Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 (JMJD6)

The protein contains 403 amino acids for an estimated molecular weight of 46462 Da.

 

Dioxygenase that can both act as a arginine demethylase and a lysyl-hydroxylase (PubMed:24498420, PubMed:17947579, PubMed:20684070, PubMed:21060799, PubMed:22189873). Acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/U2AF65 and LUC7L2. Regulates RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/U2AF65 (PubMed:19574390). Hydroxylates its own N-terminus, which is required for homooligomerization (PubMed:22189873). In addition to peptidyl-lysine 5-dioxygenase activity, may act as an RNA hydroxylase, as suggested by its ability to bind single strand RNA (PubMed:20679243, PubMed:29176719). Also acts as an arginine demethylase which preferentially demethylates asymmetric dimethylation (PubMed:17947579, PubMed:24498420, PubMed:24360279). Demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), including mono-, symmetric di- and asymmetric dimethylated forms, thereby playing a role in histone code (PubMed:17947579, PubMed:24360279). However, histone arginine demethylation may not constitute the primary activity in vivo (PubMed:17947579, PubMed:21060799, PubMed:22189873). In collaboration with BRD4, interacts with the positive transcription elongation factor b (P-TEFb) complex in its active form to regulate polymerase II promoter-proximal pause release for transcriptional activation of a large cohort of genes. On distal enhancers, so (updated: Feb. 13, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 83%
Model score: 100
No model available.

(right-click above to access to more options from the contextual menu)

The reference OMIM entry for this protein is 604914

Jumonji domain-containing protein 6; jmjd6
Phosphatidylserine receptor; psr

CLONING

The culmination of apoptosis in vivo is phagocytosis of cellular corpses. During apoptosis, the asymmetry of plasma membrane phospholipids is lost, which exposes phosphatidylserine externally. The phagocytosis of apoptotic cells can be inhibited stereospecifically by phosphatidylserine and its structural analogs, but not by other anionic phospholipids, suggesting that phosphatidylserine is specifically recognized. Fadok et al. (2000) used phage display to clone a gene that appeared to recognize phosphatidylserine on apoptotic cells. Fadok et al. (2000) showed that this gene, phosphatidylserine receptor or PSR, when transfected into B and T lymphocytes, enabled them to recognize and engulf apoptotic cells in a phosphatidylserine-specific manner. Flow cytometric analysis using a monoclonal antibody suggested that the protein is expressed on the surface of macrophages, fibroblasts, and epithelial cells; this antibody, like phosphatidylserine liposomes, inhibited the phagocytosis of apoptotic cells and, in macrophages, induced an antiinflammatory state. This candidate phosphatidylserine receptor is highly homologous to genes in Caenorhabditis elegans and Drosophila, suggesting that phosphatidylserine recognition on apoptotic cells during their removal by phagocytes is highly conserved throughout phylogeny. Nagase et al. (1998) cloned the phosphatidylserine receptor from a human brain cDNA library and designated it KIAA0585. They demonstrated that KIAA0585 was highly homologous to an uncharacterized open reading frame in C. elegans. Using RT-PCR, Nagase et al. (1998) found that expression was high in heart, skeletal muscle, and kidney, and moderate or low in brain, placenta, lung, liver, pancreas, spleen, thymus, prostate, testis, and ovary. A number of homologous sequences were present in human, mouse, Drosophila, and C. elegans EST databases. The predicted 427-amino acid protein has 1 predicted transmembrane domain and an area in the C terminus that contains a series of serines that represent potential O-glycosylation sites. The predicted molecular weight for this protein based on sequence analysis was 47 to 48 kD for human, mouse, and Drosophila gene products and 40 kD for that of the nematode. Western blot analysis suggested an apparent molecular weight of 70 kD; deglycosylation reduces the apparent size to approximately 50 kD, which is compatible with the predicted molecular weight of 47 kD.

GENE FUNCTION

Fadok et al. (2000) transiently transfected cells from 2 cell lines that are not capable of binding or phagocytosing apoptotic cells (the mouse class II-negative B cell line M12.C3 and human Jurkat T cells), with PSR DNA and demonstrated binding of specific antibody. About 25% of M12.C3 cells were able to bind antibody and apoptotic targets, and about 12.5% were able to engulf apoptotic cells. Stably transfected Jurkat T cells bound reliably to apoptotic cells only when PS receptor expression was increased with PMA. Chang et al. (2007) demonstrated that JMJD6 is a JmjC-containing iron- and 2-oxoglutarate-dependent dioxygenase that demethylates histone H3 (see 602810) at arginine-2 (H3R2) and histone H4 (see 602822) at arginine-3 (H4R3) in both biochemical and cell-based assays. The authors suggested that their findings may help explain the many developmental defects observed in the Jmjd6-null mice. Webby et al. (2009) discovered that the splicing factor U2 small nuclear ribonucleoprotein auxiliary factor 6 ... More on the omim web site

Subscribe to this protein entry history

Feb. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604914 was added.

Jan. 27, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed