369; -.
DR DOSAC-COBS-2DPAGE; P09429; -.
DR PaxDb; P09429; -.
DR PeptideAtlas; P09429; -.
DR PRIDE; P09429; -.
DR DNASU; 3146; -.
DR Ensembl; ENST00000339872; ENSP00000343040; ENSG00000189403.
DR Ensembl; ENST00000341423; ENSP00000345347; ENSG00000189403.
DR Ensembl; ENST00000399494; ENSP00000382417; ENSG00000189403.
DR Ensembl; ENST00000405805; ENSP00000384678; ENSG00000189403.
DR GeneID; 3146; -.
DR KEGG; hsa:3146; -.
DR UCSC; uc001usx.3; human.
DR CTD; 3146; -.
DR GeneCards; GC13M031032; -.
DR H-InvDB; HIX0030745; -.
DR HGNC; HGNC:4983; HMGB1.
DR HPA; CAB005873; -.
DR HPA; HPA003506; -.
DR MIM; 163905; gene.
DR neXtProt; NX_P09429; -.
DR PharmGKB; PA188; -.
DR eggNOG; COG5648; -.
DR HOGENOM; HOG000197861; -.
DR HOVERGEN; HBG009000; -.
DR InParanoid; P09429; -.
DR KO; K10802; -.
DR OMA; DMGKPPV; -.
DR OrthoDB; EOG7WHHBQ; -.
DR PhylomeDB; P09429; -.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; HMGB1; human.
DR EvolutionaryTrace; P09429; -.
DR GeneWiki; HMGB1; -.
DR GenomeRNAi; 3146; -.
DR NextBio; 12470; -.
DR PRO; PR:P09429; -.
DR ArrayExpress; P09429; -.
DR Bgee; P09429; -.
DR CleanEx; HS_HMGB1; -.
DR Genevestigator; P09429; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0000793; C:condensed chromosome; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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; ISS:UniProtKB.
DR GO; GO:0008301; F:DNA binding, bending; IMP:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0050786; F:RAGE receptor binding; ISS:UniProtKB.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; TAS:Reactome.
DR GO; GO:0006288; P:base-excision repair, DNA ligation; IDA:UniProtKB.
DR GO; GO:0002407; P:dendritic cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0006265; P:DNA topological change; ISS:UniProtKB.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IEP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0001773; P:myeloid dendritic cell activation; ISS:UniProtKB.
DR GO; GO:2000426; P:negative regulation of apoptotic cell clearance; IEA:Ensembl.
DR GO; GO:0017055; P:negative regulation of RNA polymerase II transcriptional preinitiation complex assembly; IDA:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; 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; IPR017967; HMG_boxA_CS.
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; Chromosome; Complete proteome;
KW Direct protein sequencing; DNA-binding; Isopeptide bond; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Ubl conjugation.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 215 High mobility group protein B1.
FT /FTId=PRO_0000048526.
FT DNA_BIND 9 79 HMG box 1.
FT DNA_BIND 95 163 HMG box 2.
FT COMPBIAS 186 215 Asp/Glu-rich (acidic).
FT MOD_RES 30 30 N6-acetyllysine.
FT MOD_RES 35 35 Phosphoserine.
FT MOD_RES 100 100 Phosphoserine.
FT CROSSLNK 112 112 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT VARIANT 11 11 G -> R (in gastric-carcinoma cell line).
FT /FTId=VAR_046451.
FT VARIANT 149 149 A -> E (in gastric-carcinoma cell line).
FT /FTId=VAR_046452.
FT VARIANT 156 156 E -> Q.
FT /FTId=VAR_046453.
FT VARIANT 190 190 D -> G (in gastric-carcinoma cell line).
FT /FTId=VAR_046454.
FT CONFLICT 143 143 P -> H (in Ref. 13; AAI41845).
FT CONFLICT 215 215 E -> D (in Ref. 8; CAG33144).
FT STRAND 6 8
FT HELIX 15 30
FT HELIX 38 50
FT HELIX 54 76
FT STRAND 92 94
FT HELIX 101 116
FT STRAND 118 120
FT HELIX 122 135
FT HELIX 138 140
FT HELIX 141 163
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
//
ID HMGB1_HUMAN Reviewed; 215 AA.
AC P09429; A5D8W9; Q14321; Q5T7C3; Q6IBE1;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 153.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT protein 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
RT (HMG1) 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.,
RA Igarashi H., 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., 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
RT 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.,
RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T.,
RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R.,
RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S.,
RA 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.,
RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J.,
RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E.,
RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L.,
RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J.,
RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S.,
RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J.,
RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M.,
RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A.,
RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S.,
RA 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.,
RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S.,
RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A.,
RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L.,
RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M.,
RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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.,
RA Simpson R.J., 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
RT lineage kinase MLK2.";
RL Electrophoresis 18:588-598(1997).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 AND SER-100, AND MASS
RP SPECTROMETRY.
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 [16]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-112, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18655026; DOI=10.1002/pmic.200700887;
RA Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E.,
RA Wu J., Luo Y., Qiang B., Yuan J., Sun X., Peng X.;
RT "Proteomic analysis of ubiquitinated proteins in normal hepatocyte
RT cell line Chang liver cells.";
RL Proteomics 8:2885-2896(2008).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-30, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
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.,
RA Buerckstuemmer T., 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
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 [22]
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
RT mobility group protein B1.";
RL Submitted (FEB-2008) to the PDB data bank.
CC -!- FUNCTION: DNA binding proteins that associates with chromatin and
CC has the ability to bend DNA. Binds preferentially single-stranded
CC DNA. Involved in V(D)J recombination by acting as a cofactor of
CC the RAG complex. Acts by stimulating cleavage and RAG protein
CC binding at the 23 bp spacer of conserved recombination signal
CC sequences (RSS). Heparin-binding protein that has a role in the
CC extension of neurite-type cytoplasmic processes in developing
CC cells (By similarity).
CC -!- SUBUNIT: Component of the RAG complex composed of core components
CC RAG1 and RAG2, and associated component HMGB1 or HMGB2 (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome.
CC -!- SIMILARITY: Belongs to the HMGB family.
CC -!- SIMILARITY: Contains 2 HMG box DNA-binding domains.
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; CAI15600.1; -; 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 PIR; S02826; S02826.
DR RefSeq; NP_002119.1; NM_002128.4.
DR RefSeq; XP_005266420.1; XM_005266363.1.
DR RefSeq; XP_005266421.1; XM_005266364.1.
DR RefSeq; XP_005266422.1; XM_005266365.1.
DR RefSeq; XP_005266423.1; XM_005266366.1.
DR RefSeq; XP_005266424.1; XM_005266367.1.
DR UniGene; Hs.434102; -.
DR UniGene; Hs.593339; -.
DR UniGene; Hs.596078; -.
DR PDB; 2LY4; NMR; -; A=2-84.
DR PDB; 2YRQ; NMR; -; A=1-166.
DR PDBsum; 2LY4; -.
DR PDBsum; 2YRQ; -.
DR ProteinModelPortal; P09429; -.
DR SMR; P09429; 5-166.
DR DIP; DIP-24195N; -.
DR IntAct; P09429; 19.
DR MINT; MINT-153055; -.
DR STRING; 9606.ENSP00000343040; -.
DR ChEMBL; CHEMBL2311236; -.
DR PhosphoSite; P09429; -.
DR DMDM; 123369; -.
DR DOSAC-COBS-2DPAGE; P09429; -.
DR PaxDb; P09429; -.
DR PeptideAtlas; P09429; -.
DR PRIDE; P09429; -.
DR DNASU; 3146; -.
DR Ensembl; ENST00000339872; ENSP00000343040; ENSG00000189403.
DR Ensembl; ENST00000341423; ENSP00000345347; ENSG00000189403.
DR Ensembl; ENST00000399494; ENSP00000382417; ENSG00000189403.
DR Ensembl; ENST00000405805; ENSP00000384678; ENSG00000189403.
DR GeneID; 3146; -.
DR KEGG; hsa:3146; -.
DR UCSC; uc001usx.3; human.
DR CTD; 3146; -.
DR GeneCards; GC13M031032; -.
DR H-InvDB; HIX0030745; -.
DR HGNC; HGNC:4983; HMGB1.
DR HPA; CAB005873; -.
DR HPA; HPA003506; -.
DR MIM; 163905; gene.
DR neXtProt; NX_P09429; -.
DR PharmGKB; PA188; -.
DR eggNOG; COG5648; -.
DR HOGENOM; HOG000197861; -.
DR HOVERGEN; HBG009000; -.
DR InParanoid; P09429; -.
DR KO; K10802; -.
DR OMA; DMGKPPV; -.
DR OrthoDB; EOG7WHHBQ; -.
DR PhylomeDB; P09429; -.
DR Reactome; REACT_578; Apoptosis.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; HMGB1; human.
DR EvolutionaryTrace; P09429; -.
DR GeneWiki; HMGB1; -.
DR GenomeRNAi; 3146; -.
DR NextBio; 12470; -.
DR PRO; PR:P09429; -.
DR ArrayExpress; P09429; -.
DR Bgee; P09429; -.
DR CleanEx; HS_HMGB1; -.
DR Genevestigator; P09429; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0000793; C:condensed chromosome; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
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; ISS:UniProtKB.
DR GO; GO:0008301; F:DNA binding, bending; IMP:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0050786; F:RAGE receptor binding; ISS:UniProtKB.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0006309; P:apoptotic DNA fragmentation; TAS:Reactome.
DR GO; GO:0006288; P:base-excision repair, DNA ligation; IDA:UniProtKB.
DR GO; GO:0002407; P:dendritic cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0006265; P:DNA topological change; ISS:UniProtKB.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IEP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0001773; P:myeloid dendritic cell activation; ISS:UniProtKB.
DR GO; GO:2000426; P:negative regulation of apoptotic cell clearance; IEA:Ensembl.
DR GO; GO:0017055; P:negative regulation of RNA polymerase II transcriptional preinitiation complex assembly; IDA:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; 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; IPR017967; HMG_boxA_CS.
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; Chromosome; Complete proteome;
KW Direct protein sequencing; DNA-binding; Isopeptide bond; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Ubl conjugation.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 215 High mobility group protein B1.
FT /FTId=PRO_0000048526.
FT DNA_BIND 9 79 HMG box 1.
FT DNA_BIND 95 163 HMG box 2.
FT COMPBIAS 186 215 Asp/Glu-rich (acidic).
FT MOD_RES 30 30 N6-acetyllysine.
FT MOD_RES 35 35 Phosphoserine.
FT MOD_RES 100 100 Phosphoserine.
FT CROSSLNK 112 112 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT VARIANT 11 11 G -> R (in gastric-carcinoma cell line).
FT /FTId=VAR_046451.
FT VARIANT 149 149 A -> E (in gastric-carcinoma cell line).
FT /FTId=VAR_046452.
FT VARIANT 156 156 E -> Q.
FT /FTId=VAR_046453.
FT VARIANT 190 190 D -> G (in gastric-carcinoma cell line).
FT /FTId=VAR_046454.
FT CONFLICT 143 143 P -> H (in Ref. 13; AAI41845).
FT CONFLICT 215 215 E -> D (in Ref. 8; CAG33144).
FT STRAND 6 8
FT HELIX 15 30
FT HELIX 38 50
FT HELIX 54 76
FT STRAND 92 94
FT HELIX 101 116
FT STRAND 118 120
FT HELIX 122 135
FT HELIX 138 140
FT HELIX 141 163
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
//
MIM
163905
*RECORD*
*FIELD* NO
163905
*FIELD* TI
*163905 HIGH MOBILITY GROUP BOX 1; HMGB1
;;HIGH MOBILITY GROUP PROTEIN 1; HMG1;;
CHROMOSOMAL PROTEIN, NONHISTONE, HMG1;;
read moreNONHISTONE CHROMOSOMAL PROTEIN HMG1;;
AMPHOTERIN
*FIELD* TX
CLONING
The HMG (high mobility group) proteins are nonhistone chromosomal
proteins. Wen et al. (1989) isolated a cDNA clone that encodes the
entire 215-amino acid sequence of HMG1 from a human placenta cDNA
library. Northern blot analysis showed that 3 mRNA species of
approximately 1.0, 1.4, and 2.4 kb were expressed in all mammalian
organs and cell lines examined. The HMG1 protein has a molecular mass of
approximately 25 kD.
GENE STRUCTURE
A large number of sequences related to the cDNA for HMG1 protein
hampered the cloning and mapping of the active HMG1 gene. Ferrari et al.
(1996) showed that the HMG1 gene contains introns, whereas the
HMG1-related sequences do not and most likely are retrotransposed
pseudogenes. They identified 8 YACs from the ICI and CEPH libraries that
contain the human HMG1 gene. The gene is similar in structure to the
previously characterized mouse homolog.
MAPPING
Ferrari et al. (1996) mapped the HMG1 gene to chromosome 13q12 by
fluorescence in situ hybridization. The mouse Hmg1 gene maps to the
telomeric region of murine chromosome 5, which has syntenic homology
with human chromosome 13q12.
GENE FUNCTION
High mobility group-1 protein is an abundant component of all mammalian
nuclei, and related proteins exist in all eukaryotes. HMG1 binds with
high affinity to specific DNA structures such as bent or kinked DNA
(Bianchi et al., 1989). It is considered to be a structural protein of
chromatin.
Wang et al. (1999) identified HMG1 as a potential late mediator of
lethality due to endotoxin. HMG1 protein was found to be released by
cultured macrophages more than 8 hours after stimulation with endotoxin,
tumor necrosis factor (TNF; 191160), or interleukin-1 (see 147720). Mice
showed increased serum levels of HMG1 from 8 to 32 hours after endotoxin
exposure. Delayed administration of antibodies to HMG1 attenuated
endotoxin lethality in mice, and administration of HMG1 itself was
lethal. Wang et al. (1999) studied 8 normal subjects and 25 critically
ill septic patients with bacteremia and sepsis-induced organ
dysfunction. HMG1 was not detectable in the serum of normal subjects,
but significant levels were observed in critically ill patients with
sepsis, and these levels were higher in patients who succumbed as
compared to patients with nonlethal infection. The delayed kinetics of
HMG1 release suggested that serum HMG1 levels may be a convenient marker
of disease severity. Moreover, the observations that HMG1 itself is
toxic and that anti-HMG1 prevents lipopolysaccharide lethality, point to
HMG1 as a potential target for therapeutic intervention.
The receptor for advanced glycation end products (RAGE; 600214) is a
central cell surface receptor for HMG1 (amphoterin), a polypeptide
linked to outgrowth of cultured cortical neurons derived from developing
brain. Indeed, the colocalization of RAGE and amphoterin at the leading
edge of advancing neurites indicated their potential contribution to
cellular migration, and in pathologies such as tumor invasion. Taguchi
et al. (2000) demonstrated that blockade of RAGE-amphoterin decreased
growth and metastases of both implanted tumors and tumors developing
spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin
interaction suppressed activation of p44 (601795)/p42 (603441), p38
(600289), and SAP/JNK (601158) MAP kinases, molecular effector
mechanisms linked to tumor proliferation, invasion, and expression of
matrix metalloproteinases.
Zetterstrom et al. (2002) identified HMGB1 as an antibacterial factor
produced and stored intracellularly in the human adenoid gland.
Lotze and Tracey (2005) reviewed the role of HMGB1 as a cytokine
mediating local and systemic responses to necrotic cell death and
cancer, invasion by pathogens, trauma, and sepsis.
Prasad et al. (2007) found that Hmgb1 interacted with stabilized base
excision repair (BER) intermediates in mouse embryonic fibroblasts.
Fluorescence-tagged human HMGB1 accumulated at sites of DNA damage in
HeLa cells, and it stimulated incision activities of APE (APEX; 107748)
and FEN1 (600393) on BER substrates. Coimmunoprecipitation experiments
showed that HMGB1 interacted with BER enzymes. Hmgb1-null mouse
embryonic fibroblasts were less sensitive than wildtype cells to a
methylating agent, probably due to production of fewer strand-break BER
intermediates. Prasad et al. (2007) concluded that HMGB1 is a BER
cofactor that modulates BER capacity.
Using pull-down assays, Yanai et al. (2009) found that mouse HMGB
proteins bound to all immunogenic nucleic acids, with a correlation
between affinity and immunogenicity. Hmgb1 -/- and Hmgb2 (163906) -/-
mouse cells were defective in type I interferon and inflammatory
cytokine induction by DNA or RNA targeted to activate cytosolic nucleic
acid-sensing receptors. Mouse cells in which expression of Hmgb1, Hmgb2,
and Hmgb3 (300193) was suppressed by small interfering RNA also had
impaired activation of transcription factors Irf3 (603734) and Nfkb (see
164011). The lack of HMGBs also resulted in poorer activation of
Toll-like receptor-3 (Tlr3; 603029), Tlr7 (300365), and Tlr9 (605474) by
their cognate nucleic acids (dsRNA, ssRNA, and hypomethylated DNA,
respectively). Yanai et al. (2009) concluded that selective activation
of nucleic acid-sensing receptors is contingent on the more promiscuous
sensing of nucleic acids by HMGBs and may have implications for the
treatment of immunologic disorders.
By studying HMGB1 release mechanisms, Lu et al. (2012) identified a role
for PKR (176871) in inflammasome activation. Exposure of macrophages to
inflammasome agonists induced PKR autophosphorylation. PKR inactivation
by genetic deletion or pharmacologic inhibition severely impaired
inflammasome activation in response to double-stranded RNA, ATP,
monosodium urate, adjuvant aluminum, rotenone, live E. coli, anthrax
lethal toxin, DNA transfection, and S. typhimurium infection. PKR
deficiency significantly inhibited the secretion of IL1-beta (147720),
IL18 (600953), and HMGB1 in E. coli-induced peritonitis. PKR physically
interacts with several inflammasome components, including NLRP3
(606416), NLRP1 (606636), NLRC4 (606831), and AIM2 (604578), and broadly
regulates inflammasome activation. PKR autophosphorylation in a
cell-free system with recombinant NLRP3, ASC (PYCARD; 606838), and
pro-caspase-1 (147678) reconstituted inflammasome activity. Lu et al.
(2012) concluded that their results showed a crucial role for PKR in
inflammasome activation, and indicated that it should be possible to
pharmacologically target this molecule to treat inflammation.
ANIMAL MODEL
Calogero et al. (1999) generated mice harboring deleted Hmg1. Hmg1 -/-
pups were born alive, but died within 24 hours due to hypoglycemia.
Hmg1-deficient mice survived for several days if given glucose
parenterally, then wasted away with pleiotropic defects (but no
alteration in the immune repertoire). Cell lines lacking Hmg1 grew
normally, but the activation of gene expression by the glucocorticoid
receptor (GRL; 138040) was impaired. Thus, Hmg1 is not essential for the
overall organization of chromatin in the cell nucleus, but is critical
for proper transcriptional control by specific transcription factors.
Scaffidi et al. (2002) used embryonic fibroblast cells from Hmgb1 -/-
mice and demonstrated that necrotic cells from these animals have a
greatly reduced ability to promote inflammation, which proves that the
release of an HMGB1 can signal the demise of a cell to its neighbors.
Apoptotic cells do not release HMGB1 even after undergoing secondary
necrosis and partial autolysis, and thus fail to promote inflammation
even if not cleared promptly by phagocytic cells. In apoptotic cells,
HMGB1 is bound firmly to chromatin because of generalized
underacetylation of histone and is released in the extracellular medium
(promoting inflammation) if chromatin deacetylation is prevented. Thus,
cells undergoing apoptosis are programmed to withhold the signal that is
broadcast by cells that have been damaged or killed by trauma.
Despite significant advances in intensive care therapy and antibiotics,
severe sepsis accounts for 9% of all deaths in the United States
annually. Yang et al. (2004) reported that serum HMGB1 levels are
increased significantly in a standardized model of murine sepsis,
beginning at 18 hours after surgical induction of peritonitis. Specific
inhibition of HMGB1 activity (with either an anti-HMGB1 antibody or with
the DNA-binding A box) beginning as late as 24 hours after surgical
induction of peritonitis significantly increased survival. Animals
treated with either HMGB1 antagonist were protected against development
of organ injury, as evidenced by improved levels of serum creatinine and
blood urea nitrogen. These observations demonstrated that specific
inhibition of endogenous HMGB1 therapeutically reverses lethality of
established sepsis, indicating that HMGB1 inhibitors can be administered
in a clinically relevant time frame.
Maroso et al. (2010) showed that chemical induction of seizures in mice
resulted in increased cytoplasmic expression of Hmgb1 in astrocytes in
the hippocampus, as well as increased expression of Tlr4 (603030) in
neurons within the pyramidal cell layers. The seizures most resembled
temporal lobe epilepsy (TLE, see, e.g., ETL1; 600512) in humans. Brain
tissue from patients with TLE showed increased HMGB1 and TLR4 expression
compared to controls. The authors noted that HMGB1 can bind to and
activate TLR4 (Apetoh et al., 2007). In vitro studies showed that
neurons undergoing glutamate-induced cytotoxic cell death released
Hmgb1. In mice, Hmgb1 was found to cause seizures in wildtype mice, but
not in those with inactivation of the Tlr4 gene. Antagonists of Hmgb1
and Tlr4 retarded seizure precipitation and decreased acute and chronic
seizure recurrence. Overall, the findings indicated that HMGB1-TLR4
signaling may contribute to the generation and perpetuation of seizures.
*FIELD* RF
1. Apetoh, L.; Ghiringhelli, F.; Tesniere, A.; Obeid, M.; Ortiz, C.;
Criollo, A.; Mignot, G.; Maiuri, M. C.; Ullrich, E.; Saulnier, P.;
Yang, H.; Amigorena, S.; and 16 others: Toll-like receptor 4-dependent
contribution of the immune system to anticancer chemotherapy and radiotherapy. Nature
Med. 13: 1050-1059, 2007.
2. Bianchi, M. E.; Beltrame, M.; Paonessa, G.: Specific recognition
of cruciform DNA by nuclear protein HMG1. Science 243: 1056-1059,
1989.
3. Calogero, S.; Grassi, F.; Aguzzi, A.; Voigtlander, T.; Ferrier,
P.; Ferrari, S.; Bianchi, M. E.: The lack of chromosomal protein
Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia
in newborn mice. Nature Genet. 22: 276-280, 1999.
4. Ferrari, S.; Finelli, P.; Rocchi, M.; Bianchi, M. E.: The active
gene that encodes human high mobility group 1 protein (HMG1) contains
introns and maps to chromosome 13. Genomics 35: 367-371, 1996.
5. Lotze, M. T.; Tracey, K. J.: High-mobility group box 1 protein
(HMGB1): nuclear weapon in the immune arsenal. Nature Rev. Immun. 5:
331-342, 2005.
6. Lu, B.; Nakamura, T.; Inouye, K.; Li, J.; Tang, Y.; Lundback, P.;
Valdes-Ferrer, S. I.; Olofsson, P. S.; Kalb, T.; Roth, J.; Zou, Y.;
Erlandsson-Harris, H.; Yang, H.; Ting, J. P.-Y.; Wang, H.; Andersson,
U.; Antoine, D. J.; Chavan, S. S.; Hotamisligil, G. S.; Tracey, K.
J.: Novel role of PKR in inflammasome activation and HMGB1 release. Nature 488:
670-674, 2012.
7. Maroso, M.; Balosso, S.; Ravizza, T.; Liu, J.; Aronica, E.; Iyer,
A. M.; Rossetti, C.; Molteni, M.; Casalgrandi, M.; Manfredi, A. A.;
Bianchi, M. E.; Vezzani, A.: Toll-like receptor 4 and high-mobility
group box-1 are involved in ictogenesis and can be targeted to reduce
seizures. Nature Med. 16: 413-419, 2010.
8. Prasad, R.; Liu, Y.; Deterding, L. J.; Poltoratsky, V. P.; Kedar,
P. S.; Horton, J. K.; Kanno, S.-I.; Asagoshi, K.; Hou, E. W.; Khodyreva,
S. N.; Lavrik, O. I.; Tomer, K. B.; Yasui, A.; Wilson, S. H.: HMGB1
is a cofactor in mammalian base excision repair. Molec. Cell 27:
829-841, 2007.
9. Scaffidi, P.; Misteli, T.; Bianchi, M. E.: Release of chromatin
protein HMGB1 by necrotic cells triggers inflammation. Nature 418:
191-195, 2002. Note: Erratum: Nature 467: 622 only, 2010.
10. Taguchi, A.; Blood, D. C.; del Toro, G.; Canet, A.; Lee, D. C.;
Qu, W.; Tanji, N.; Lu, Y.; Lalla, E.; Fu, C.; Hofmann, M. A.; Kislinger,
T.; Ingram, M.; Lu, A.; Tanaka, H.; Hori, O.; Ogawa, S.; Stern, D.
M.; Schmidt, A. M.: Blockade of RAGE-amphoterin signalling suppresses
tumour growth and metastases. Nature 405: 354-360, 2000.
11. Wang, H.; Bloom, O.; Zhang, M.; Vishnubhakat, J. M.; Ombrellino,
M.; Che, J.; Frazier, A.; Yang, H.; Ivanova, S.; Borovikova, L.; Manogue,
K. R.; Faist, E.; Abraham, E.; Andersson, J.; Andersson, U.; Molina,
P. E.; Abumrad, N. N.; Sama, A.; Tracey, K. J.: HMG-1 as a late mediator
of endotoxin lethality in mice. Science 285: 248-251, 1999.
12. Wen, L.; Huang, J.-K.; Johnson, B. H.; Reeck, G. R.: A human
placental cDNA clone that encodes nonhistone chromosomal protein HMG-1. Nucleic
Acids Res. 17: 1197-1214, 1989.
13. Yanai, H.; Ban, T.; Wang, Z.; Choi, M. K.; Kawamura, T.; Negishi,
H.; Nakasato, M.; Lu, Y.; Hangai, S.; Koshiba, R.; Savitsky, D.; Ronfani,
L.; Akira, S.; Bianchi, M. E.; Honda, K.; Tamura, T.; Kodama, T.;
Taniguchi, T.: HMGB proteins function as universal sentinels for
nucleic-acid-mediated innate immune responses. Nature 462: 99-103,
2009.
14. Yang, H.; Ochani, M; Li, J.; Qiang, X.; Tanovic, M.; Harris, H.
E.; Susarla, S. M.; Ulloa, L.; Wang, H.; DiRaimo, R.; Czura, C. J.;
Wang, H.; Roth, J.; Warren, H. S.; Fink, M. P.; Fenton, M. J.; Andersson,
U.; Tracey, K. J.: Reversing established sepsis with antagonists
of endogenous high-mobility group box 1. Proc. Nat. Acad. Sci. 101:
296-301, 2004.
15. Zetterstrom, C. K.; Bergman, T.; Rynnel-Dagoo, B.; Harris, H.
E.; Soder, O.; Andersson, U.; Boman, H. B.: High mobility group box
chromosomal protein 1 (HMGB1) is an antibacterial factor produced
by the human adenoid. Pediat. Res. 52: 148-154, 2002.
*FIELD* CN
Ada Hamosh - updated: 9/18/2012
Cassandra L. Kniffin - updated: 5/27/2010
Paul J. Converse - updated: 11/25/2009
Patricia A. Hartz - updated: 2/7/2008
Paul J. Converse - updated: 4/12/2007
Natalie E. Krasikov - updated: 7/29/2004
Victor A. McKusick - updated: 2/6/2004
Ada Hamosh - updated: 7/22/2002
Ada Hamosh - updated: 5/18/2000
Ada Hamosh - updated: 7/9/1999
Victor A. McKusick - updated: 6/24/1999
*FIELD* CD
Victor A. McKusick: 6/19/1992
*FIELD* ED
alopez: 09/20/2012
terry: 9/18/2012
terry: 9/28/2011
alopez: 10/12/2010
wwang: 6/15/2010
ckniffin: 5/27/2010
mgross: 11/30/2009
terry: 11/25/2009
carol: 6/3/2009
mgross: 2/20/2008
terry: 2/7/2008
carol: 2/5/2008
mgross: 4/13/2007
terry: 4/12/2007
wwang: 12/2/2005
terry: 11/3/2004
carol: 7/29/2004
cwells: 2/11/2004
terry: 2/6/2004
carol: 8/28/2002
alopez: 7/25/2002
terry: 7/22/2002
alopez: 5/18/2000
alopez: 7/9/1999
terry: 7/9/1999
alopez: 6/28/1999
terry: 6/24/1999
alopez: 5/27/1999
alopez: 5/26/1999
terry: 9/6/1996
terry: 8/6/1996
mark: 4/8/1996
mimadm: 4/26/1994
carol: 6/19/1992
*RECORD*
*FIELD* NO
163905
*FIELD* TI
*163905 HIGH MOBILITY GROUP BOX 1; HMGB1
;;HIGH MOBILITY GROUP PROTEIN 1; HMG1;;
CHROMOSOMAL PROTEIN, NONHISTONE, HMG1;;
read moreNONHISTONE CHROMOSOMAL PROTEIN HMG1;;
AMPHOTERIN
*FIELD* TX
CLONING
The HMG (high mobility group) proteins are nonhistone chromosomal
proteins. Wen et al. (1989) isolated a cDNA clone that encodes the
entire 215-amino acid sequence of HMG1 from a human placenta cDNA
library. Northern blot analysis showed that 3 mRNA species of
approximately 1.0, 1.4, and 2.4 kb were expressed in all mammalian
organs and cell lines examined. The HMG1 protein has a molecular mass of
approximately 25 kD.
GENE STRUCTURE
A large number of sequences related to the cDNA for HMG1 protein
hampered the cloning and mapping of the active HMG1 gene. Ferrari et al.
(1996) showed that the HMG1 gene contains introns, whereas the
HMG1-related sequences do not and most likely are retrotransposed
pseudogenes. They identified 8 YACs from the ICI and CEPH libraries that
contain the human HMG1 gene. The gene is similar in structure to the
previously characterized mouse homolog.
MAPPING
Ferrari et al. (1996) mapped the HMG1 gene to chromosome 13q12 by
fluorescence in situ hybridization. The mouse Hmg1 gene maps to the
telomeric region of murine chromosome 5, which has syntenic homology
with human chromosome 13q12.
GENE FUNCTION
High mobility group-1 protein is an abundant component of all mammalian
nuclei, and related proteins exist in all eukaryotes. HMG1 binds with
high affinity to specific DNA structures such as bent or kinked DNA
(Bianchi et al., 1989). It is considered to be a structural protein of
chromatin.
Wang et al. (1999) identified HMG1 as a potential late mediator of
lethality due to endotoxin. HMG1 protein was found to be released by
cultured macrophages more than 8 hours after stimulation with endotoxin,
tumor necrosis factor (TNF; 191160), or interleukin-1 (see 147720). Mice
showed increased serum levels of HMG1 from 8 to 32 hours after endotoxin
exposure. Delayed administration of antibodies to HMG1 attenuated
endotoxin lethality in mice, and administration of HMG1 itself was
lethal. Wang et al. (1999) studied 8 normal subjects and 25 critically
ill septic patients with bacteremia and sepsis-induced organ
dysfunction. HMG1 was not detectable in the serum of normal subjects,
but significant levels were observed in critically ill patients with
sepsis, and these levels were higher in patients who succumbed as
compared to patients with nonlethal infection. The delayed kinetics of
HMG1 release suggested that serum HMG1 levels may be a convenient marker
of disease severity. Moreover, the observations that HMG1 itself is
toxic and that anti-HMG1 prevents lipopolysaccharide lethality, point to
HMG1 as a potential target for therapeutic intervention.
The receptor for advanced glycation end products (RAGE; 600214) is a
central cell surface receptor for HMG1 (amphoterin), a polypeptide
linked to outgrowth of cultured cortical neurons derived from developing
brain. Indeed, the colocalization of RAGE and amphoterin at the leading
edge of advancing neurites indicated their potential contribution to
cellular migration, and in pathologies such as tumor invasion. Taguchi
et al. (2000) demonstrated that blockade of RAGE-amphoterin decreased
growth and metastases of both implanted tumors and tumors developing
spontaneously in susceptible mice. Inhibition of the RAGE-amphoterin
interaction suppressed activation of p44 (601795)/p42 (603441), p38
(600289), and SAP/JNK (601158) MAP kinases, molecular effector
mechanisms linked to tumor proliferation, invasion, and expression of
matrix metalloproteinases.
Zetterstrom et al. (2002) identified HMGB1 as an antibacterial factor
produced and stored intracellularly in the human adenoid gland.
Lotze and Tracey (2005) reviewed the role of HMGB1 as a cytokine
mediating local and systemic responses to necrotic cell death and
cancer, invasion by pathogens, trauma, and sepsis.
Prasad et al. (2007) found that Hmgb1 interacted with stabilized base
excision repair (BER) intermediates in mouse embryonic fibroblasts.
Fluorescence-tagged human HMGB1 accumulated at sites of DNA damage in
HeLa cells, and it stimulated incision activities of APE (APEX; 107748)
and FEN1 (600393) on BER substrates. Coimmunoprecipitation experiments
showed that HMGB1 interacted with BER enzymes. Hmgb1-null mouse
embryonic fibroblasts were less sensitive than wildtype cells to a
methylating agent, probably due to production of fewer strand-break BER
intermediates. Prasad et al. (2007) concluded that HMGB1 is a BER
cofactor that modulates BER capacity.
Using pull-down assays, Yanai et al. (2009) found that mouse HMGB
proteins bound to all immunogenic nucleic acids, with a correlation
between affinity and immunogenicity. Hmgb1 -/- and Hmgb2 (163906) -/-
mouse cells were defective in type I interferon and inflammatory
cytokine induction by DNA or RNA targeted to activate cytosolic nucleic
acid-sensing receptors. Mouse cells in which expression of Hmgb1, Hmgb2,
and Hmgb3 (300193) was suppressed by small interfering RNA also had
impaired activation of transcription factors Irf3 (603734) and Nfkb (see
164011). The lack of HMGBs also resulted in poorer activation of
Toll-like receptor-3 (Tlr3; 603029), Tlr7 (300365), and Tlr9 (605474) by
their cognate nucleic acids (dsRNA, ssRNA, and hypomethylated DNA,
respectively). Yanai et al. (2009) concluded that selective activation
of nucleic acid-sensing receptors is contingent on the more promiscuous
sensing of nucleic acids by HMGBs and may have implications for the
treatment of immunologic disorders.
By studying HMGB1 release mechanisms, Lu et al. (2012) identified a role
for PKR (176871) in inflammasome activation. Exposure of macrophages to
inflammasome agonists induced PKR autophosphorylation. PKR inactivation
by genetic deletion or pharmacologic inhibition severely impaired
inflammasome activation in response to double-stranded RNA, ATP,
monosodium urate, adjuvant aluminum, rotenone, live E. coli, anthrax
lethal toxin, DNA transfection, and S. typhimurium infection. PKR
deficiency significantly inhibited the secretion of IL1-beta (147720),
IL18 (600953), and HMGB1 in E. coli-induced peritonitis. PKR physically
interacts with several inflammasome components, including NLRP3
(606416), NLRP1 (606636), NLRC4 (606831), and AIM2 (604578), and broadly
regulates inflammasome activation. PKR autophosphorylation in a
cell-free system with recombinant NLRP3, ASC (PYCARD; 606838), and
pro-caspase-1 (147678) reconstituted inflammasome activity. Lu et al.
(2012) concluded that their results showed a crucial role for PKR in
inflammasome activation, and indicated that it should be possible to
pharmacologically target this molecule to treat inflammation.
ANIMAL MODEL
Calogero et al. (1999) generated mice harboring deleted Hmg1. Hmg1 -/-
pups were born alive, but died within 24 hours due to hypoglycemia.
Hmg1-deficient mice survived for several days if given glucose
parenterally, then wasted away with pleiotropic defects (but no
alteration in the immune repertoire). Cell lines lacking Hmg1 grew
normally, but the activation of gene expression by the glucocorticoid
receptor (GRL; 138040) was impaired. Thus, Hmg1 is not essential for the
overall organization of chromatin in the cell nucleus, but is critical
for proper transcriptional control by specific transcription factors.
Scaffidi et al. (2002) used embryonic fibroblast cells from Hmgb1 -/-
mice and demonstrated that necrotic cells from these animals have a
greatly reduced ability to promote inflammation, which proves that the
release of an HMGB1 can signal the demise of a cell to its neighbors.
Apoptotic cells do not release HMGB1 even after undergoing secondary
necrosis and partial autolysis, and thus fail to promote inflammation
even if not cleared promptly by phagocytic cells. In apoptotic cells,
HMGB1 is bound firmly to chromatin because of generalized
underacetylation of histone and is released in the extracellular medium
(promoting inflammation) if chromatin deacetylation is prevented. Thus,
cells undergoing apoptosis are programmed to withhold the signal that is
broadcast by cells that have been damaged or killed by trauma.
Despite significant advances in intensive care therapy and antibiotics,
severe sepsis accounts for 9% of all deaths in the United States
annually. Yang et al. (2004) reported that serum HMGB1 levels are
increased significantly in a standardized model of murine sepsis,
beginning at 18 hours after surgical induction of peritonitis. Specific
inhibition of HMGB1 activity (with either an anti-HMGB1 antibody or with
the DNA-binding A box) beginning as late as 24 hours after surgical
induction of peritonitis significantly increased survival. Animals
treated with either HMGB1 antagonist were protected against development
of organ injury, as evidenced by improved levels of serum creatinine and
blood urea nitrogen. These observations demonstrated that specific
inhibition of endogenous HMGB1 therapeutically reverses lethality of
established sepsis, indicating that HMGB1 inhibitors can be administered
in a clinically relevant time frame.
Maroso et al. (2010) showed that chemical induction of seizures in mice
resulted in increased cytoplasmic expression of Hmgb1 in astrocytes in
the hippocampus, as well as increased expression of Tlr4 (603030) in
neurons within the pyramidal cell layers. The seizures most resembled
temporal lobe epilepsy (TLE, see, e.g., ETL1; 600512) in humans. Brain
tissue from patients with TLE showed increased HMGB1 and TLR4 expression
compared to controls. The authors noted that HMGB1 can bind to and
activate TLR4 (Apetoh et al., 2007). In vitro studies showed that
neurons undergoing glutamate-induced cytotoxic cell death released
Hmgb1. In mice, Hmgb1 was found to cause seizures in wildtype mice, but
not in those with inactivation of the Tlr4 gene. Antagonists of Hmgb1
and Tlr4 retarded seizure precipitation and decreased acute and chronic
seizure recurrence. Overall, the findings indicated that HMGB1-TLR4
signaling may contribute to the generation and perpetuation of seizures.
*FIELD* RF
1. Apetoh, L.; Ghiringhelli, F.; Tesniere, A.; Obeid, M.; Ortiz, C.;
Criollo, A.; Mignot, G.; Maiuri, M. C.; Ullrich, E.; Saulnier, P.;
Yang, H.; Amigorena, S.; and 16 others: Toll-like receptor 4-dependent
contribution of the immune system to anticancer chemotherapy and radiotherapy. Nature
Med. 13: 1050-1059, 2007.
2. Bianchi, M. E.; Beltrame, M.; Paonessa, G.: Specific recognition
of cruciform DNA by nuclear protein HMG1. Science 243: 1056-1059,
1989.
3. Calogero, S.; Grassi, F.; Aguzzi, A.; Voigtlander, T.; Ferrier,
P.; Ferrari, S.; Bianchi, M. E.: The lack of chromosomal protein
Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia
in newborn mice. Nature Genet. 22: 276-280, 1999.
4. Ferrari, S.; Finelli, P.; Rocchi, M.; Bianchi, M. E.: The active
gene that encodes human high mobility group 1 protein (HMG1) contains
introns and maps to chromosome 13. Genomics 35: 367-371, 1996.
5. Lotze, M. T.; Tracey, K. J.: High-mobility group box 1 protein
(HMGB1): nuclear weapon in the immune arsenal. Nature Rev. Immun. 5:
331-342, 2005.
6. Lu, B.; Nakamura, T.; Inouye, K.; Li, J.; Tang, Y.; Lundback, P.;
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*FIELD* CN
Ada Hamosh - updated: 9/18/2012
Cassandra L. Kniffin - updated: 5/27/2010
Paul J. Converse - updated: 11/25/2009
Patricia A. Hartz - updated: 2/7/2008
Paul J. Converse - updated: 4/12/2007
Natalie E. Krasikov - updated: 7/29/2004
Victor A. McKusick - updated: 2/6/2004
Ada Hamosh - updated: 7/22/2002
Ada Hamosh - updated: 5/18/2000
Ada Hamosh - updated: 7/9/1999
Victor A. McKusick - updated: 6/24/1999
*FIELD* CD
Victor A. McKusick: 6/19/1992
*FIELD* ED
alopez: 09/20/2012
terry: 9/18/2012
terry: 9/28/2011
alopez: 10/12/2010
wwang: 6/15/2010
ckniffin: 5/27/2010
mgross: 11/30/2009
terry: 11/25/2009
carol: 6/3/2009
mgross: 2/20/2008
terry: 2/7/2008
carol: 2/5/2008
mgross: 4/13/2007
terry: 4/12/2007
wwang: 12/2/2005
terry: 11/3/2004
carol: 7/29/2004
cwells: 2/11/2004
terry: 2/6/2004
carol: 8/28/2002
alopez: 7/25/2002
terry: 7/22/2002
alopez: 5/18/2000
alopez: 7/9/1999
terry: 7/9/1999
alopez: 6/28/1999
terry: 6/24/1999
alopez: 5/27/1999
alopez: 5/26/1999
terry: 9/6/1996
terry: 8/6/1996
mark: 4/8/1996
mimadm: 4/26/1994
carol: 6/19/1992