Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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HMG high mobility group

SMART accession number:	SM00398
Description:
Interpro abstract (IPR009071):	High mobility group (HMG) box domains are involved in binding DNA, and may be involved in protein-protein interactions as well. The structure of the HMG-box domain consists of three helices in an irregular array. HMG-box domains are found in one or more copies in HMG-box proteins, which form a large, diverse family involved in the regulation of DNA-dependent processes such as transcription, replication, and strand repair, all of which require the bending and unwinding of chromatin. Many of these proteins are regulators of gene expression. HMG-box proteins are found in a variety of eukaryotic organisms, and can be broadly divided into two groups, based on sequence-dependent and sequence-independent DNA recognition; the former usually contain one HMG-box motif, while the latter can contain multiple HMG-box motifs. HMG-box domains can be found in single or multiple copies in the following protein classes: HMG1 and HMG2 non-histone components of chromatin; SRY (sex determining region Y protein) involved in differential gonadogenesis; the SOX family of transcription factors [(PUBMED:12920151)]; sequence-specific LEF1 (lymphoid enhancer binding factor 1) and TCF-1 (T-cell factor 1) involved in regulation of organogenesis and thymocyte differentiation [(PUBMED:10890911)]; structure-specific recognition protein SSRP involved in transcription and replication; MTF1 mitochondrial transcription factor; nucleolar transcription factors UBF 1/2 (upstream binding factor) involved in transcription by RNA polymerase I; Abf2 yeast ARS-binding factor [(PUBMED:11779632)]; yeast transcription factors lxr1, Rox1, Nhp6b and Spp41; mating type proteins (MAT) involved in the sexual reproduction of fungi [(PUBMED:12781674)]; and the YABBY plant-specific transcription factors.
GO function:	protein binding (GO:0005515)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 5176 HMG domains in 4365 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a HMG domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with HMG domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Cellular role (predicted cellular role)

• Binding / catalysis: DNA-binding

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Aravind L, Landsman D
  • AT-hook motifs identified in a wide variety of DNA-binding proteins.
  • Nucleic Acids Res. 1998; 26: 4413-21
  • Display abstract

  • The AT-hook is a small DNA-binding protein motif which was first described in the high mobility group non-histone chromosomal protein HMG-I(Y). Since its discovery, this motif has been observed in other DNA-binding proteins from a wide range of organisms. Using pattern searches and position-dependent matrices, we have extracted the AT-hook motifs present in a non-redundant protein sequence database. We have classified these motifs into three types according to their sequence similarity and have found that they are prevalent in many eukaryotic nuclear proteins in single or multiple copies. Furthermore, AT-hook motifs are frequently associated with known functional domains seen in chromatin proteins and in DNA-binding proteins (e.g. histone folds, homeodomains and zinc fingers). In general, it appears that the AT-hook motif is an auxiliary protein motif cooperating with other DNA-binding activities and facilitating changes in the structure of the DNA either as a polypeptide on its own [e.g. HMG-I(Y)] or as part of a multidomain protein [e.g. Swi2p in Saccharomyces cerevisiae or HRX (ALL-1) in Homo sapiens]. It is most interesting that this motif seems to be quite specific to known or predicted chromosomal/DNA-binding proteins, suggesting that it may act as a versatile minor groove tether.

  • Grosschedl R, Giese K, Pagel J
  • HMG domain proteins: architectural elements in the assembly of nucleoprotein structures.
  • Trends Genet. 1994; 10: 94-100
  • Display abstract

  • The high-mobility group (HMG) domain is a DNA-binding motif that is shared abundant non-histone components of chromatin and by specific regulators of transcription and cell differentiation. The HMG family of proteins comprises members with multiple HMG domains that bind DNA with low sequence specificity, and members with single HMG domains that recognize specific nucleotide sequences. Common properties of HMG domain proteins include interaction with the minor groove of the DNA helix, binding to irregular DNA structures, and the capacity to modulate DNA structure by bending. DNA bending induced by the HMG domain can facilitate the formation of higher-order nucleoprotein complexes, suggesting that HMG domain proteins may have an architectural role in assembling such complexes.

