High Mobility Group (HMG) proteins

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High Mobility Group (HMG) proteins

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The HMG family contains a number of structurally and functionally related nonhistone chromatin-associated proteins. A nomenclature strategy (hosted by the Mouse Gene Initiative [5]) indicates that the family can be divided into 3 subdivisions, HMGA, HMGB and HMGN. The human genome has 11 genes for HMG family proteins; HMGA1-2, HMGB1-4 and HMGN1-5. The HMGs regulate DNA-dependent processes (transcription, replication, recombination) and DNA repair, and are important in development and disease [1-2,8].

Targets

3279

high mobility group box 1 Show summary »« Hide summary

Target Id

3279

Nomenclature

high mobility group box 1

Previous and unofficial names

amphoterin | HMG1 | sulfoglucuronyl carbohydrate binding protein

Genes

HMGB1 (Hs), Hmgb1 (Mm), Hmgb1 (Rn)

Ensembl ID

ENSG00000189403 (Hs), ENSMUSG00000066551 (Mm)

UniProtKB AC

P09429 (Hs), P07155 (Mm), P63159 (Rn)

Inhibitors

3-AESA pK_d 8.8 [7]

methotrexate pK_d 7.6 [7]

Comment

HMGB1 is a nuclear non-histone protein that is important for the regulation of cell survival/death pathways and the innate immune response. Its secretion is upregulated in response to cellular damage or stress [7]. HMGB1 also has cytokine-like activity that modulates the response to infectious and sterile inflammation. The protein is an endogenous ligand for Toll-like receptors 2 and 4, and RAGE [4,6], and it can bind to RNA in addition to its DNA binding functions [3].

References

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1. Hock R, Furusawa T, Ueda T, Bustin M. (2007) HMG chromosomal proteins in development and disease. Trends Cell Biol, 17 (2): 72-9. [PMID:17169561]

2. Homma H, Tanaka H, Fujita K, Okazawa H. (2024) Necrosis Links Neurodegeneration and Neuroinflammation in Neurodegenerative Disease. Int J Mol Sci, 25 (7). [PMID:38612448]

3. Liao M, Cao J, Chen W, Wang M, Jin Z, Ye J, Ren Y, Wei Y, Xue Y, Chen D et al.. (2024) HMGB1 prefers to interact with structural RNAs and regulates rRNA methylation modification and translation in HeLa cells. BMC Genomics, 25 (1): 345. [PMID:38580917]

4. Mattke J, Darden CM, Lawrence MC, Kuncha J, Shah YA, Kane RR, Naziruddin B. (2024) Toll-like receptor 4 in pancreatic damage and immune infiltration in acute pancreatitis. Front Immunol, 15: 1362727. [PMID:38585277]

5. Mouse Gene Nomenclature Committee. High mobility group (HMG) chromosomal proteins nomenclature home page. Accessed on 15/04/2024. Modified on 15/04/2024. http://www.informatics.jax.org, http://www.informatics.jax.org/mgihome/nomen/hmg_family.shtml

6. Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. (2010) HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol, 28: 367-88. [PMID:20192808]

7. VanPatten S, Al-Abed Y. (2018) High Mobility Group Box-1 (HMGb1): Current Wisdom and Advancement as a Potential Drug Target. J Med Chem, 61 (12): 5093-5107. [PMID:29268019]

8. Zheng Y, Wang Y, Qi B, Lang Y, Zhang Z, Ma J, Lou M, Liang X, Chang Y, Zhao Q et al.. (2024) IL6/adiponectin/HMGB1 feedback loop mediates adipocyte and macrophage crosstalk and M2 polarization after myocardial infarction. Front Immunol, 15: 1368516. [PMID:38601146]

How to cite this family page

Database page citation:

High Mobility Group (HMG) proteins. Accessed on 31/03/2026. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1098.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Gibb AJ, Kelly E, Mathie AA, Peach CJ, Veale EL, Cidlowski JA, Davenport AP, Fabbro D, Spedding M, Striessnig J, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Southan C, Davies JA et al. (2025) The Concise Guide to PHARMACOLOGY 2025/26: Introduction and Other Protein Targets. Br J Pharmacol. 182: S1-S23.