hmgb2 protein


Summary: A 23-kDa HMG-box protein that binds to and distorts the minor grove of DNA.

Top Publications

  1. Zimmerman J, Maher L. Transient HMGB protein interactions with B-DNA duplexes and complexes. Biochem Biophys Res Commun. 2008;371:79-84 pubmed publisher
    ..We also detect novel complexes in which HMGB proteins simultaneously bind more than one DNA duplex. ..
  2. Zhang J, McCauley M, Maher L, Williams M, Israeloff N. Basic N-terminus of yeast Nhp6A regulates the mechanism of its DNA flexibility enhancement. J Mol Biol. 2012;416:10-20 pubmed publisher
    ..Therefore, the basic N-terminus of Nhp6A is responsible for its ability to act as a flexible hinge and to form high-order structures. ..
  3. Zhang J, McCauley M, Maher L, Williams M, Israeloff N. Mechanism of DNA flexibility enhancement by HMGB proteins. Nucleic Acids Res. 2009;37:1107-14 pubmed publisher
    ..Therefore, the mechanism by which HMGB proteins enhance the flexibility of DNA must differ from that of the Escherichia coli HU protein, which in previous studies showed a flat angle distribution consistent with a flexible hinge model. ..
  4. McCauley M, Hardwidge P, Maher L, Williams M. Dual binding modes for an HMG domain from human HMGB2 on DNA. Biophys J. 2005;89:353-64 pubmed
    ..However, at higher protein concentrations, a cooperative filament mode is observed instead of the hinge binding. This mode may be uniquely characterized by this high-force optical tweezers experiment. ..
  5. McCauley M, Zimmerman J, Maher L, Williams M. HMGB binding to DNA: single and double box motifs. J Mol Biol. 2007;374:993-1004 pubmed
    ..In addition, at low concentrations, the single box protein can alter DNA flexibility without stabilizing dsDNA, whereas stabilization at higher concentrations is likely achieved through a cooperative binding mode. ..
  6. Sebastian N, Bystry E, Becker N, Maher L. Enhancement of DNA flexibility in vitro and in vivo by HMGB box A proteins carrying box B residues. Biochemistry. 2009;48:2125-34 pubmed publisher
    ..These results demonstrate important roles for cationic leader amino acids in HMGB folding, DNA interaction, and DNA bending. ..
  7. Stros M, Ozaki T, Bacikova A, Kageyama H, Nakagawara A. HMGB1 and HMGB2 cell-specifically down-regulate the p53- and p73-dependent sequence-specific transactivation from the human Bax gene promoter. J Biol Chem. 2002;277:7157-64 pubmed
    ..A possible mechanism of HMGB1-mediated modulation of p73- and p53-dependent transactivation is discussed. ..
  8. Wong T, Rajagopalan S, Freund S, Rutherford T, Andreeva A, Townsley F, et al. Biophysical characterizations of human mitochondrial transcription factor A and its binding to tumor suppressor p53. Nucleic Acids Res. 2009;37:6765-83 pubmed publisher
    ..In addition, the DNA-binding mechanism of TFAM and biological relevance of the TFAM-p53 interaction are discussed. ..
  9. Federovitch C, Jones Y, Tong A, Boone C, Prinz W, Hampton R. Genetic and structural analysis of Hmg2p-induced endoplasmic reticulum remodeling in Saccharomyces cerevisiae. Mol Biol Cell. 2008;19:4506-20 pubmed publisher
    ..These phospholipid effects, unlike Hmg2p-induced ER remodeling, required the enzymatic activity of Hmg2p. Together, our results indicate that, although related, Hmg2p- and Hmg1p-induced ER remodeling are mechanistically distinct. ..

More Information


  1. Fan Z, Beresford P, Zhang D, Lieberman J. HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A. Mol Cell Biol. 2002;22:2810-20 pubmed
  2. Kwon J, Kim J, Park J, Hong S, Park C, Hong S, et al. Overexpression of high-mobility group box 2 is associated with tumor aggressiveness and prognosis of hepatocellular carcinoma. Clin Cancer Res. 2010;16:5511-21 pubmed publisher
    ..HMGB2 mRNA levels were measured in 334 HCC patients by real-time reverse transcription-PCR and HMGB2 protein levels in 173 HCC patients by immunohistochemical studies...
  3. Janke C, Martin D, Giraud Panis M, Decoville M, Locker D. Drosophila DSP1 and rat HMGB1 have equivalent DNA binding properties and share a similar secondary fold. J Biochem. 2003;133:533-9 pubmed
    ..The major structural difference between the two proteins, the glutamine-rich N-terminal tail of DSP1, which does not exist in HMGB1, did not interfere with any of the studied DNA-binding properties of the proteins. ..
  4. Zhang C, Chang P, Lippard S. Identification of nuclear proteins that interact with platinum-modified DNA by photoaffinity labeling. J Am Chem Soc. 2004;126:6536-7 pubmed
    ..Several DNA-protein cross-linked adducts were identified that may function in the cellular processing of cisplatin-DNA adducts. Of these, PARP-1 had not previously been demonstrated directly to contact Pt-DNA cross-links in human cells. ..
  5. Gissot M, Ting L, Daly T, Bergman L, Sinnis P, Kim K. High mobility group protein HMGB2 is a critical regulator of plasmodium oocyst development. J Biol Chem. 2008;283:17030-8 pubmed publisher
    ..Therefore, sexual stage protein expression appears to be both transcriptionally and translationally regulated with Plasmodium HMGB2 acting as an important regulator of malaria sexual stage gene expression. ..
  6. Balani P, Boulaire J, Zhao Y, Zeng J, Lin J, Wang S. High mobility group box2 promoter-controlled suicide gene expression enables targeted glioblastoma treatment. Mol Ther. 2009;17:1003-11 pubmed publisher
    ..Our results suggest that the novel 5' sequence of HMGB2 gene has a potential to be used as an efficient, tumor-selective promoter in targeted vectors for glioblastoma gene therapy. ..
  7. Lucas E, Dyer N, Murakami K, Lee Y, Chan Y, Grimaldi G, et al. Loss of Endometrial Plasticity in Recurrent Pregnancy Loss. Stem Cells. 2016;34:346-56 pubmed publisher
    ..Our findings indicate that stem cell deficiency and accelerated stromal senescence limit the differentiation capacity of the endometrium and predispose for pregnancy failure. ..
  8. Takeda T, Izumi H, Kitada S, Uramoto H, Tasaki T, Zhi L, et al. The combination of a nuclear HMGB1-positive and HMGB2-negative expression is potentially associated with a shortened survival in patients with pancreatic ductal adenocarcinoma. Tumour Biol. 2014;35:10555-69 pubmed publisher
    ..Therefore, the combination of a HMGB1+ and HMGB2- expression potentially predicts a poor prognosis in patients with PDAC, and these new biomarkers may be useful parameters for clinical management in the early postoperative phase. ..
  9. Potash J, Buervenich S, Cox N, Zandi P, Akula N, Steele J, et al. Gene-based SNP mapping of a psychotic bipolar affective disorder linkage region on 22q12.3: association with HMG2L1 and TOM1. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:59-67 pubmed
    ..Further work is needed to confirm these results and uncover the functional variation underlying the association signal. ..
  10. Nakamura Y, Shimizu M, Yoshida M. Distorted DNA structures induced by HMGB2 possess a high affinity for HMGB2. J Biochem. 2002;131:153-60 pubmed
    ..Thus, the distorted structures present in alpha-DNA and beta-DNA should be important in considering the functional mechanisms in which HMGB2 participates. ..
  11. Ciubotaru M, Schatz D. Synapsis of recombination signal sequences located in cis and DNA underwinding in V(D)J recombination. Mol Cell Biol. 2004;24:8727-44 pubmed
    ..We propose that this unwinding is uniquely sensed during synapsis of an appropriate 12/23 pair of RSSs. ..
  12. Yanai H, Ban T, Wang Z, Choi M, Kawamura T, Negishi H, et al. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature. 2009;462:99-103 pubmed publisher
    ..These findings may have implications for understanding the evolution of the innate immune system and for the treatment of immunological disorders. ..
  13. Taniguchi N, Caramés B, Hsu E, Cherqui S, Kawakami Y, Lotz M. Expression patterns and function of chromatin protein HMGB2 during mesenchymal stem cell differentiation. J Biol Chem. 2011;286:41489-98 pubmed publisher
    ..The age-related loss of HMGB2 in articular cartilage may represent a mechanism responsible for the decline in adult cartilage stem cell populations. ..
  14. Walisko O, Schorn A, Rolfs F, Devaraj A, Miskey C, Izsvák Z, et al. Transcriptional activities of the Sleeping Beauty transposon and shielding its genetic cargo with insulators. Mol Ther. 2008;16:359-69 pubmed
  15. Lee M, Roy M, Ong S, Mertins P, Villani A, Li W, et al. Identification of regulators of the innate immune response to cytosolic DNA and retroviral infection by an integrative approach. Nat Immunol. 2013;14:179-85 pubmed publisher
  16. Guermah M, Palhan V, Tackett A, Chait B, Roeder R. Synergistic functions of SII and p300 in productive activator-dependent transcription of chromatin templates. Cell. 2006;125:275-86 pubmed
    ..The purification of CTEA also identified HMGB2 as a coactivator that, while inactive on its own, enhances SII and p300 functions. ..
  17. Stros M, Polanská E, Struncová S, Pospisilova S. HMGB1 and HMGB2 proteins up-regulate cellular expression of human topoisomerase IIalpha. Nucleic Acids Res. 2009;37:2070-86 pubmed publisher
  18. Swanson P. The bounty of RAGs: recombination signal complexes and reaction outcomes. Immunol Rev. 2004;200:90-114 pubmed
    ..Finally, I discuss alternative DNA transactions mediated by the V(D)J recombinase, the protein-DNA complexes that support them, and factors and forces that control them. ..
  19. Laurent B, Randrianarison Huetz V, Marechal V, Marchal V, Mayeux P, Dusanter Fourt I, et al. High-mobility group protein HMGB2 regulates human erythroid differentiation through trans-activation of GFI1B transcription. Blood. 2010;115:687-95 pubmed publisher
    ..We propose that HMGB2 potentiates GATA-1-dependent transcription of GFI1B by Oct-1 and thereby controls erythroid differentiation. ..
  20. Manrique Carpintero N, Tokuhisa J, Ginzberg I, Holliday J, Veilleux R. Sequence diversity in coding regions of candidate genes in the glycoalkaloid biosynthetic pathway of wild potato species. G3 (Bethesda). 2013;3:1467-79 pubmed publisher
    ..These results can be used to evaluate SGA accumulation in segregating or association mapping populations. ..
  21. Shin Y, Kim M, Kim M, Lee J, Kang M, Jeong J. High-mobility group box 2 (HMGB2) modulates radioresponse and is downregulated by p53 in colorectal cancer cell. Cancer Biol Ther. 2013;14:213-21 pubmed publisher
    ..Our study revealed that HMGB2 is necessary to protect colorectal cancer cells from DNA damage and efficient DNA repair and p53-mediated downregulation is a critical mechanism of modulating HMGB2 expression. ..
  22. Ueda T, Shirakawa H, Yoshida M. Involvement of HMGB1 and HMGB2 proteins in exogenous DNA integration reaction into the genome of HeLa S3 cells. Biochim Biophys Acta. 2002;1593:77-84 pubmed
  23. Stefanovsky V, Langlois F, Bazett Jones D, Pelletier G, Moss T. ERK modulates DNA bending and enhancesome structure by phosphorylating HMG1-boxes 1 and 2 of the RNA polymerase I transcription factor UBF. Biochemistry. 2006;45:3626-34 pubmed
    ..The data demonstrate that ERK phosphorylation of UBF prevents DNA bending by its first two HMG boxes, leading to a cooperative unfolding of the enhancesome. ..
  24. Metukuri M, Reddy C, Reddy P, Reddanna P. Bacterial LPS-mediated acute inflammation-induced spermatogenic failure in rats: role of stress response proteins and mitochondrial dysfunction. Inflammation. 2010;33:235-43 pubmed publisher
    ..In conclusion, the present study shows the involvement of stress response proteins and mitochondrial dysfunction in LPS-induced germ cell death in male rats...
  25. Chakravarti D, Hong R. SET-ting the stage for life and death. Cell. 2003;112:589-91 pubmed
    ..Work from the Lieberman and Wang groups indicates a surprising role for a group of acidic nucleo-cytoplasmic proteins in regulating apoptosis. ..
  26. Ugrinova I, Pashev I, Pasheva E. Nucleosome binding properties and Co-remodeling activities of native and in vivo acetylated HMGB-1 and HMGB-2 proteins. Biochemistry. 2009;48:6502-7 pubmed publisher
    ..Acetylation of HMGB-1 and -2 proteins enhanced binding of SWI/SNF to the nucleosome but did not affect its ATPase activity. ..
  27. Varma R, Hector S, Clark K, Greco W, Hawthorn L, Pendyala L. Gene expression profiling of a clonal isolate of oxaliplatin-resistant ovarian carcinoma cell line A2780/C10. Oncol Rep. 2005;14:925-32 pubmed
    ..The identification of these genes should aid in a better understanding of the pathways resulting in platinum drug resistance. ..
  28. Dissanayake S. Immunomodulation by parasites: high mobility group 2 (HMG-2) protein is a putative intracellular mediator for fucosylated sugars of Schistosoma mansoni. Mol Immunol. 2002;38:911-9 pubmed
    ..These data suggest that HMG-2 protein may function as a putative intracellular receptor/mediator for fucosylated sugars of parasites. ..
  29. Franklin S, Chen H, Mitchell Jordan S, Ren S, Wang Y, Vondriska T. Quantitative analysis of the chromatin proteome in disease reveals remodeling principles and identifies high mobility group protein B2 as a regulator of hypertrophic growth. Mol Cell Proteomics. 2012;11:M111.014258 pubmed publisher
  30. Ignea C, Trikka F, Kourtzelis I, Argiriou A, Kanellis A, Kampranis S, et al. Positive genetic interactors of HMG2 identify a new set of genetic perturbations for improving sesquiterpene production in Saccharomyces cerevisiae. Microb Cell Fact. 2012;11:162 pubmed publisher
    ..The approach presented here allows new genetic perturbations to be compiled on yeast cell factory strains without negatively impacting cell growth and viability. ..
  31. Mansilla Soto J, Cortes P. VDJ recombination: Artemis and its in vivo role in hairpin opening. J Exp Med. 2003;197:543-7 pubmed
  32. Chen Y, Chen W, Cobb M, Zhao Y. PTMap--a sequence alignment software for unrestricted, accurate, and full-spectrum identification of post-translational modification sites. Proc Natl Acad Sci U S A. 2009;106:761-6 pubmed publisher
    ..Our results demonstrate that PTMap is a powerful algorithm capable of identification of all possible protein PTMs with high confidence. ..
  33. Stemmer C, Leeming D, Franssen L, Grimm R, Grasser K. Phosphorylation of maize and Arabidopsis HMGB proteins by protein kinase CK2alpha. Biochemistry. 2003;42:3503-8 pubmed
  34. Yamada S, Maruyama I. HMGB1, a novel inflammatory cytokine. Clin Chim Acta. 2007;375:36-42 pubmed
    ..In this report, we review the physiological and pathological significance of HMGB1 and describe the development of an assay method for this pleiotropic protein. ..
