| IED ID | IndEnz0002009269 |
| Enzyme Type ID | protease009269 |
| Protein Name |
OTU domain-containing protein 4 EC 3.4.19.12 HIV-1-induced protein HIN-1 |
| Gene Name | OTUD4 HIN-1 KIAA1046 |
| 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 | MEAAVGVPDGGDQGGAGPREDATPMDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQVEISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYPIKYKESSAMCQSLLYELLYEKVFKTDVSKIVMELDTLEVADEDNSEISDSEDDSCKSKTAAAAADVNGFKPLSGNEQLKNNGNSTSLPLSRKVLKSLNPAVYRNVEYEIWLKSKQAQQKRDYSIAAGLQYEVGDKCQVRLDHNGKFLNADVQGIHSENGPVLVEELGKKHTSKNLKAPPPESWNTVSGKKMKKPSTSGQNFHSDVDYRGPKNPSKPIKAPSALPPRLQHPSGVRQHAFSSHSSGSQSQKFSSEHKNLSRTPSQIIRKPDRERVEDFDHTSRESNYFGLSPEERREKQAIEESRLLYEIQNRDEQAFPALSSSSVNQSASQSSNPCVQRKSSHVGDRKGSRRRMDTEERKDKDSIHGHSQLDKRPEPSTLENITDDKYATVSSPSKSKKLECPSPAEQKPAEHVSLSNPAPLLVSPEVHLTPAVPSLPATVPAWPSEPTTFGPTGVPAPIPVLSVTQTLTTGPDSAVSQAHLTPSPVPVSIQAVNQPLMPLPQTLSLYQDPLYPGFPCNEKGDRAIVPPYSLCQTGEDLPKDKNILRFFFNLGVKAYSCPMWAPHSYLYPLHQAYLAACRMYPKVPVPVYPHNPWFQEAPAAQNESDCTCTDAHFPMQTEASVNGQMPQPEIGPPTFSSPLVIPPSQVSESHGQLSYQADLESETPGQLLHADYEESLSGKNMFPQPSFGPNPFLGPVPIAPPFFPHVWYGYPFQGFIENPVMRQNIVLPSDEKGELDLSLENLDLSKDCGSVSTVDEFPEARGEHVHSLPEASVSSKPDEGRTEQSSQTRKADTALASIPPVAEGKAHPPTQILNRERETVPVELEPKRTIQSLKEKTEKVKDPKTAADVVSPGANSVDSRVQRPKEESSEDENEVSNILRSGRSKQFYNQTYGSRKYKSDWGYSGRGGYQHVRSEESWKGQPSRSRDEGYQYHRNVRGRPFRGDRRRSGMGDGHRGQHT |
| Enzyme Length | 1114 |
| Uniprot Accession Number | Q01804 |
| Absorption | |
| Active Site | ACT_SITE 42; /evidence="ECO:0000250|UniProtKB:Q96FW1"; ACT_SITE 45; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:25944111, 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:0000269|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:0000269|PubMed:23827681, ECO:0000269|PubMed:25944111, ECO:0000269|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 (PubMed:23827681, PubMed:25944111, PubMed:29395066). 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 (PubMed:25944111). {ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:25944111, ECO:0000269|PubMed:29395066}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (3); Chain (1); Compositional bias (10); Domain (1); Erroneous initiation (1); Modified residue (22); Mutagenesis (7); Natural variant (3); Region (7); Sequence caution (2); Sequence conflict (2) |
| Keywords | Acetylation;Alternative splicing;Cytoplasm;Direct protein sequencing;Hydrolase;Immunity;Innate immunity;Nucleus;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation pathway |
| Interact With | Q96B26; Q04864; P42224; P15884; P11473-2; Q8N720 |
| Induction | INDUCTION: By HIV-1 insertion. {ECO:0000269|PubMed:1475186}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25944111}. Nucleus {ECO:0000269|PubMed:25944111}. Note=Primarily cytoplasmic. {ECO:0000269|PubMed:25944111}. |
| Modified Residue | MOD_RES 1; /note="N-acetylmethionine"; /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"; MOD_RES 120; /note="Phosphotyrosine"; /evidence="ECO:0000269|PubMed:29395066"; MOD_RES 126; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:29395066"; MOD_RES 128; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:29395066"; MOD_RES 131; /note="Phosphothreonine"; /evidence="ECO:0000269|PubMed:29395066"; MOD_RES 166; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:29395066"; MOD_RES 199; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:29395066"; MOD_RES 202; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:29395066"; MOD_RES 204; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:29395066"; MOD_RES 341; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 439; /note="Phosphotyrosine"; /evidence="ECO:0000250|UniProtKB:B2RRE7"; MOD_RES 443; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 460; /note="Phosphotyrosine"; /evidence="ECO:0007744|PubMed:15144186"; MOD_RES 546; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 893; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 900; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231"; MOD_RES 1006; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692"; MOD_RES 1011; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:B2RRE7"; MOD_RES 1014; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 1023; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 1024; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 1049; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163" |
| Post Translational Modification | PTM: Phosphorylated on Ser-202 and Ser-204 likely by CSNK2A1-CSNK2A2 serine/threonine-protein kinase complex. Activates 'Lys-63'-specific deubiquitinase activity. {ECO:0000269|PubMed:29395066}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 17353931; 17461779; 19167051; 19615732; 20711500; 21150319; 22575643; 25416956; 26496610; |
| Motif | |
| Gene Encoded By | |
| Mass | 124,045 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |