title: The oxygenase Jmjd6--a case study in conflicting assignments.
abstract: The Jumonji domain-containing protein 6 (Jmjd6) is a member of the superfamily of non-haem iron(II) and 2-oxoglutarate (2OG)-dependent oxygenases; it plays an important developmental role in higher animals. Jmjd6 was initially assigned a role as the phosphatidylserine receptor responsible for engulfment of apoptotic cells but this now seems unlikely. Jmjd6 has been shown to be a nuclear localized protein with a JmjC domain comprising a distorted double-stranded β-helical structure characteristic of the 2OG-dependent oxygenases. Jmjd6 was subsequently assigned a role in catalysing N-methyl-arginine residue demethylation on the N-terminus of the human histones H3 and H4; however, this function is also subject to conflicting reports. Jmjd6 does catalyse 2OG-dependent C-5 hydroxylation of lysine residues in mRNA splicing-regulatory proteins and histones; there is also accumulating evidence that Jmjd6 plays a role in splicing (potentially in an iron- and oxygen-dependent manner) as well as in other processes regulating gene expression, including transcriptional pause release. Moreover, a link with tumour progression has been suggested. In the present review we look at biochemical, structural and cellular work on Jmjd6, highlighting areas of controversy and consensus.
authors.affiliation: *Department of Biology II, Ludwig Maximillians University, Munich, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Böttger
authors.affiliation: †Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK.
authors.forename: Md Saiful
authors.initials: MS
authors.lastname: Islam
authors.affiliation: †Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK.
authors.forename: Rasheduzzaman
authors.initials: R
authors.lastname: Chowdhury
authors.affiliation: †Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
authors.affiliation: ‡Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wolf
mesh_terms: D000595:Amino Acid Sequence; D002468:Cell Physiological Phenomena; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases