JHDM1: Members of the JHDM1 group are found in organisms from budding yeast to human. In addition to the JmjC domain, the human, mouse and D. melanogaster JHDM1 orthologues contain leucine-rich repeats (LRRs), an F-box domain and a CXXC zinc-finger domain. Using a novel activity-based histone demethylase assay, we recently identified the JHDM1 family of histone demethylases, and showed that the JmjC domain can specifically mediate Fe(II) and αKG-dependent histone demethylation. Both human JHDM1 homologues (JHDM1A and JHDM1B) and their orthologue from budding yeast are H3K36 histone demethylases. Little is known about the biological function of JHDM1 proteins, although the C. elegans orthologue can suppress spontaneous mutations and the fission yeast orthologue functions to limit heterochromatic domains at the mating type locus. (1)

Reference
1. Klose RJ,Kallin EM,Zhang Y (2006)JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet., 7:715-727. PMID: 16983801.

    JHDM2: The JHDM2 family of proteins have orthologues from flies to humans; they possess JmjC and modified zinc finger domains. The mammalian JHDM2 family is comprised of four human proteins: hairless (HR), JHDM2A, JHDM2B, and JHDM2C. HR was originally identified in mice, and its mutation results in universal congenital alopecia. Mutation in its human homologue also causes hereditary alopecia. HR is expressed in the skin and the brain, where it probably functions as a corepressor of the thyroid hormone receptor. (1)

Reference
1. Klose RJ,Kallin EM,Zhang Y (2007)JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet., 7:715-727. PMID: 16983801.

    JHDM3_JMJD2: The JHDM3_JMJD2 group of proteins has orthologues from yeast to humans. In higher eukaryotes, proteins of this family contain JmjN, PHD and Tudor domains in addition to the JmjC domain. There are four JHDM3_JMJD2 genes (JHDM3A_JMJD2A, JMJD2B, JMJD2C and JMJD2D) in the human genome, each of which has orthologues in the mouse. JHDM3A_JMJD2A was originally identified as a transcriptional repressor associated with the NCoR corepressor complex, but has also been shown to physically interact with RB to repress E2F target genes. More recently, it was suggested that the tandem Tudor domain of JHDM3A_JMJD2A potentially contains a chromatin targeting module that directly binds methylated H3K4, H3K9 and H4K20. (1)

Reference
1. Klose RJ,Kallin EM,Zhang Y (2008)JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet., 7:715-727. PMID: 16983801.

    JmjC_only: The seventh group that we discuss contains several JmjC domain- containing proteins that, apart from the JmjC domain, contain no other recognizable protein domains. This group forms its own branch that is based on homology within the JmjC domain, and includes all of the JmjC-domain proteins that are known to localize to the cytoplasm (FIH, PLA2G4B and HSPBAP1). We propose that these proteins, of which only the MINA53/NO66 group (see below) has orthologues in yeast, might have diverged in higher eukaryotes to carry out functions that are independent of histone demethylation. (1)

Reference
1. Klose RJ,Kallin EM,Zhang Y (2012)JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet., 7:715-727. PMID: 16983801.

    UTX_UTY: The ubiquitously transcribed tetratricopeptide repeat (TPR) UTX_UTY group of proteins have orthologues from worms to humans, and contain a tetratricopeptide repeat in addition to the JmjC domain. This group also includes the JMJD3 proteins (which have been identified in humans and mice) that lack the TPR domain. The function of the UTX_UTY proteins is largely unknown, except for the observation that UTY contributes to male-specific antigens, which can lead to the sex-specific tissue-transplantation rejection response. The expression and function of the UTX/UTY/JMJD3 orthologues in lower eukaryotes remain uncharacterized. (1)

Reference
1. Klose RJ,Kallin EM,Zhang Y (2011)JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet., 7:715-727. PMID: 16983801.