| IED ID | IndEnz0002013447 |
| Enzyme Type ID | protease013447 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase 2 EC 3.4.19.12 41 kDa ubiquitin-specific protease Deubiquitinating enzyme 2 Ubiquitin thioesterase 2 Ubiquitin-specific-processing protease 2 |
| Gene Name | USP2 UBP41 |
| 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 | MSQLSSTLKRYTESARYTDAHYAKSGYGAYTPSSYGANLAASLLEKEKLGFKPVPTSSFLTRPRTYGPSSLLDYDRGRPLLRPDITGGGKRAESQTRGTERPLGSGLSGGSGFPYGVTNNCLSYLPINAYDQGVTLTQKLDSQSDLARDFSSLRTSDSYRIDPRNLGRSPMLARTRKELCTLQGLYQTASCPEYLVDYLENYGRKGSASQVPSQAPPSRVPEIISPTYRPIGRYTLWETGKGQAPGPSRSSSPGRDGMNSKSAQGLAGLRNLGNTCFMNSILQCLSNTRELRDYCLQRLYMRDLHHGSNAHTALVEEFAKLIQTIWTSSPNDVVSPSEFKTQIQRYAPRFVGYNQQDAQEFLRFLLDGLHNEVNRVTLRPKSNPENLDHLPDDEKGRQMWRKYLEREDSRIGDLFVGQLKSSLTCTDCGYCSTVFDPFWDLSLPIAKRGYPEVTLMDCMRLFTKEDVLDGDEKPTCCRCRGRKRCIKKFSIQRFPKILVLHLKRFSESRIRTSKLTTFVNFPLRDLDLREFASENTNHAVYNLYAVSNHSGTTMGGHYTAYCRSPGTGEWHTFNDSSVTPMSSSQVRTSDAYLLFYELASPPSRM |
| Enzyme Length | 605 |
| Uniprot Accession Number | O75604 |
| Absorption | |
| Active Site | ACT_SITE 276; /note="Nucleophile"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093"; ACT_SITE 557; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, ECO:0000255|PROSITE-ProRule:PRU10093" |
| Activity Regulation | ACTIVITY REGULATION: Cleavage is inhibited by ubiquitin in a dosage-dependent manner. Cleavage is blocked by ubiquitin aldehyde. {ECO:0000269|PubMed:16905103}. |
| 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: Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1 (PubMed:17290220, PubMed:19917254, PubMed:19838211). Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities (By similarity). Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity (PubMed:17290220, PubMed:19838211). Has no deubiquitinase activity against p53/TP53 (PubMed:17290220). Prevents MDM2-mediated degradation of MDM4 (PubMed:17290220). Plays a role in the G1/S cell-cycle progression in normal and cancer cells (PubMed:19917254). Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (By similarity). Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability (By similarity). Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and ARNTL/BMAL1 (By similarity). Plays a role in the regulation of myogenic differentiation of embryonic muscle cells (By similarity). {ECO:0000250|UniProtKB:O88623, ECO:0000250|UniProtKB:Q5U349, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19838211, ECO:0000269|PubMed:19917254}.; FUNCTION: [Isoform 4]: Circadian clock output effector that regulates Ca(2+) absorption in the small intestine. Probably functions by regulating protein levels of the membrane scaffold protein NHERF4 in a rhythmic manner, and is therefore likely to control Ca(2+) membrane permeability mediated by the Ca(2+) channel TRPV6 in the intestine. {ECO:0000250|UniProtKB:O88623}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (4); Beta strand (18); Chain (1); Compositional bias (1); Domain (1); Helix (13); Metal binding (4); Mutagenesis (2); Natural variant (2); Region (4); Sequence conflict (5); Turn (3) |
| Keywords | 3D-structure;Alternative splicing;Biological rhythms;Cell cycle;Cytoplasm;Hydrolase;Membrane;Metal-binding;Myogenesis;Nucleus;Protease;Reference proteome;Thiol protease;Ubl conjugation pathway;Zinc |
| Interact With | Q9NYB9-2; P12814; P35609; Q08043; Q86U10; Q86V38; P56945; Q6PI77; Q8TD16-2; Q96CA5; A2RRN7; Q13137; Q9H257-2; Q96JN2-2; Q2TAC2; A6NC98; Q96MT8-3; Q8NHQ1; Q9BSW2; Q8N4Y2-3; Q8WTU0; O75140-2; Q9NRI5-2; Q8N9I9; Q9H596; Q8WWB3; Q5JST6; Q9NRA8; O00471; Q96B26; P57678; Q08379; Q9NYA3; A6NEM1; Q14451-3; Q4V328; Q9NSC5; Q9UJC3; Q96ED9-2; Q8IYA8; Q9UKT9; Q5TA45; Q96N16; O75564-2; Q674X7-2; Q9BVG8; Q9BVG8-5; P19012; Q7Z3Y8; Q15323; Q14525; O76011; Q92764; Q6A162; Q9UBR4-2; Q969G2; Q03252; Q9BRK4; Q00987; Q9UJV3-2; Q5VZ52; Q13084; Q5JR59; Q5JR59-3; Q15742; Q9GZM8; I6L9F6; P07196; O43482; Q96CV9; Q4G0R1; Q9NRD5; Q58EX7; Q8ND90; Q16633; Q9GZV8; Q6MZQ0; Q15276; Q8HWS3; Q59EK9-3; P60903; O14492-2; O60504; Q99932-2; A6NLX3; P51692; Q86VP1; Q8WW24; Q9UBB9; Q08117-2; Q03169; Q13077; Q12933; Q9Y4K3; P36406; P14373; Q86XT4; Q15654; Q8N6Y0; Q70EL1-9; Q9UK41-2; Q8N1B4; O96006; Q9NZV7; Q9UGI0; P05067; P54253; G5E9A7; Q01658; Q00403; Q9Y5Q9; P04792; O43464; P42858; Q8WXH2; O60333-2; D3DTS7; O60260-5; P60891; Q9Y3C5; Q7Z333; P37840; P00441; Q7Z699; Q13148; O76024 |
| Induction | INDUCTION: Down-regulated by cisplatin (at protein level). {ECO:0000269|PubMed:19838211}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O88623}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:O88623}. Note=Localizes in the spermatid head in late-elongating spermatids in the thin area between the outer acrosomal membrane and the plasma membrane. {ECO:0000250|UniProtKB:Q5U349}.; SUBCELLULAR LOCATION: [Isoform 4]: Nucleus {ECO:0000250|UniProtKB:Q5U349}. Membrane {ECO:0000250|UniProtKB:O88623}; Peripheral membrane protein {ECO:0000305}. Cytoplasm {ECO:0000250|UniProtKB:O88623}. Note=Predominantly expressed at membranes. {ECO:0000250|UniProtKB:O88623}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (8) |
| Cross Reference PDB | 2HD5; 2IBI; 3NHE; 3V6C; 3V6E; 5XU8; 5XVE; 6DGF; |
| Mapped Pubmed ID | 12566314; 12887920; 15050917; 16189514; 16260783; 16603398; 16953224; 17502873; 17553343; 18178551; 19373254; 19615732; 19910467; 21293491; 21478478; 21480224; 21826056; 21890637; 22179575; 22370483; 22435550; 22611252; 22659130; 22669941; 22710717; 22848449; 23264041; 23287719; 23313255; 23416128; 24071644; 24098568; 24445145; 25026213; 25070846; 25260751; 25416956; 25687182; 25888580; 26033248; 26250800; 27351221; 27434509; 27436899; 27479112; 27681596; 28536428; 29230097; 29449607; 29490279; 30763569; 30918246; 32327714; 33074477; 33582217; 34425107; 34489969; 9325273; |
| Motif | |
| Gene Encoded By | |
| Mass | 68,072 |
| Kinetics | |
| Metal Binding | METAL 425; /note=Zinc; /evidence=ECO:0000269|PubMed:16905103; METAL 428; /note=Zinc; /evidence=ECO:0000269|PubMed:16905103; METAL 476; /note=Zinc; /evidence=ECO:0000269|PubMed:16905103; METAL 479; /note=Zinc; /evidence=ECO:0000269|PubMed:16905103 |
| Rhea ID | |
| Cross Reference Brenda |