title: MLL5 (KMT2E): structure, function, and clinical relevance.
abstract: 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.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 8 Medical Drive, MD 7 #04-06, Singapore, 117597, Singapore.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 8 Medical Drive, MD 7 #04-06, Singapore, 117597, Singapore.
authors.forename: Wisna
authors.initials: W
authors.lastname: Novera
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, 8 Medical Drive, MD 7 #04-06, Singapore, 117597, Singapore. bchdlw@nus.edu.sg.|National University Cancer Institute, National University Health System, Singapore, Singapore. bchdlw@nus.edu.sg.
authors.forename: Lih-Wen
authors.identifier: 0000-0002-4985-7844
authors.initials: LW
authors.lastname: Deng
mesh_terms: D000818:Animals; D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004194:Disease; D042822:Genomic Instability; D006801:Humans; D009154:Mutation / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D020033:Protein Isoforms
keywords: Cancer; Cell division; Hematopoietic stem cell differentiation; Histone methylation; Leukemia; PHD finger