  • Weir HM, Kraulis PJ, Hill CS, Raine AR, Laue ED, Thomas JO
  • Structure of the HMG box motif in the B-domain of HMG1.
  • EMBO J. 1993; 12: 1311-9
  • Display abstract

  • The conserved, abundant chromosomal protein HMG1 consists of two highly homologous, folded, basic DNA-binding domains, each of approximately 80 amino acid residues, and an acidic C-terminal tail. Each folded domain represents an 'HMG box', a sequence motif recently recognized in certain sequence-specific DNA-binding proteins and which also occurs in abundant HMG1-like proteins that bind to DNA without sequence specificity. The HMG box is defined by a set of highly conserved residues (most distinctively aromatic and basic) and appears to define a novel DNA-binding structural motif. We have expressed the HMG box region of the B-domain of rat HMG1 (residues 88-164 of the intact protein) in Escherichia coli and we describe here the determination of its structure by 2D 1H-NMR spectroscopy. There are three alpha-helices (residues 13-29, 34-48 and 50-74), which together account for approximately 75% of the total residues and contain many of the conserved basic and aromatic residues. Strikingly, the molecule is L-shaped, the angle of approximately 80 degrees between the two arms being defined by a cluster of conserved, predominantly aromatic, residues. The distinctive shape of the HMG box motif, which is distinct from hitherto characterized DNA-binding motifs, may be significant in relation to its recognition of four-way DNA junctions.

  • Lilley DM
  • DNA--protein interactions. HMG has DNA wrapped up.
  • Nature. 1992; 357: 282-3

  • Reeves R, Nissen MS
  • The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure.
  • J Biol Chem. 1990; 265: 8573-82
  • Display abstract

  • We have determined the domains of the mammalian high mobility group (HMG)I chromosomal proteins necessary and sufficient for binding to the narrow minor groove of stretches of A.T-rich DNA. Three highly conserved regions within each of the known HMG-I proteins is closely related to the consensus sequence T-P-K-R-P-R-G-R-P-K-K. A synthetic oligopeptide corresponding to this consensus "binding domain" (BD) sequence specifically binds to substrate DNA in a manner similar to the intact HMG-I proteins. Molecular Corey-Pauling-Koltun model building and computer simulations employing energy minimization programs to predict structure suggest that the consensus BD peptide has a secondary structure similar to the antitumor and antiviral drugs netropsin and distamycin and to the dye Hoechst 33258. In vitro these ligands, which also preferentially bind to A.T-rich DNA, have been demonstrated to effectively compete with both the BD peptide and the HMG-I proteins for DNA binding. The BD peptide also contains novel structural features such as a predicted Asx bend or "hook" at its amino-terminal end and laterally projecting cationic Arg/Lys side chains or "bristles" which may contribute to the binding properties of the HMG-I proteins. The predicted BD peptide structure, which we refer to as the "A.T-hook," represents a previously undescribed DNA-binding motif capable of binding to the minor groove of stretches of A.T base pairs.

  • Goodwin GH, Sanders C, Johns EW
  • A new group of chromatin-associated proteins with a high content of acidic and basic amino acids.
  • Eur J Biochem. 1973; 38: 14-9
• Disease (disease genes where sequence variants are found in this domain)

• SwissProt sequences and OMIM curated human diseases associated with missense mutations within the HMG domain.

  Protein	Disease
  Transcription factor SOX-9 (P48436) (SMART)	OMIM:114290: Campomelic dysplasia with autosomal sex reversal
  Sex-determining region Y protein (Q05066) (SMART)	OMIM:480000: Gonadal dysgenesis, XY type

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 14.60 map04310 Wnt signaling pathway 10.62 map04520 Adherens junction 10.62 map05216 Thyroid cancer 10.62 map05210 Colorectal cancer 10.62 map05213 Endometrial cancer 10.62 map05221 Acute myeloid leukemia 10.62 map05217 Basal cell carcinoma 10.62 map04916 Melanogenesis 10.62 map05215 Prostate cancer 0.44 map00190 Oxidative phosphorylation This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with HMG domain which could be assigned to a KEGG orthologous group, and not all proteins containing HMG domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of HMG domains in PDB

  PDB code	Main view	Title
  1aab		Nmr structure of rat hmg1 hmga fragment
  1cg7		Hmg protein nhp6a from saccharomyces cerevisiae
  1ckt		Crystal structure of hmg1 domain a bound to a cisplatin- modified dna duplex
  1e7j		Hmg-d complexed to a bulge dna
  1gt0		Crystal structure of a pou/hmg/dna ternary complex
  1hma		The solution structure and dynamics of the dna binding domain of hmg-d from drosophila melanogaster
  1hme		Structure of the hmg box motif in the b-domain of hmg1
  1hmf		Structure of the hmg box motif in the b-domain of hmg1
  1hry		The 3d structure of the human sry-dna complex solved by multid-dimensional heteronuclear-edited and-filtered nmr
  1hrz		The 3d structure of the human sry-dna complex solved by multi-dimensional heteronuclear-edited and-filtered nmr
  1hsm		The structure of the hmg box and its interaction with dna
  1hsn		The structure of the hmg box and its interaction with dna
  1i11		Solution structure of the dna binding domain, sox-5 hmg box from mouse
  1j3c		Solution structure of the c-terminal domain of the hmgb2
  1j3d		Solution structure of the c-terminal domain of the hmgb2
  1j3x		Solution structure of the n-terminal domain of the hmgb2
  1j46		3d solution nmr structure of the wild type hmg-box domain of the human male sex determining factor sry complexed to dna
  1j47		3d solution nmr structure of the m9i mutant of the hmg-box domain of the human male sex determining factor sry complexed to dna
  1j5n		Solution structure of the non-sequence-specific hmgb protein nhp6a in complex with sry dna
  1k99		Solution structure of the first hmg box in human upstream binding factor
  1l8y		Solution structure of hmg box 5 in human upstream binding factor
  1l8z		Solution structure of hmg box 5 in human upstream binding factor
  1lwm		Solution structure of the sequence-non-specific hmgb protein nhp6a
  1nhm		The structure of the hmg box and its interaction with dna
  1nhn		The structure of the hmg box and its interaction with dna
  1o4x		Ternary complex of the dna binding domains of the oct1 and sox2 transcription factors with a 19mer oligonucleotide from the hoxb1 regulatory element
  1qrv		Crystal structure of the complex of hmg-d and dna
  1v63		Solution structure of the 6th hmg box of mouse ubf1
  1v64		Solution structure of the 3rd hmg box of mouse ubf1
  1wgf		Solution structure of the 4th hmg-box of mouse ubf1
  1wxl		Solution structure of the hmg-box domain in the ssrp1 subunit of fact
  1wz6		Solution structure of the hmg_box domain of murine bobby sox homolog
  2co9		Solution structure of the hmg_box domain of thymus high mobility group box protein tox from mouse
  2crj		Solution structure of the hmg domain of mouse hmg domain protein hmgx2
  2cs1		Solution structure of the hmg domain of human dna mismatch repair protein
  2d7l		Solution structure of the hmg box domain from human wd repeat and hmg-box dna binding protein 1
  2e6o		Solution structure of the hmg box domain from human hmg-box transcription factor 1
  2eqz		Solution structure of the first hmg-box domain from high mobility group protein b3
  2gzk		Structure of a complex of tandem hmg boxes and dna
  2hdz		Crystal structure analysis of the ubf hmg box5
  2lef		Lef1 hmg domain (from mouse), complexed with dna (15bp), nmr, 12 structures
  2yqi		Solution structure of the second hmg-box domain from high mobility group protein b3
  2yrq		Solution structure of the tandem hmg box domain from human high mobility group protein b1
  2yuk		Solution structure of the hmg box of human myeloid/lymphoid or mixed-lineage leukemia protein 3 homolog
  2yul		Solution structure of the hmg box of human transcription factor sox-17
  3f27		Structure of sox17 bound to dna
  3fgh		Human mitochondrial transcription factor a box b

• Links (links to other resources describing this domain)

• PFAM	HMG_box
  INTERPRO	IPR009071

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