  35. Lv X, Xu D, Liu D, Li L, Hao D, Liang C. High-mobility group protein 2 may be involved in the locus control region regulation of the beta-globin gene cluster. Biochem Cell Biol. 2002;80:765-70 pubmed
    ..This indicates that the AT-rich region in human hypersensitive site 2 may take part in the regulation of the beta-globin gene cluster by facilitating DNA bending, which is a prerequisite for the looping mechanism in this region. ..
  36. Hamamouch N, Westwood J, Banner I, Cramer C, Gepstein S, Aly R. A peptide from insects protects transgenic tobacco from a parasitic weed. Transgenic Res. 2005;14:227-36 pubmed
    ..The transgenic plants were similar in appearance to non-transformed plants suggesting that sarcotoxin IA is not detrimental to the host...
  37. Rabinovich E, Kerem A, Frohlich K, Diamant N, Bar Nun S. AAA-ATPase p97/Cdc48p, a cytosolic chaperone required for endoplasmic reticulum-associated protein degradation. Mol Cell Biol. 2002;22:626-34 pubmed
  38. Julian M, Shao G, Vangundy Z, Papenfuss T, Crouser E. Mitochondrial transcription factor A, an endogenous danger signal, promotes TNF? release via RAGE- and TLR9-responsive plasmacytoid dendritic cells. PLoS ONE. 2013;8:e72354 pubmed publisher
    ..These findings, and others reported herein, significantly advance our understanding of sterile immune responses triggered by mitochondrial danger signals. ..
  39. Küchler R, Schroeder B, Jaeger S, Stange E, Wehkamp J. Antimicrobial activity of high-mobility-group box 2: a new function to a well-known protein. Antimicrob Agents Chemother. 2013;57:4782-93 pubmed publisher
    ..Taken together, we characterized HMGB2 as an antimicrobial protein in intestinal tissue, complementing the diverse repertoire of gut mucosal defense molecules. ..
  40. Qi M, Tagawa K, Enokido Y, Yoshimura N, Wada Y, Watase K, et al. Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases. Nat Cell Biol. 2007;9:402-14 pubmed
    ..Furthermore, HMGBs repressed genotoxic stress signals induced by mutant Htt or transcriptional repression. Thus, HMGBs may be critical regulators of polyQ disease pathology and could be targets for therapy development. ..
  41. Ohyama K, Suzuki M, Masuda K, Yoshida S, Muranaka T. Chemical phenotypes of the hmg1 and hmg2 mutants of Arabidopsis demonstrate the in-planta role of HMG-CoA reductase in triterpene biosynthesis. Chem Pharm Bull (Tokyo). 2007;55:1518-21 pubmed
    ..These results demonstrate that HMGR2 as well as HMGR1 is responsible for the biosynthesis of triterpenes in spite of the lack of visible phenotypes in hmg2. ..
  42. Kalinowska Herok M, Widłak P. High mobility group proteins stimulate DNA cleavage by apoptotic endonuclease DFF40/CAD due to HMG-box interactions with DNA. Acta Biochim Pol. 2008;55:21-6 pubmed
    ..The data presented suggest that changes induced in DNA conformation upon HMG-box binding makes the substrate more accessible to cleavage by DFF40/CAD nuclease and thus may contribute to preferential linker DNA cleavage during apoptosis. ..
  43. Kumar K, Singal A, Rizvi M, Chauhan V. High mobility group box (HMGB) proteins of Plasmodium falciparum: DNA binding proteins with pro-inflammatory activity. Parasitol Int. 2008;57:150-7 pubmed publisher
    ..These results suggest that secreted PfHMGB1 and PfHMGB2 may be responsible for eliciting/ triggering host inflammatory immune responses associated with malaria infection. ..
  44. Jourdan N, Jobart Malfait A, Dos Reis G, Quignon F, Piolot T, Klein C, et al. Live-cell imaging reveals multiple interactions between Epstein-Barr virus nuclear antigen 1 and cellular chromatin during interphase and mitosis. J Virol. 2012;86:5314-29 pubmed publisher
    ..Although the depletion of HMGB2 partly altered EBNA-1 association with chromatin in HeLa cells during interphase and mitosis, it did not significantly impact the maintenance of EBV episomes in Raji cells. ..
  45. Koon N, Schneider Stock R, Sarlomo Rikala M, Lasota J, Smolkin M, Petroni G, et al. Molecular targets for tumour progression in gastrointestinal stromal tumours. Gut. 2004;53:235-40 pubmed
    ..These results provide insight into the oncogenesis of GISTs and suggest that testing the expression profile of a number of genes may segregate GISTs into groups of different tumour behaviour. ..
  46. Veilleux S, Boissonneault G. Dynamics of reporter gene stimulation by HMG box proteins. DNA Cell Biol. 2002;21:199-212 pubmed
  47. Takeuchi T, Sakazume K, Tonooka A, Zaitsu M, Takeshima Y, Mikami K, et al. Cytosolic HMGB1 expression in human renal clear cell cancer indicates higher pathological T classifications and tumor grades. Urol J. 2013;10:960-5 pubmed
    ..HMGB1 expressed in the cytoplasm may be an effective marker indicating higher T classifications and tumor grades. ..
  48. Krynetskaia N, Phadke M, Jadhav S, Krynetskiy E. Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage. Mol Cancer Ther. 2009;8:864-72 pubmed publisher
    ..These findings identify new molecular components of the DNA damage signaling cascade and provide novel promising targets for chemotherapeutic intervention. ..
  49. Polanská E, Dobsáková Z, Dvorácková M, Fajkus J, Stros M. HMGB1 gene knockout in mouse embryonic fibroblasts results in reduced telomerase activity and telomere dysfunction. Chromosoma. 2012;121:419-31 pubmed publisher
    ..The ability of HMGB1 to modulate cellular activity of telomerase and to maintain telomere integrity can help to understand some aspects of the protein involvement in chromosome stability and cancer. ..
  50. Das D, Peterson R, Scovell W. High mobility group B proteins facilitate strong estrogen receptor binding to classical and half-site estrogen response elements and relax binding selectivity. Mol Endocrinol. 2004;18:2616-32 pubmed
    ..Models for these interactions are discussed, together with a hit-and-run mechanism that HMGB proteins may utilize to produce these effects. ..
  51. Zhou J, Hu G, Wang X. Repression of smooth muscle differentiation by a novel high mobility group box-containing protein, HMG2L1. J Biol Chem. 2010;285:23177-85 pubmed publisher
    ..This study provides the first evidence of this novel HMG2L1 molecule playing an important role in attenuating smooth muscle differentiation. ..
  52. Wysocka Kapcinska M, Lutyk Nadolska J, Kiliszek M, Plochocka D, Maciag M, Leszczynska A, et al. Functional expression of human HMG-CoA reductase in Saccharomyces cerevisiae: a system to analyse normal and mutated versions of the enzyme in the context of statin treatment. J Appl Microbiol. 2009;106:895-902 pubmed publisher
    ..Our results suggest that this model system is suitable for the development and selection of lipid-lowering drugs as well as for the examination of DNA sequence variations in the context of statin therapy. ..
  53. Pusterla T, De Marchis F, Palumbo R, Bianchi M. High mobility group B2 is secreted by myeloid cells and has mitogenic and chemoattractant activities similar to high mobility group B1. Autoimmunity. 2009;42:308-10 pubmed
    ..Since extracellular HMGB2 has been detected in the blood and other biological fluids, it might be necessary to target HMGB2 at the same time as HMGB1 for therapeutical efficacy. ..