High Mobility Group (HMG) Proteins Michael Bustin, Ph.D., 
Chief, Protein Section, LM, CCR, NCI, NIH
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HMGs are ubiquitous nuclear proteins that regulate and facilitate various DNA-related activities such as transcription, replication, recombination, and repair.  They bind to DNA and chromatin and act as "architectural elements" that induce both short- and long-range changes in the structure of their binding sites. They affect the activities of various regulatory molecules including hormone receptors, p53, the RAG proteins involved in V(D)J recombination, the homeotic protein HOXD9, of HIV integrase, and several transcription factors. The functional motifs of the ubiquitous HMG proteins are widespread and found in the DNA binding domains of numerous regulatory proteins.

HMG proteins may play a significant role in human disorders. Disruptions and rearrangementsin the genes coding for some of the HMG proteins are associated with the etiology of verycommon benign tumors such as Uterine leiomyomas, Endometrial polyps, Lipomas. HMG-1 and HMG-2 proteins areimplicated in the mechanism of action ofthe anti-cancer drug cis-platinum. In addition, antibodies to HMG proteins are found in patients suffering from autoimmune diseases. 

Thus, by modifying the architecture of DNA and chromatin the HMG proteinsmay contribute to the regulation of various processes which ultimately affect the cellular phenotype. Studies on the structure and function oftheseproteins may provide insights into the molecular mechanisms underlying the etiology of certain diseases.


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The High Mobility Group (HMG) proteins were originally isolated from mammalian  cells  and arbitrarily classed as a specific type of nonhistones based on the observation that they are present in all mammalian and many vertebrate cells, that they share certain physical properties, and that they are associated with isolated chromatin. They were subdivided into 3 groups named HMG-1/-2, HMG-14/-17 and HMG-I/Y. These proteins are considered as the Canonical HMG proteins. Subsequent studies revealed that the functional motifs characteristic of each of the canonical HMG proteins are widespread among nuclear proteins. Proteins containing any of the functional motifs of the canonical HMG proteins are called HMG-motif proteins. In fact, the canonical HMG proteins can be considered to be a subclass of the HMG-motif proteins. The HMG motif proteins are now subdivided into 3 superfamilies which are now named: 1.  HMGB (previous name HMG-1/-2), 2. HMGN (previous name HMG-14/-17) and 3. HMGA (previous name HMG-I/Y/C). Each HMG family has a characteristic functional sequence motif.  The functional motif of the HMGB family is named “HMG-box”, that of the HMGN family is named “nucleosomal binding domain”, and that of the HMGA family is named “AT-hook”. Proteins containing any of these functional motifs embedded in their sequence are known as “HMG-motif proteins”.   The interrelationship between the various HMG proteins is diagrammed below. 

For more details and a list of HMG proteins, please see the HMG-nomenclature Web page


HMG Proteins


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Bustin, M: Regulation of DNA-dependent Activities by the Functional Motifs of the HMG Chromosomal Proteins. Mol. Cell Biol. 19: 5237-5246, 1999.

Bustin, M. and Reeves, R.: HMG chromosomal proteins: Architectural components that facilitate chromatin function. Progress in Nucleic Acid Research and Molecular Biology (K. Moldave and W. Cohn editors) vol 54: 35-100, 1996.

The HMG Chromosomal Proteins, E.W. Johns (editor). Academic Press, 1982.

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Home HMG Proteins  |  Research Goals  |  Knock-out mice... 


chromatin unfolding...  |  Intracellular Trafficking...  |   Organization of HMG...
New HMG...  |  Linker Histone...  |  Modifications...  |  Development...




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Last revised on March 20, 2003 by Linda G. Byrd, Ph.D.

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