High-Mobility Group or HMG is a group of chromosomal proteins that are involved in the regulation of DNA-dependent processes such as transcription, replication, recombination, and DNA repair. [1]
The HMG proteins are subdivided into 3 superfamilies each containing a characteristic functional domain:
Proteins containing any of these embedded in their sequence are known as HMG motif proteins. HMG-box proteins are found in a variety of eukaryotic organisms.
They were originally isolated from mammalian cells, and named according to their electrophoretic mobility in polyacrylamide gels. [2]
HMG proteins are thought to play a significant role in various human disorders. Disruptions and rearrangements in the genes coding for some of the HMG proteins are associated with some common benign tumors. Antibodies to HMG proteins are found in patients with autoimmune diseases. The SRY gene on the Y Chromosome, responsible for male sexual differentiation, contains an HMG-Box domain. A member of the HMG family of proteins, HMGB1, has also been shown to have an extracellular activity as a chemokine, attracting neutrophils and mononuclear inflammatory cells to the infected liver. [3] The high-mobility group protein such as HMO1 [4] alters DNA architecture by binding, bending and looping. Furthermore, these HMG-box DNA-binding proteins increase the flexibility of the DNA upon binding. [5]
In mammalian cells, the HMG non-histone proteins can modulate the activity of major DNA repair pathways including base excision repair, mismatch repair, nucleotide excision repair and double-strand break repair [6] .
DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that identify a base pair. However, there are some known minor groove DNA-binding ligands such as netropsin, distamycin, Hoechst 33258, pentamidine, DAPI and others.
Sex-determining region Y protein (SRY), or Testis-determining factor (TDF), is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in therian mammals. SRY is an intronless sex-determining gene on the Y chromosome. Mutations in this gene lead to a range of disorders of sex development with varying effects on an individual's phenotype and genotype.
HMGN proteins are members of the broader class of high mobility group (HMG) chromosomal proteins that are involved in regulation of transcription, replication, recombination, and DNA repair.
SOX genes encode a family of transcription factors that bind to the minor groove in DNA, and belong to a super-family of genes characterized by a homologous sequence called the HMG-box. This HMG box is a DNA binding domain that is highly conserved throughout eukaryotic species. Homologues have been identified in insects, nematodes, amphibians, reptiles, birds and a range of mammals. However, HMG boxes can be very diverse in nature, with only a few amino acids being conserved between species.
High-mobility group AT-hook 2, also known as HMGA2, is a protein that, in humans, is encoded by the HMGA2 gene.
High mobility group box 1 protein, also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.
High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.
Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the LEF1 gene. It's a member of T cell factor/lymphoid enhancer factor (TCF/LEF) family.
High-mobility group protein B2 also known as high-mobility group protein 2 (HMG-2) is a protein that in humans is encoded by the HMGB2 gene.
Non-histone chromosomal protein HMG-14 is a protein that in humans is encoded by the HMGN1 gene.
Transcription factor 7 is the gene that in humans encodes for the TCF1 protein.
Transcription factor SOX-8 is a protein that in humans is encoded by the SOX8 gene.
High mobility group nucleosome-binding domain-containing protein 3 is a protein that in humans is encoded by the HMGN3 gene.
Thymocyte selection-associated high mobility group box protein TOX is a protein that in humans is encoded by the TOX gene. TOX drives T-cell exhaustion and plays a role in innate lymphoid cell development.
In molecular biology, the HMG-box is a protein domain which is involved in DNA binding. The domain is composed of approximately 75 amino acid residues that collectively mediate the DNA-binding of chromatin-associated high-mobility group proteins. HMG-boxes are present in many transcription factors and chromatin-remodeling complexes, where they can mediate non-sequence or sequence-specific DNA binding.
The AT-hook is a DNA-binding motif present in many proteins, including the high mobility group (HMG) proteins, DNA-binding proteins from plants and hBRG1 protein, a central ATPase of the human switching/sucrose non-fermenting (SWI/SNF) remodeling complex.
The TCF/LEF family is a group of genes that encode transcription factors which bind to DNA through a SOX-like high mobility group domain. They are involved in the Wnt signaling pathway, particularly during embryonic and stem-cell development, but also had been found to play a role in cancer and diabetes. TCF/LEF factors recruit the coactivator beta-catenin to enhancer elements of genes they target. They can also recruit members of the Groucho family of corepressors.
High mobility group protein HMG14 and HMG17 also known as nucleosomal binding domain is a family of evolutionarily related proteins.
High mobility group nucleosome-binding domain-containing protein 4 is a transcription factor that in humans is encoded by the HMGN4 gene.