| IED ID | IndEnz0002012530 |
| Enzyme Type ID | protease012530 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase 6 EC 3.4.19.12 Deubiquitinating enzyme 6 Proto-oncogene TRE-2 Ubiquitin thioesterase 6 Ubiquitin-specific-processing protease 6 |
| Gene Name | USP6 HRP1 TRE2 |
| 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 | MDMVENADSLQAQERKDILMKYDKGHRAGLPEDKGPEPVGINSSIDRFGILHETELPPVTAREAKKIRREMTRTSKWMEMLGEWETYKHSSKLIDRVYKGIPMNIRGPVWSVLLNIQEIKLKNPGRYQIMKERGKRSSEHIHHIDLDVRTTLRNHVFFRDRYGAKQRELFYILLAYSEYNPEVGYCRDLSHITALFLLYLPEEDAFWALVQLLASERHSLPGFHSPNGGTVQGLQDQQEHVVPKSQPKTMWHQDKEGLCGQCASLGCLLRNLIDGISLGLTLRLWDVYLVEGEQVLMPITSIALKVQQKRLMKTSRCGLWARLRNQFFDTWAMNDDTVLKHLRASTKKLTRKQGDLPPPAKREQGSLAPRPVPASRGGKTLCKGYRQAPPGPPAQFQRPICSASPPWASRFSTPCPGGAVREDTYPVGTQGVPSLALAQGGPQGSWRFLEWKSMPRLPTDLDIGGPWFPHYDFEWSCWVRAISQEDQLATCWQAEHCGEVHNKDMSWPEEMSFTANSSKIDRQKVPTEKGATGLSNLGNTCFMNSSIQCVSNTQPLTQYFISGRHLYELNRTNPIGMKGHMAKCYGDLVQELWSGTQKSVAPLKLRRTIAKYAPKFDGFQQQDSQELLAFLLDGLHEDLNRVHEKPYVELKDSDGRPDWEVAAEAWDNHLRRNRSIIVDLFHGQLRSQVKCKTCGHISVRFDPFNFLSLPLPMDSYMDLEITVIKLDGTTPVRYGLRLNMDEKYTGLKKQLRDLCGLNSEQILLAEVHDSNIKNFPQDNQKVQLSVSGFLCAFEIPVPSSPISASSPTQIDFSSSPSTNGMFTLTTNGDLPKPIFIPNGMPNTVVPCGTEKNFTNGMVNGHMPSLPDSPFTGYIIAVHRKMMRTELYFLSPQENRPSLFGMPLIVPCTVHTRKKDLYDAVWIQVSWLARPLPPQEASIHAQDRDNCMGYQYPFTLRVVQKDGNSCAWCPQYRFCRGCKIDCGEDRAFIGNAYIAVDWHPTALHLRYQTSQERVVDKHESVEQSRRAQAEPINLDSCLRAFTSEEELGESEMYYCSKCKTHCLATKKLDLWRLPPFLIIHLKRFQFVNDQWIKSQKIVRFLRESFDPSAFLVPRDPALCQHKPLTPQGDELSKPRILAREVKKVDAQSSAGKEDMLLSKSPSSLSANISSSPKGSPSSSRKSGTSCPSSKNSSPNSSPRTLGRSKGRLRLPQIGSKNKPSSSKKNLDASKENGAGQICELADALSRGHMRGGSQPELVTPQDHEVALANGFLYEHEACGNGCGDGYSNGQLGNHSEEDSTDDQREDTHIKPIYNLYAISCHSGILSGGHYITYAKNPNCKWYCYNDSSCEELHPDEIDTDSAYILFYEQQGIDYAQFLPKIDGKKMADTSSTDEDSESDYEKYSMLQ |
| Enzyme Length | 1406 |
| Uniprot Accession Number | P35125 |
| Absorption | |
| Active Site | ACT_SITE 541; /note="Nucleophile"; ACT_SITE 1328; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093" |
| Activity Regulation | |
| 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; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyzes its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity. Promotes plasma membrane localization of ARF6 and selectively regulates ARF6-dependent endocytic protein trafficking. Is able to initiate tumorigenesis by inducing the production of matrix metalloproteinases following NF-kappa-B activation. {ECO:0000269|PubMed:15509780, ECO:0000269|PubMed:16127172, ECO:0000269|PubMed:20418905}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (4); Chain (1); Compositional bias (4); Domain (2); Mutagenesis (3); Natural variant (3); Region (3); Sequence conflict (1) |
| Keywords | Alternative splicing;Calmodulin-binding;Cell membrane;Chromosomal rearrangement;Cytoplasm;Endosome;Hydrolase;Membrane;Protease;Proto-oncogene;Reference proteome;Thiol protease;Ubl conjugation;Ubl conjugation pathway |
| Interact With | Q8N8A2; P10916 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane. Cytoplasm. Endosome. Note=Localizes to the plasma membrane and to filamentous structures within the cell corresponding to ARF6 regulated tubular endosomes. Activation of RAC1 and CDC42 can direct the relocalization of USP6 to the plasma membrane in a manner that depends on the integrity of the actin cytoskeleton. |
| Modified Residue | |
| Post Translational Modification | PTM: Monubiquitinated; ubiquitination is calmodulin and calcium dependent. {ECO:0000269|PubMed:16127172}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 15509545; 16099424; 16555005; 16713569; 17701273; 18265974; 19060904; 19615732; 22081069; 22188517; 23748914; 23769422; 24742829; 25179595; 27113271; 27125357; 27162353; 27271298; 27440725; 28752842; 29061731; 29617048; 29980413; 30131449; 30297112; 30758758; 30767316; 30946936; 31827231; 31841517; 32011035; 32157177; 32583473; 32635781; 32661296; 33404853; 33558334; 33558945; 34089379; 34592198; |
| Motif | |
| Gene Encoded By | |
| Mass | 158,658 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |