Cellular and Molecular Life Sciences

, Volume 74, Issue 13, pp 2333–2344 | Cite as

MLL5 (KMT2E): structure, function, and clinical relevance

  • Xiaoming Zhang
  • Wisna Novera
  • Yan Zhang
  • Lih-Wen Deng


The mixed lineage leukemia (MLL) family of genes, also known as the lysine N-methyltransferase 2 (KMT2) family, are homologous to the evolutionarily conserved trithorax group that plays critical roles in the regulation of homeotic gene (HOX) expression and embryonic development. MLL5, assigned as KMT2E on the basis of its SET domain homology, was initially categorized under MLL (KMT2) family together with other six SET methyltransferase domain proteins (KMT2A–2D and 2F–2G). However, emerging evidence suggests that MLL5 is distinct from the other MLL (KMT2) family members, and the protein it encodes appears to lack intrinsic histone methyltransferase (HMT) activity towards histone substrates. MLL5 has been reported to play key roles in diverse biological processes, including cell cycle progression, genomic stability maintenance, adult hematopoiesis, and spermatogenesis. Recent studies of MLL5 variants and isoforms and putative MLL5 homologs in other species have enriched our understanding of the role of MLL5 in gene expression regulation, although the mechanism of action and physiological function of MLL5 remains poorly understood. In this review, we summarize recent research characterizing the structural features and biological roles of MLL5, and we highlight the potential implications of MLL5 dysfunction in human disease.


Histone methylation PHD finger Cell division Hematopoietic stem cell differentiation Leukemia Cancer 



This work is supported by the Ministry of Education Academic Research Fund Tier 1 Grant (R-183-000-337-112) and Tier 2 Grant (R-183-000-354-112), Singapore. We thank K. McLaughlin of Insight Editing London for critical review of the manuscript. We also thank Z.W. Lee and W. Zhao for helpful suggestions regarding manuscript structure.

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.


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Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  1. 1.Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health SystemNational University of SingaporeSingaporeSingapore
  2. 2.Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of ShanghaiChinese Academy of SciencesShanghaiChina
  3. 3.National University Cancer InstituteNational University Health SystemSingaporeSingapore

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