hmg box domains


Summary: DNA-binding domains present in proteins of the HMG-box superfamily including the archetypal HMGB PROTEINS, a number of sequence specific TRANSCRIPTION FACTORS, and other DNA-BINDING PROTEINS. The domains consist of 70-80 amino acids that form an L-shaped fold from three alpha-helical segments. The domain has the capacity to recognize and/or induce specific DNA structures and effect the accessibility of the DNA to other proteins involved in transcription, recombination, or DNA repair. (Note that not all HIGH MOBILITY GROUP PROTEINS contain this domain.)

Top Publications

  1. Stros M, Launholt D, Grasser K. The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins. Cell Mol Life Sci. 2007;64:2590-606 pubmed
    ..Compared to plants, human cells contain a larger variety of HMG-box proteins. Whereas in humans transcription factors are the most divergent group of HMG-box proteins, in plants the chromosomal HMGB-type proteins are most variable. ..
  2. Stefanovsky V, Moss T. The splice variants of UBF differentially regulate RNA polymerase I transcription elongation in response to ERK phosphorylation. Nucleic Acids Res. 2008;36:5093-101 pubmed publisher
    ..Thus, UBF2 functionally simulates a hemi-phosphorylated UBF whose expression may provide a means by which to tune the response of the ribosomal RNA genes to growth factor stimulation. ..
  3. Kajino K, Yamamoto T, Hayashi J, Umeda T, Takahara T, Hino O. Recombination hot spot of hepatitis B virus genome binds to members of the HMG domain protein family and the Y box binding protein family; implication of these proteins in genomic instability. Intervirology. 2001;44:311-6 pubmed
    ..We report them here because several documents have already suggested the possible association of these families and DNA recombination. ..
  4. Koopman P, Schepers G, Brenner S, Venkatesh B. Origin and diversity of the SOX transcription factor gene family: genome-wide analysis in Fugu rubripes. Gene. 2004;328:177-86 pubmed publisher
  5. Galay Burgos M, Llewellyn L, Mylonas C, Canario A, Zanuy S, Sweeney G. Analysis of the Sox gene family in the European sea bass (Dicentrarchus labrax). Comp Biochem Physiol B Biochem Mol Biol. 2004;137:279-84 pubmed
    ..The cloned Sox genes are members of the SoxB, SoxC, SoxE and SoxF groups. Sequence analysis shows that some of the clones represent genes duplicated in sea bass with respect to the mammalian Sox gene family. ..
  6. Jager M, Quéinnec E, Houliston E, Manuel M. Expansion of the SOX gene family predated the emergence of the Bilateria. Mol Phylogenet Evol. 2006;39:468-77 pubmed
    ..In contrast, gene loss appears to have occurred in the nematode and probably in other protostome lineages, explaining their lower number of SOX genes. ..
  7. Matsuzawa Watanabe Y, Inoue J, Semba K. Transcriptional activity of testis-determining factor SRY is modulated by the Wilms' tumor 1 gene product, WT1. Oncogene. 2003;22:7900-4 pubmed
    ..These results suggest that WT1 forms a complex with SRY to regulate transcription and that this WT1-SRY interaction is important in testis development...
  8. Phillips N, Jancso Radek A, Ittah V, Singh R, Chan G, Haas E, et al. SRY and human sex determination: the basic tail of the HMG box functions as a kinetic clamp to augment DNA bending. J Mol Biol. 2006;358:172-92 pubmed
    ..We speculate that the kinetic stability of a bent DNA complex is critical to the assembly and maintenance of a sex-specific transcriptional pre-initiation complex. ..
  9. Gontan C, Guttler T, Engelen E, Demmers J, Fornerod M, Grosveld F, et al. Exportin 4 mediates a novel nuclear import pathway for Sox family transcription factors. J Cell Biol. 2009;185:27-34 pubmed publisher
    ..This suggests that nuclear import of Sox proteins is facilitated by several parallel import pathways. ..

More Information


  1. Dragan A, Carrillo R, Gerasimova T, Privalov P. Assembling the human IFN-beta enhanceosome in solution. J Mol Biol. 2008;384:335-48 pubmed publisher
  2. Hossain M, Hosokawa H, Hasegawa A, Watarai H, Taniguchi M, Yamashita M, et al. Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cells. Immunology. 2008;125:377-86 pubmed publisher
    ..These results suggest that LEF-1 is involved in the GATA-3 complex, while also regulating the GATA-3 function, such as the induction of Th2 cytokine expression via the inhibition of the DNA-binding activity of GATA-3. ..
  3. Shi L, Yue W, Ren Y, Lei F, Zhao J. Sex determination in goat by amplification of the HMG box using duplex PCR. Anim Reprod Sci. 2008;105:398-403 pubmed
    ..Thus, this study showed that this duplex PCR method can be applied to sex the goat pre-implantation embryos and to manipulate the sex ratio of offspring in goat breeding programs. ..
  4. Aronstein K, Murray K, De Leon J, Qin X, Weinstock G. High mobility group (HMG-box) genes in the honeybee fungal pathogen Ascosphaera apis. Mycologia. 2007;99:553-61 pubmed
    ..This new method allows for identification of a single mating type idiomorph and might become an essential tool for applied and basic research of chalkbrood disease in honeybees...
  5. Kanamori M, Kato H, Yasuda N, Koizumi S, Peever T, Kamakura T, et al. Novel mating type-dependent transcripts at the mating type locus in Magnaporthe oryzae. Gene. 2007;403:6-17 pubmed
    ..A CT dinucleotide repeat, (CT)n, present in the upstream region of MAT1-1-3, was polymorphic among the isolates. ..
  6. Marchina E, Gambera A, Spinelli E, Clerici P, Scagliola P, Sartori E, et al. Identification of a new mutation in the SRY gene in a 46,XY woman with Swyer syndrome. Fertil Steril. 2009;91:932.e7-932.e11 pubmed publisher
    ..Clinical and endocrinologic data are reported. This is a new rare case of a single nucleotide insertion affecting the SRY gene in 46,XY females with sex reversal. This new mutation should be considered in genetic counseling. ..
  7. Grasser M, Lentz A, Lichota J, Merkle T, Grasser K. The Arabidopsis genome encodes structurally and functionally diverse HMGB-type proteins. J Mol Biol. 2006;358:654-64 pubmed
    ..In summary, our data demonstrate (i) that plant HMGB-type proteins are functionally variable and (ii) that it is difficult to predict HMG-box function solely based on sequence similarity. ..
  8. Prashant -, Gour D, Dubey P, Jain A, Gupta S, Joshi B, et al. Sex determination in 6 bovid species by duplex PCR. J Appl Genet. 2008;49:379-81 pubmed publisher
    ..The protocol was subjected to a blind test that showed a 100 percent specificity and accuracy, thus it can be used in sex determination in livestock breeding programs. ..
  9. Sanij E, Poortinga G, Sharkey K, Hung S, Holloway T, Quin J, et al. UBF levels determine the number of active ribosomal RNA genes in mammals. J Cell Biol. 2008;183:1259-74 pubmed publisher
    ..We also show that the active rRNA gene pool is not static but decreases during differentiation, correlating with diminished UBF expression. Thus, UBF1 levels regulate active rRNA gene chromatin during growth and differentiation. ..
  10. Wilson M, Yang K, Kalousova A, Lau J, Kosaka Y, Lynn F, et al. The HMG box transcription factor Sox4 contributes to the development of the endocrine pancreas. Diabetes. 2005;54:3402-9 pubmed
    ..We show here that several Sox transcription factors are expressed in the developing pancreas and in the islet, and that one of these factors, Sox4, is required for the normal development of pancreatic islets. ..
  11. Jakubiczka S, Bettecken T, Koch G, Tuysuz B, Wollnik B, Wieacker P. Campomelic dysplasia without sex reversal in a Turkish patient is due to mutation Ala119Val within the SOX9 gene. Clin Dysmorphol. 2001;10:197-201 pubmed
    ..The same mutation was recently reported in a patient with 46,XX karyotype. Additionally, our patient is homozygous for the common polymorphism c507C-->T, while both parents are heterozygous. ..
  12. Bergeron S, Madathiparambil T, Swanson P. Both high mobility group (HMG)-boxes and the acidic tail of HMGB1 regulate recombination-activating gene (RAG)-mediated recombination signal synapsis and cleavage in vitro. J Biol Chem. 2005;280:31314-24 pubmed
    ..Box A or B mutants fail to promote RAG synaptic complex formation, but this defect is alleviated when the acidic tail is removed from these mutants. ..
  13. Hett A, Ludwig A. SRY-related (Sox) genes in the genome of European Atlantic sturgeon (Acipenser sturio). Genome. 2005;48:181-6 pubmed
    ..In a phylogenetic analysis (neighbor-joining, maximum likelihood, maximum parsimony), these genes clustered with their mouse orthologues. In the case of Sox4, Sox17, and Sox21, we found evidence of gene duplication. ..
  14. Jacobi V, Dufour J, Bouvet G, Aoun M, Bernier L. Identification of transcripts up-regulated in asexual and sexual fruiting bodies of the Dutch elm disease pathogen Ophiostoma novo-ulmi. Can J Microbiol. 2010;56:697-705 pubmed publisher
    ..novo-ulmi and should be of interest to researchers concerned with reproduction, mating type, and sexuality of filamentous ascomycete fungi. ..
  15. Goff D, Nilson L, Morisato D. Establishment of dorsal-ventral polarity of the Drosophila egg requires capicua action in ovarian follicle cells. Development. 2001;128:4553-62 pubmed
    ..Our experiments reveal that cic controls dorsal-ventral patterning by regulating pipe expression in ovarian follicle cells, before its previously described role in interpreting the Dorsal gradient. ..
  16. Assumpção J, Benedetti C, Maciel Guerra A, Guerra G, Baptista M, Scolfaro M, et al. Novel mutations affecting SRY DNA-binding activity: the HMG box N65H associated with 46,XY pure gonadal dysgenesis and the familial non-HMG box R30I associated with variable phenotypes. J Mol Med (Berl). 2002;80:782-90 pubmed
    ..The R30I mutation is located upstream to the HMG box, within the (29)RRSSS(33) phosphorylation site. The E. coli expressed SRY(R30I) protein was poorly phosphorylated and consequently showed reduced DNA-binding capacity in vitro...
  17. Barve M, Arie T, Salimath S, Muehlbauer F, Peever T. Cloning and characterization of the mating type (MAT) locus from Ascochyta rabiei (teleomorph: Didymella rabiei) and a MAT phylogeny of legume-associated Ascochyta spp. Fungal Genet Biol. 2003;39:151-67 pubmed
    ..A. rabiei on chickpea is phylogenetically distant from other legume-associated Ascochyta spp. and the specific status of A. rabiei, A. lentis, A. pisi, and A. fabae was confirmed by the HMG phylogeny ..
  18. Stemmer C, Fernandez S, Lopez G, Alonso J, Grasser K. Plant chromosomal HMGB proteins efficiently promote the bacterial site-specific beta-mediated recombination in vitro and in vivo. Biochemistry. 2002;41:7763-70 pubmed
  19. Taguchi S, Tagawa K, Humphreys T, Satoh N. Group B sox genes that contribute to specification of the vertebrate brain are expressed in the apical organ and ciliary bands of hemichordate larvae. Zoolog Sci. 2002;19:57-66 pubmed
  20. Xu Y, Yang W, Wu J, Shi Y. Solution structure of the first HMG box domain in human upstream binding factor. Biochemistry. 2002;41:5415-20 pubmed
    ..It contains six HMG box domains; the HMG box is a minor groove DNA-binding domain that has been found in hundreds of proteins with different ..
  21. Taudte S, Xin H, Bell A, Kallenbach N. Interactions between HMG boxes. Protein Eng. 2001;14:1015-23 pubmed
    ..By contrast, the ABA triple subdomain construct is partially unfolded and is less active than individual boxes or di-domains. Thus, long-range inter-domain effects can influence the activity of HMG boxes. ..
  22. Cho J, Lee Y, Chae C. The modulation of the biological activities of mitochondrial histone Abf2p by yeast PKA and its possible role in the regulation of mitochondrial DNA content during glucose repression. Biochim Biophys Acta. 2001;1522:175-86 pubmed
  23. Schmidt M, Patterson M, Farrell E, Munsterberg A. Dynamic expression of Lef/Tcf family members and beta-catenin during chick gastrulation, neurulation, and early limb development. Dev Dyn. 2004;229:703-7 pubmed
  24. Yuan F, Gu L, Guo S, Wang C, Li G. Evidence for involvement of HMGB1 protein in human DNA mismatch repair. J Biol Chem. 2004;279:20935-40 pubmed
    ..Evidence is also presented that HMGB1 physically interacts with MutSalpha and is required at a step prior to the excision of mispaired nucleotide in mismatch repair. ..
  25. Kawase T, Sato K, Ueda T, Yoshida M. Distinct domains in HMGB1 are involved in specific intramolecular and nucleosomal interactions. Biochemistry. 2008;47:13991-6 pubmed publisher
    ..These results suggest that the acidic tail modulates the biological functions of HMGB1 through these specific interactions. ..
  26. Hansen F, Madsen C, Nordland A, Grasser M, Merkle T, Grasser K. A novel family of plant DNA-binding proteins containing both HMG-box and AT-rich interaction domains. Biochemistry. 2008;47:13207-14 pubmed publisher
    ..Therefore, both DNA-binding domains contribute to the DNA interactions of ARID-HMG1. Accordingly, the protein combines DNA-binding properties characteristic of ARID and HMG-box proteins. ..
  27. 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 proteins are composed of one or two conserved HMG box domains, each forming three alpha-helices that fold into a sequence-nonspecific DNA-binding module recognizing the ..
  28. 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. ..
  29. Bouvier B, Lavery R. A free energy pathway for the interaction of the SRY protein with its binding site on DNA from atomistic simulations. J Am Chem Soc. 2009;131:9864-5 pubmed publisher
    ..The resulting free energy profile provides a detailed view of protein-DNA binding and identifies a metastable intermediate state. ..
  30. Sánchez Moreno I, Coral Vazquez R, Mendez J, Canto P. Full-length SRY protein is essential for DNA binding. Mol Hum Reprod. 2008;14:325-30 pubmed publisher
    ..We demonstrate the importance that full-length SRY has, particularly the C-terminal region of the protein, in DNA binding in vitro. Likewise, the affinity of the HMG box alone is clearly reduced when compared with the full-length SRY. ..
  31. Jordan B, Jain M, Natarajan S, Frasier S, Vilain E. Familial mutation in the testis-determining gene SRY shared by an XY female and her normal father. J Clin Endocrinol Metab. 2002;87:3428-32 pubmed
    ..The allelic variant of SRY transmitted in this family and shared by both a phenotypic female (proband) and a phenotypic male (proband's father) emphasizes the importance of modifier genes in the sex determination pathway. ..
  32. Shahid M, Dhillon V, Hussain Z, Masa J, Aslam M, Raish M, et al. Analysis of the SRY gene in two sex-reversed XY sisters identifies two new novel point mutations in the high mobility group box domain. Fertil Steril. 2008;90:1199.e1-8 pubmed publisher
  33. Wozniak K, Błasiak J. Recognition and repair of DNA-cisplatin adducts. Acta Biochim Pol. 2002;49:583-96 pubmed
    ..The formation of complexes between DNA and proteins in the presence of cisplatin and the changes in the cell architecture may account for the drug cytotoxicity. ..
  34. Grasser M, Christensen J, Peterhansel C, Grasser K. Basic and acidic regions flanking the HMG-box domain of maize HMGB1 and HMGB5 modulate the stimulatory effect on the DNA binding of transcription factor Dof2. Biochemistry. 2007;46:6375-82 pubmed
    ..Interestingly, recombinant HMGB protein variants that have a relatively low affinity for linear DNA (such as proteins lacking the basic N-terminal domain) efficiently assist Dof2-DNA binding. ..
  35. O Flaherty E, Kaye J. TOX defines a conserved subfamily of HMG-box proteins. BMC Genomics. 2003;4:13 pubmed
    ..In addition, our data suggest that the TOX subtype of HMG-box domain first appeared in invertebrates, was duplicated in early vertebrates and likely took on new functions in mammalian species. ..
  36. Novakova O, Kasparkova J, Malina J, Natile G, Brabec V. DNA-protein cross-linking by trans-[PtCl(2)(E-iminoether)(2)]. A concept for activation of the trans geometry in platinum antitumor complexes. Nucleic Acids Res. 2003;31:6450-60 pubmed
  37. Unoshima M. [Therapeutic effect of anti-HMGB1 antibody and anti-RAGE antibody on SIRS/sepsis]. Nihon Rinsho. 2004;62:2323-9 pubmed
    ..Treatment of anti-HMGB1 or anti-RAGE antibody seems to be valid therapy against SIRS/sepsis. ..
  38. Shahid M, Dhillon V, Aslam M, Husain S. Three new novel point mutations localized within and downstream of high-mobility group-box region in SRY gene in three Indian females with Turner syndrome. J Clin Endocrinol Metab. 2005;90:2429-35 pubmed
    ..Lack of a second sex chromosome in a majority of cells [mosaic karyotype and mutation(s) in the SRY gene] in these patients may have triggered the short stature. ..
  39. Zhang X, Zhang J, Li X, Xu J, Huang H, Chen Q, et al. Compact molten globule-like state of hUBF HMG Box1 at extremely low pH. Biochim Biophys Acta. 2005;1748:66-73 pubmed
    ..All these data suggest that the A state of hUBF HMG Box1 could represent a potential folding intermediate on protein folding pathway. ..
  40. Zhang X, Xu Y, Zhang J, Wu J, Shi Y. Structural and dynamic characterization of the acid-unfolded state of hUBF HMG box 1 provides clues for the early events in protein folding. Biochemistry. 2005;44:8117-25 pubmed
    ..On the basis of the results presented herein, we propose a potential protein-folding pathway on which these residual structures play a role of initiation site in the early folding stages. ..
  41. Paoletti M, Buck K, Brasier C. Cloning and sequence analysis of the MAT-B (MAT-2) genes from the three Dutch elm disease pathogens, Ophiostoma ulmi, O. novo-ulmi, and O. himal-ulmi. Mycol Res. 2005;109:983-91 pubmed
    ..The 3' flanking regions have been shown to contain variable numbers of repeated oligonucleotide sequences, the number of which is species-specific and readily distinguished by a simple PCR assay. ..
  42. Savare J, Girard F. [SUMO modification represses transcriptional activity of Sox proteins]. Med Sci (Paris). 2005;21:917-9 pubmed
  43. Luster T, Rizzino A. Regulation of the FGF-4 gene by a complex distal enhancer that functions in part as an enhanceosome. Gene. 2003;323:163-72 pubmed
    ..In contrast, the HMG motif identified in this study is only partially dependent on the other enhancer cis-regulatory elements for its function. ..
  44. Rau D, Maier F, Papa R, Brown A, Balmas V, Saba E, et al. Isolation and characterization of the mating-type locus of the barley pathogen Pyrenophora teres and frequencies of mating-type idiomorphs within and among fungal populations collected from barley landraces. Genome. 2005;48:855-69 pubmed
    ..Overall, sexual reproduction appears to be the major process that equalizes the frequencies of the 2 mating types within populations. ..
  45. Yamada L, Kobayashi K, Degnan B, Satoh N, Satou Y. A genomewide survey of developmentally relevant genes in Ciona intestinalis. IV. Genes for HMG transcriptional regulators, bZip and GATA/Gli/Zic/Snail. Dev Genes Evol. 2003;213:245-53 pubmed
    ..The present comprehensive analysis therefore provides a means to study the role of these transcription factors in developmental processes of basal chordates. ..
  46. Harley V, Clarkson M, Argentaro A. The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]. Endocr Rev. 2003;24:466-87 pubmed
    ..Many genes, however, remain unidentified, because in the majority of cases of XY females and in all cases of XX males lacking SRY, the mutated gene is unknown. ..
  47. Boer B, Bernadt C, Desler M, Wilder P, Kopp J, Rizzino A. Differential activity of the FGF-4 enhancer in F9 and P19 embryonal carcinoma cells. J Cell Physiol. 2006;208:97-108 pubmed
  48. Wissmüller S, Kosian T, Wolf M, Finzsch M, Wegner M. The high-mobility-group domain of Sox proteins interacts with DNA-binding domains of many transcription factors. Nucleic Acids Res. 2006;34:1735-44 pubmed
    ..The HMG domain thus not only possesses DNA-binding and DNA-bending but also protein-interacting ability which may be equally important for the architectural function of Sox proteins on their target gene promoters. ..
  49. Zheng J, Zhu M. Isolation and sequence analysis of the Sox-1, -2, -3 homologs in Trionyx sinensis and Alligator sinensis having temperature-dependent sex determination. Biochem Genet. 2006;44:101-12 pubmed
  50. Stott K, Tang G, Lee K, Thomas J. Structure of a complex of tandem HMG boxes and DNA. J Mol Biol. 2006;360:90-104 pubmed
    The high-mobility group protein HMGB1 contains two tandem DNA-binding HMG box domains, A and B, linked by a short flexible linker that allows the two domains to behave independently in the free protein...
  51. Li Y, Oh H, Lau Y. The poly(ADP-ribose) polymerase 1 interacts with Sry and modulates its biological functions. Mol Cell Endocrinol. 2006;257-258:35-46 pubmed
    ..PARP-1 represses Sry-mediated transactivation of a reporter gene in cultured cells. Hence, PARP-1 could modulate the regulatory function(s) of Sry on its target genes in this developmental pathway. ..
  52. Shahid M, Dhillion V, Jain N, Hedau S, Diwakar S, Sachdeva P, et al. Two new novel point mutations localized upstream and downstream of the HMG box region of the SRY gene in three Indian 46,XY females with sex reversal and gonadal tumour formation. Mol Hum Reprod. 2004;10:521-6 pubmed
    ..Results suggest the involvement of SRY gene in sex reversal which further supports the relationship between SRY alterations, gonadal dysgenesis and/or primary infertility...
  53. Maffini M, Denes V, Sonnenschein C, SOTO A, Geck P. APRIN is a unique Pds5 paralog with features of a chromatin regulator in hormonal differentiation. J Steroid Biochem Mol Biol. 2008;108:32-43 pubmed
    ..The results indicate that APRIN, in addition to its Pds5 similarity, has the features and localization of a hormone-induced chromatin regulator. ..