| IED ID | IndEnz0002007519 |
| Enzyme Type ID | protease007519 |
| Protein Name |
Bifunctional peptidase and arginyl-hydroxylase JMJD5 EC 1.14.11.73 EC 3.4.-.- JmjC domain-containing protein 5 Jumonji C domain-containing protein 5 L-arginine 3R -hydroxylase KDM8 Lysine-specific demethylase 8 |
| Gene Name | Kdm8 Jmjd5 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MSEDTTEPLVGSSTLWKELRTLLPDKEEELKLDLGEKVDRSVAALLRQAVGLFYAGHWQGCLQASEAVLDYSWEKLNTGPWRDVDKEWRRVYSFGCLLKALCLCQAPQKATTVVEALRVCDMGLLMGAAILEDILLKVVAVLQTHQLPGKQPARGPHQDQPATKKAKCDASPAPDVMLERMVPRLRCPPLQYFKQHFLVPGRPVILEGVADHWPCMKKWSLQYIQEIAGCRTVPVEVGSRYTDEDWSQTLMTVDEFIQKFILSEAKDVGYLAQHQLFDQIPELKRDISIPDYCCLGNGEEEEITINAWFGPQGTISPLHQDPQQNFLVQVLGRKYIRLYSPQESEAVYPHETHILHNTSQVDVENPDLEKFPKFTEAPFLSCILSPGDTLFIPAKYWHYVRSLDLSFSVSFWWS |
| Enzyme Length | 414 |
| Uniprot Accession Number | Q9CXT6 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 236; /note="N(omega)-methyl-L-arginine residue"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 270; /note="2-oxoglutarate"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 273; /note="N(omega)-methyl-L-arginine residue"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 273; /note="Symmetrical N(omega),N'(omega)-dimethyl-L-arginine residue"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 316; /note="2-oxoglutarate"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 316; /note="N(omega)-methyl-L-arginine residue; via carbonyl oxygen"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 316; /note="Symmetrical N(omega),N'(omega)-dimethyl-L-arginine residue; via carbonyl oxygen"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 319; /note="2-oxoglutarate"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 325; /note="2-oxoglutarate"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 334; /note="2-oxoglutarate"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 398; /note="2-oxoglutarate"; /evidence="ECO:0000250|UniProtKB:Q8N371"; BINDING 412; /note="2-oxoglutarate"; /evidence="ECO:0000250|UniProtKB:Q8N371" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + L-arginyl-[protein] + O2 = (3R)-3-hydroxy-L-arginyl-[protein] + CO2 + succinate; Xref=Rhea:RHEA:56744, Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:14712, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:29965, ChEBI:CHEBI:30031, ChEBI:CHEBI:78294; EC=1.14.11.73; Evidence={ECO:0000250|UniProtKB:Q8N371}; |
| DNA Binding | |
| EC Number | 1.14.11.73; 3.4.-.- |
| Enzyme Function | FUNCTION: Bifunctional enzyme that acts both as an endopeptidase and 2-oxoglutarate-dependent monooxygenase. Endopeptidase that cleaves histones N-terminal tails at the carboxyl side of methylated arginine or lysine residues, to generate 'tailless nucleosomes', which may trigger transcription elongation. Preferentially recognizes and cleaves monomethylated and dimethylated arginine residues of histones H2, H3 and H4. After initial cleavage, continues to digest histones tails via its aminopeptidase activity. Upon DNA damage, cleaves the N-terminal tail of histone H3 at monomethylated lysine residues, preferably at monomethylated 'Lys-9' (H3K9me1). The histone variant H3F3A is the major target for cleavage. Additionnally, acts as Fe(2+) and 2-oxoglutarate-dependent monooxygenase, catalyzing (R)-stereospecific hydroxylation at C-3 of 'Arg-137' of RPS6 and 'Arg-141' of RCCD1, but the biological significance of this activity remains to be established. Regulates mitosis through different mechanisms: Plays a role in transcriptional repression of satellite repeats, possibly by regulating H3K36 methylation levels in centromeric regions together with RCCD1. Possibly together with RCCD1, is involved in proper mitotic spindle organization and chromosome segregation. Negatively regulates cell cycle repressor CDKN1A/p21, which controls G1/S phase transition. Required for G2/M phase cell cycle progression. Regulates expression of CCNA1/cyclin-A1, leading to cancer cell proliferation. Also, plays a role in regulating alpha-tubulin acetylation and cytoskeletal microtubule stability involved in epithelial to mesenchymal transition (By similarity). Regulates the circadian gene expression in the liver (PubMed:30500822). Represses the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer in a catalytically-independent manner (By similarity). Negatively regulates the protein stability and function of CRY1; required for AMPK-FBXL3-induced CRY1 degradation (PubMed:30500822). {ECO:0000250|UniProtKB:Q8N371, ECO:0000269|PubMed:30500822}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Binding site (12); Chain (1); Domain (1); Metal binding (3); Region (2) |
| Keywords | Aminopeptidase;Biological rhythms;Cell cycle;Chromatin regulator;Chromosome;Dioxygenase;Hydrolase;Iron;Metal-binding;Nucleus;Oxidoreductase;Protease;Reference proteome;Transcription;Transcription regulation |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8N371}. Chromosome {ECO:0000250|UniProtKB:Q8N371}. Note=Colocalizes with trimethylated 'Lys-9' of histone H3 (H3K9me3). {ECO:0000250|UniProtKB:Q8N371}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11217851; 12466851; 15618518; 18799693; 20412781; 21677750; 22241836; 22402282; 24194600; 24300334; 25849460; 26334721; 26710852; 27626377; 27626380; 28847961; 29217679; 34368113; |
| Motif | |
| Gene Encoded By | |
| Mass | 47,145 |
| Kinetics | |
| Metal Binding | METAL 319; /note=Iron; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00538; METAL 321; /note=Iron; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00538; METAL 398; /note=Iron; catalytic; /evidence=ECO:0000255|PROSITE-ProRule:PRU00538 |
| Rhea ID | RHEA:56744 |
| Cross Reference Brenda |