| IED ID | IndEnz0002012760 |
| Enzyme Type ID | protease012760 |
| Protein Name |
OTU domain-containing protein 4 EC 3.4.19.12 |
| Gene Name | Otud4 Kiaa1046 |
| 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 | MEAAVGAPDGVDQGGVGPLEDETPMDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIRYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQVEISALSLMYRKDFVIYQEPNVSPSHVTENNFPEKVLLCFSNGNHYDIVYPITYKDSSAMCQSLLYELLYEKVFKTDVSKIMMGLEASEVAEESNSEISDSEDDSCKSKSTAATDVNGFKPSGSENPKNNGNSADLPLSRKVLKSLNPAVYRNVEYEIWLKSKQAQQKRDYSIAAGLQYEVGDKCHQVRLDHNGKLSNADIHGVHSENGLVLSEELGKKHTPKNLKPPPPESWNTVSGKKMKKPNSGQNFHSDTDYRGPKNLNKPIKAPSALPPRLQHPSSGVRQHAFSSHSTGSQSQKSSSEHKNLSRMPSQITRKPDRERAEDFDHVSRESYYFGLSPEERREKQAIEESRLLYEIQNRDEQAFPALSSSSVSQSPSQNSNACVPRKSSHARDRKGSMRRADAEERKDKDSLRGHTHVDKKPEPSTLEISDDKCTRVSSPSKSKKECPSPVEQKPAEHIPLSNPAPLLVSPEVHLTPAVPSLPATVPAWPSEPTTFGPTGVPAQIPILSVTQTTGPDAAVSQAHLTPSPVPVSIQAVNQPLMPLPQTMSLYQDPLYPGFPCSEKGDRAIAPPYSLCQTGEDLPKDKNILRFFFNLGVKAYSCPMWAPHSYLYPLHQAYMAACRMYPKVPVPVYPQNTWFQEAPPAQSESDCPCTDAHYSLHPEASVNGQMPQAEMGPPAFASPLVIPPSQVSEGHGQLSYQPELESENPGQLLHAEYEESLSGKNMYPQQSFGPNPFLGPVPIAPPFFPHVWYGYPFQGFVENPVMRQNIVLPPDDKGELDLPLENLDLSKECDSVSAVDEFPDARVEGAHSLSAASVSSKHEGRVEQSSQTRKADIDLASGSSAVEGKGHPPTQILNREREPGSAEPEPKRTIQSLKEKPEKVKDPKTAADVVSPGANSVDRLQRPKEESSEDENEVSNILRSGRSKQFYNQTYGSRKYKSDWGSSGRGGYQHVRGEESWKGQPNRSRDEGYQYHRHVRGRPYRGDRRRSGMGDGHRGQHT |
| Enzyme Length | 1107 |
| Uniprot Accession Number | B2RRE7 |
| Absorption | |
| Active Site | ACT_SITE 42; /evidence=ECO:0000250|UniProtKB:Q96FW1; ACT_SITE 45; /note=Nucleophile; /evidence=ECO:0000269|PubMed:29395066; ACT_SITE 148; /evidence=ECO:0000250|UniProtKB:Q5VVQ6 |
| Activity Regulation | ACTIVITY REGULATION: Phosphorylation on Ser-202 and Ser-204 induces 'Lys-63'-specific deubiquitinase activity. {ECO:0000305|PubMed:29395066}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000305|PubMed:29395066}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein. May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (By similarity). {ECO:0000250|UniProtKB:Q01804, ECO:0000269|PubMed:29395066}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Compositional bias (10); Domain (1); Modified residue (20); Mutagenesis (1); Region (7); Sequence conflict (1) |
| Keywords | Acetylation;Cytoplasm;Hydrolase;Immunity;Innate immunity;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation pathway |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q01804}. Nucleus {ECO:0000250|UniProtKB:Q01804}. Note=Primarily cytoplasmic. {ECO:0000250|UniProtKB:Q01804}. |
| Modified Residue | MOD_RES 1; /note="N-acetylmethionine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 120; /note="Phosphotyrosine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 126; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 128; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 131; /note="Phosphothreonine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 166; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 199; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 202; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:29395066"; MOD_RES 204; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 340; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 438; /note="Phosphotyrosine"; /evidence="ECO:0007744|PubMed:17947660"; MOD_RES 442; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 459; /note="Phosphotyrosine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 544; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 895; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q01804"; MOD_RES 1000; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:21183079"; MOD_RES 1005; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:21183079"; MOD_RES 1016; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"; MOD_RES 1017; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"; MOD_RES 1042; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q01804" |
| Post Translational Modification | PTM: Phosphorylation at Ser-202 and Ser-204 activates 'Lys-63'-specific deubiquitinase activity. Induced upon stimulation with IL1B. {ECO:0000305|PubMed:29395066}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10725249; 11217851; 12466851; 14610273; 22878500; 24194600; 30410068; 31964525; |
| Motif | |
| Gene Encoded By | |
| Mass | 123,055 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |