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high mobility group protein B1; high mobility group protein 1; HMG-1; amphoterin (HMGB1, HMG1)

Function: - mediates neurite outgrowth when present extracellularly - ligand for RAGE - binding to RAGE effects immune function of dendritic cells [3,4] - may function as proinflammatory cytokine [9,10,11,12] - as nuclear protein, binds preferentially single-stranded DNA & unwinds double stranded DNA Structure: - belongs to the HMGB family - contains 2 HMG box DNA-binding domains Compartment: nucleus Expression: - strongly expressed in developing neurons Pathology: - binding to RAGE may inhibit microglial Abeta clearance & enhance Abeta neurotoxicity [7]

Interactions

molecular events

General

DNA-binding protein high-mobility group [HMG] protein nonhistone chromosomal protein

Properties

SIZE: entity length = 215 aa MW = 25 kD COMPARTMENT: cell nucleus MOTIF: HMG box SITE: 9-79 MOTIF: Ser phosphorylation site {S35} HMG box SITE: 95-163 MOTIF: Ser phosphorylation site {S100} acidic region {186-215} MOTIF: acidic residue (SEVERAL)

Database Correlations

OMIM 163905 UniProt P09429 Pfam PF00505 Entrez Gene 3146 Kegg hsa:3146

References

  1. Bergeron S, Madathiparambil T, Swanson PC. Both HMG-boxes and the acidic tail of HMGB1 regulate RAG- mediated recombination signal synapsis and cleavage in vitro. J Biol Chem. 2005 Jul 1; [Epub ahead of print] PMID: 15994314
  2. Dumitriu IE, Baruah P, Manfredi AA, Bianchi ME, Rovere-Querini P. HMGB1: guiding immunity from within. Trends Immunol. 2005 Jul;26(7):381-7. PMID: 15978523
  3. Dumitriu IE, Baruah P, Valentinis B, Voll RE, Herrmann M, Nawroth PP, Arnold B, Bianchi ME, Manfredi AA, Rovere-Querini P. Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J Immunol. 2005 Jun 15;174(12):7506-15. PMID: 15944249
  4. Dumitriu IE, Baruah P, Bianchi ME, Manfredi AA, Rovere-Querini P. Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells. Eur J Immunol. 2005 Jul;35(7):2184-90. PMID: 15915542
  5. Najima Y, Yahagi N, Takeuchi Y, Matsuzaka T, Sekiya M, Nakagawa Y, Amemiya-Kudo M, Okazaki H, Okazaki S, Tamura Y, Iizuka Y, Ohashi K, Harada K, Gotoda T, Nagai R, Kadowaki T, Ishibashi S, Yamada N, Osuga JI, Shimano H. High mobility group protein-B1 (HMGB1) interacts with sterol regulatory element-binding proteins (SREBPs) to enhance their DNA binding. J Biol Chem. 2005 May 12; [Epub ahead of print] PMID: 15894544
  6. Najima Y, Yahagi N, Takeuchi Y, Matsuzaka T, Sekiya M, Nakagawa Y, Amemiya-Kudo M, Okazaki H, Okazaki S, Tamura Y, Iizuka Y, Ohashi K, Harada K, Gotoda T, Nagai R, Kadowaki T, Ishibashi S, Yamada N, Osuga JI, Shimano H. High mobility group protein-B1 (HMGB1) interacts with sterol regulatory element-binding proteins (SREBPs) to enhance their DNA binding. J Biol Chem. 2005 May 12; [Epub ahead of print] PMID: 15894544
  7. Takata K, Kitamura Y, Tsuchiya D, Kawasaki T, Taniguchi T, Shimohama S. High mobility group box protein-1 inhibits microglial Abeta clearance and enhances Abeta neurotoxicity. J Neurosci Res. 2004 Dec 15;78(6):880-91. PMID: 15499593
  8. Palumbo R, Bianchi ME. High mobility group box 1 protein, a cue for stem cell recruitment. Biochem Pharmacol. 2004 Sep 15;68(6):1165-70. Review. PMID: 15313414
  9. Rovere-Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon M, Dumitriu IE, Muller S, Iannacone M, Traversari C, Bianchi ME, Manfredi AA. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep. 2004 Aug;5(8):825-30. Epub 2004 Jul 23. PMID: 15272298
  10. Andersson U, Tracey KJ. HMGB1 as a mediator of necrosis-induced inflammation and a therapeutic target in arthritis. Rheum Dis Clin North Am. 2004 Aug;30(3):627-37, xi. Review. PMID: 15261345
  11. Chen G, Ward MF, Sama AE, Wang H. Extracellular HMGB1 as a proinflammatory cytokine. J Interferon Cytokine Res. 2004 Jun;24(6):329-33. Review. PMID: 15212706
  12. Erlandsson Harris H, Andersson U. Mini-review: The nuclear protein HMGB1 as a proinflammatory mediator. Eur J Immunol. 2004 Jun;34(6):1503-12. Review. PMID: 15162419
  13. UniProt :accession P09429
  14. SeattleSNPs http://pga.gs.washington.edu/data/hmgb1/