PROSITE documentation PDOC00305

HMG boxes A and B DNA-binding domains signature and profile

High mobility group (HMG) chromosomal proteins are a family of relatively low molecular weight non-histone components that bind DNA without sequence specificity. HMG1 (also called HMG-T in fish) and HMG2 are related proteins that have two distinguishing features: two HMG boxes (A and B), homologous folded domains of around 80 amino acid residues, and a long acidic tail containing 20 to 30 aspartic or glutamic acid residues [1,2]. The HMG box A is only found in HMG 1 and 2 proteins whereas the HMG box B is also present in various transcription factors. HMG boxes have unusual DNA binding activity. They bind preferentially to distorted DNAs, such as four-way junctions, kinked cisplatin-modified DNA, DNA bulges, and have the property to bend DNA [2]. They can bind DNA without sequence specificity like in HMG1 and 2 or recognize a specific site.

Several structures of HMG-boxes have been solved (see <PDB:1AAB>) [3,4]. They have a common fold consisting of three α helices arranged in an "L-shape". The HMG box binds DNA through its concave face to the minor groove of B-form DNA and causes bending by partial intercalation of a hydrophobic residue close to the N-terminus of helix I [4,5].

Some proteins known to contain a HMG box are listed below:

• Eukaryotic HMG1, HMG2 and related proteins.
• Animal sex determining region Y (SRY) and related proteins, a transcriptional activator which regulates a genetic switch in male development.
• Animal SOX family of transcription factors, a conserved family of proteins related to the testis-determining factor SRY.
• Mammalian lymphoid enhancer binding factor 1 (LEF1), a transcriptional activator which regulates a genetic switch in male development.
• Eukaryotic structure-specific recognition protein 1 (SSRP). It binds specifically to double-stranded and, at low levels, to single-stranded DNA which has been modified by the anticancer drug cisplatin.
• Mitochondrial transcription factor 1 (MTF1). It confers selective promoter recognition on the core subunit of the yeast mitochondrial RNA polymerase.
• Vertebrate nucleolar transcription factors (UBF1/2). They recognize the ribosomal RNA gene promoter and activate transcription mediated by RNA polymerase I.
• Yeast ARS-binding factor (ABF2). It binds specifically to the autonomously replicating sequence 1 (ARS1).
• Yeast transcription factors IXR1, ROX1, NHP6A/B, SPP41.
• Drosophila capicua protein. A transcription cofactor involved in negative regulation of transcription.
• Fission yeast mismatch binding protein 1 (cmb1). It binds to cytosines in base mismatches and opposite chemically altered guanines.
• Tetrahymena thermophila micronuclear linker histone polyprotein (MIC LH).
• Mammalian nuclear autoantigen Speckled 100 kDa protein (Sp-100).

The pattern we developed covers the second helix of the HMG box A and therefore is specific for HMG1/2 proteins. We also developed a profile that covers the whole domain and recognizes both types of HMG boxes.