| IED ID | IndEnz0002007518 |
| Enzyme Type ID | protease007518 |
| 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 |
| Gene Name | KDM8 JMJD5 |
| Organism | Homo sapiens (Human) |
| 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 Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MAGDTHCPAEPLAREGTLWEALRALLPHSKEDLKLDLGEKVERSVVTLLQRATELFYEGRRDECLQSSEVILDYSWEKLNTGTWQDVDKDWRRVYAIGCLLKALCLCQAPEDANTVAAALRVCDMGLLMGAAILGDILLKVAAILQTHLPGKRPARGSLPEQPCTKKARADHGLIPDVKLEKTVPRLHRPSLQHFREQFLVPGRPVILKGVADHWPCMQKWSLEYIQEIAGCRTVPVEVGSRYTDEEWSQTLMTVNEFISKYIVNEPRDVGYLAQHQLFDQIPELKQDISIPDYCSLGDGEEEEITINAWFGPQGTISPLHQDPQQNFLVQVMGRKYIRLYSPQESGALYPHDTHLLHNTSQVDVENPDLEKFPKFAKAPFLSCILSPGEILFIPVKYWHYVRALDLSFSVSFWWS |
| Enzyme Length | 416 |
| Uniprot Accession Number | Q8N371 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 238; /note="N(omega)-methyl-L-arginine residue"; /evidence="ECO:0000269|PubMed:29459673"; BINDING 272; /note="2-oxoglutarate"; /evidence="ECO:0000269|PubMed:22851697, ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, ECO:0000305|PubMed:24100311, ECO:0007744|PDB:3UYJ, ECO:0007744|PDB:4GJZ, ECO:0007744|PDB:4QU1, ECO:0007744|PDB:5FBJ"; BINDING 275; /note="N(omega)-methyl-L-arginine residue"; /evidence="ECO:0000269|PubMed:29459673"; BINDING 275; /note="Symmetrical N(omega),N'(omega)-dimethyl-L-arginine residue"; /evidence="ECO:0000269|PubMed:29459673"; BINDING 318; /note="2-oxoglutarate"; /evidence="ECO:0000269|PubMed:22851697, ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, ECO:0000305|PubMed:24100311, ECO:0007744|PDB:3UYJ, ECO:0007744|PDB:4GJZ, ECO:0007744|PDB:4QU1, ECO:0007744|PDB:5FBJ"; BINDING 318; /note="N(omega)-methyl-L-arginine residue; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:29459673"; BINDING 318; /note="Symmetrical N(omega),N'(omega)-dimethyl-L-arginine residue; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:29459673"; BINDING 321; /note="2-oxoglutarate"; /evidence="ECO:0000269|PubMed:29563586"; BINDING 327; /note="2-oxoglutarate"; /evidence="ECO:0000269|PubMed:22851697, ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, ECO:0000305|PubMed:24100311, ECO:0007744|PDB:3UYJ, ECO:0007744|PDB:4GJZ, ECO:0007744|PDB:4QU1, ECO:0007744|PDB:5FBJ"; BINDING 336; /note="2-oxoglutarate"; /evidence="ECO:0000269|PubMed:22851697, ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, ECO:0000305|PubMed:24100311, ECO:0007744|PDB:3UYJ, ECO:0007744|PDB:4GJZ, ECO:0007744|PDB:4QU1, ECO:0007744|PDB:5FBJ"; BINDING 400; /note="2-oxoglutarate"; /evidence="ECO:0000269|PubMed:29563586"; BINDING 414; /note="2-oxoglutarate"; /evidence="ECO:0000269|PubMed:22851697, ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, ECO:0007744|PDB:3UYJ, ECO:0007744|PDB:4GJZ" |
| 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:0000269|PubMed:29563586}; |
| 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 (PubMed:28847961, PubMed:29459673, PubMed:28982940, PubMed:29563586). 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 (PubMed:28847961, PubMed:29459673, PubMed:28982940). 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 (PubMed:28847961, PubMed:29459673). 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 (PubMed:28982940). 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 (PubMed:29563586). 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 (PubMed:24981860). Negatively regulates cell cycle repressor CDKN1A/p21, which controls G1/S phase transition (PubMed:24740926). Required for G2/M phase cell cycle progression. Regulates expression of CCNA1/cyclin-A1, leading to cancer cell proliferation (PubMed:20457893). Also, plays a role in regulating alpha-tubulin acetylation and cytoskeletal microtubule stability involved in epithelial to mesenchymal transition (PubMed:28455245). Regulates the circadian gene expression in the liver (By similarity). Represses the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer in a catalytically-independent manner (PubMed:30500822). Negatively regulates the protein stability and function of CRY1; required for AMPK-FBXL3-induced CRY1 degradation (PubMed:30500822). {ECO:0000250|UniProtKB:Q9CXT6, ECO:0000269|PubMed:20457893, ECO:0000269|PubMed:24740926, ECO:0000269|PubMed:24981860, ECO:0000269|PubMed:28455245, ECO:0000269|PubMed:28847961, ECO:0000269|PubMed:28982940, ECO:0000269|PubMed:29459673, ECO:0000269|PubMed:29563586, ECO:0000269|PubMed:30500822}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Beta strand (16); Binding site (12); Chain (1); Domain (1); Helix (11); Metal binding (3); Mutagenesis (15); Natural variant (1); Region (1); Sequence conflict (1); Turn (3) |
| Keywords | 3D-structure;Alternative splicing;Aminopeptidase;Biological rhythms;Cell cycle;Chromatin regulator;Chromosome;Dioxygenase;Hydrolase;Iron;Metal-binding;Nucleus;Oxidoreductase;Protease;Reference proteome;Transcription;Transcription regulation |
| Interact With | A6NED2; Q96D03; Q8IY31-3; Q9ULR0; Q6FHY5; Q8TB37 |
| Induction | INDUCTION: Up-regulated upon starvation, DNA replication stress, UV treatment and by camptothecin and etoposide treatment. {ECO:0000269|PubMed:28982940}. |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20457893, ECO:0000269|PubMed:28982940}. Chromosome {ECO:0000269|PubMed:24981860}. Note=Colocalizes with trimethylated 'Lys-9' of histone H3 (H3K9me3). {ECO:0000269|PubMed:24981860}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (20) |
| Cross Reference PDB | 3UYJ; 4AAP; 4GAZ; 4GJY; 4GJZ; 4QU1; 5FBJ; 6AVS; 6AX3; 6F4M; 6F4N; 6F4O; 6F4P; 6F4Q; 6F4R; 6F4S; 6F4T; 6I9L; 6I9M; 6I9N; |
| Mapped Pubmed ID | 16189514; 16858412; 21115819; 22375008; 23948433; 24344305; 26025680; 26261525; 26710852; 26760772; 26792738; 27715397; 30072740; 30551455; 32747552; |
| Motif | |
| Gene Encoded By | |
| Mass | 47,270 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=60.4 uM for ARG-137 of RPS6 {ECO:0000269|PubMed:29563586}; Note=KM>300 uM for ARG-141 of RCCD1. {ECO:0000269|PubMed:29563586}; |
| Metal Binding | METAL 321; /note="Iron; catalytic"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00538, ECO:0000305|PubMed:22851697, ECO:0000305|PubMed:24100311, ECO:0007744|PDB:4GJY, ECO:0007744|PDB:4GJZ"; METAL 323; /note="Iron; catalytic"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00538, ECO:0000305|PubMed:22851697, ECO:0000305|PubMed:24100311, ECO:0007744|PDB:4GJY, ECO:0007744|PDB:4GJZ"; METAL 400; /note="Iron; catalytic"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00538, ECO:0000305|PubMed:22851697, ECO:0000305|PubMed:24100311, ECO:0007744|PDB:4GJY, ECO:0007744|PDB:4GJZ" |
| Rhea ID | RHEA:56744 |
| Cross Reference Brenda | 1.14.11.73; |