| IED ID | IndEnz0010001918 |
| Enzyme Type ID | esterase001918 |
| Protein Name |
Ubiquitin carboxyl-terminal hydrolase isozyme L1 UCH-L1 EC 3.4.19.12 Neuron cytoplasmic protein 9.5 PGP 9.5 PGP9.5 Ubiquitin thioesterase L1 |
| Gene Name | UCHL1 |
| 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 | MQLKPMEINPEMLNKVLSRLGVAGQWRFVDVLGLEEESLGSVPAPACALLLLFPLTAQHENFRKKQIEELKGQEVSPKVYFMKQTIGNSCGTIGLIHAVANNQDKLGFEDGSVLKQFLSETEKMSPEDRAKCFEKNEAIQAAHDAVAQEGQCRVDDKVNFHFILFNNVDGHLYELDGRMPFPVNHGASSEDTLLKDAAKVCREFTEREQGEVRFSAVALCKAA |
| Enzyme Length | 223 |
| Uniprot Accession Number | P09936 |
| Absorption | |
| Active Site | ACT_SITE 90; /note=Nucleophile; /evidence=ECO:0000269|PubMed:20439756; ACT_SITE 161; /note=Proton donor; /evidence=ECO:0000269|PubMed:20439756 |
| 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; Evidence={ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:16475834, ECO:0000269|PubMed:20439756, ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}; |
| DNA Binding | |
| EC Number | 3.4.19.12 |
| Enzyme Function | FUNCTION: Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins (Probable). This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin (PubMed:9774100, PubMed:8639624, PubMed:12408865, PubMed:23359680). Also binds to free monoubiquitin and may prevent its degradation in lysosomes (By similarity). The homodimer may have ATP-independent ubiquitin ligase activity (PubMed:12408865). {ECO:0000250|UniProtKB:Q9R0P9, ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100, ECO:0000305|PubMed:12408865, ECO:0000305|PubMed:23359680, ECO:0000305|PubMed:8639624, ECO:0000305|PubMed:9774100}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Beta strand (9); Chain (1); Erroneous initiation (1); Helix (10); Lipidation (1); Modified residue (1); Mutagenesis (7); Natural variant (5); Propeptide (1); Region (2); Site (7); Turn (3) |
| Keywords | 3D-structure;Cytoplasm;Direct protein sequencing;Disease variant;Endoplasmic reticulum;Glycoprotein;Hereditary spastic paraplegia;Hydrolase;Lipoprotein;Membrane;Neurodegeneration;Oxidation;Parkinson disease;Parkinsonism;Phosphoprotein;Prenylation;Protease;Reference proteome;Thiol protease;Ubl conjugation pathway |
| Interact With | P63010-2; P05067; P05067-2; Q8N6T3-3; P18847; Q9H1Y0; O15392; Q8WUW1; P83916; P11802; Q00535; Q9UNS2; Q92905; P00533; O60739; Q8TC29; Q9UI08-2; Q8WVV9-3; Q14164; Q6DN90-2; Q96JM7-2; P13473-2; Q9BYZ2; O95777; A4FUJ8; Q15843; O15381-5; Q9BR81; Q13113; P62826; Q8TAI7; Q9ULX5; Q15554-4; Q9NYB0; P04637; Q9Y4K3; P19474; Q9BSL1; Q7KZS0; P61086; Q9UK80; Q86WB0-2 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261853}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:19261853}; Lipid-anchor {ECO:0000269|PubMed:19261853}. Note=About 30% of total UCHL1 is associated with membranes in brain. |
| Modified Residue | MOD_RES 125; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q00981 |
| Post Translational Modification | PTM: O-glycosylated. {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (7); NMR spectroscopy (1) |
| Cross Reference PDB | 2ETL; 2LEN; 3IFW; 3IRT; 3KVF; 3KW5; 4DM9; 4JKJ; |
| Mapped Pubmed ID | 11502942; 11535241; 11716150; 12123845; 12160938; 12210873; 12539205; 12775255; 12784265; 15194490; 15214825; 15221445; 15228595; 15716245; 15882803; 16007636; 16049941; 16169070; 16177983; 16316632; 16369839; 16371654; 16380264; 16402389; 16626667; 16642472; 16644676; 16698101; 16888648; 16941465; 17108109; 17144664; 17200335; 17287139; 17353931; 17599367; 17690318; 17925890; 17929277; 17994469; 18093156; 18250096; 18494032; 18499164; 18512240; 18543214; 18550537; 18638528; 18666234; 18820707; 18841579; 18949367; 18950315; 19017757; 19035297; 19141079; 19224617; 19329225; 19343046; 19477270; 19488775; 19536331; 19615732; 19683447; 19707515; 19859801; 19864305; 19945429; 19950834; 20029029; 20051117; 20104524; 20147297; 20160478; 20231490; 20302621; 20302855; 20381070; 20395212; 20524204; 20574456; 20608941; 20646535; 20713032; 20861575; 20949132; 21044950; 21251915; 21309726; 21315600; 21345711; 21426768; 21428722; 21504384; 21565611; 21626562; 21693148; 21702960; 21706495; 21878121; 21999842; 22001920; 22022780; 22028813; 22038515; 22076440; 22246902; 22279545; 22503729; 22617491; 22660851; 22688354; 22726800; 22839974; 22849656; 22883340; 22920679; 22931063; 22932395; 23061666; 23158209; 23291960; 23315218; 23392373; 23484054; 23490535; 23499448; 23543736; 23555160; 23603559; 23664488; 23686552; 23959334; 23996067; 24080464; 24086249; 24090154; 24309322; 24314660; 24702261; 24832624; 24908181; 24950120; 24959670; 2530630; 25354657; 25370916; 25403879; 25466238; 25578779; 25596590; 25615526; 25638021; 25640309; 25665578; 25687137; 25915537; 25973863; 26018507; 26040028; 26232084; 26264933; 26293643; 26314856; 26513019; 26547005; 26550574; 26702068; 26722437; 26752685; 26810533; 26823707; 26881020; 26899237; 27018834; 27215701; 27319802; 27840994; 27914685; 28002735; 28193576; 28300150; 28392346; 28472177; 28636190; 28651886; 28667290; 29126443; 29128359; 29150024; 29307588; 29339092; 29359783; 29401475; 29462615; 29489474; 29627846; 29765063; 29782494; 29945509; 30070096; 30148172; 30178296; 30359286; 30689542; 30923110; 31051301; 31132788; 31199012; 31247189; 31701227; 31729096; 31845438; 32096121; 32120844; 32207552; 32272234; 32445783; 32483437; 32486284; 32560811; 32572885; 32756860; 33028204; 33161932; 33239198; 33617897; 33753553; 34257568; 34288216; 34757486; |
| Motif | |
| Gene Encoded By | |
| Mass | 24,824 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=122 nM for Ub-AMC {ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}; KM=1.20 uM for ubiquitin ethyl ester {ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}; Vmax=0.47 umol/min/mg enzyme toward Ub-AMC {ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}; Vmax=25 umol/min/mg enzyme toward ubiquitin ethyl ester {ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.19.12; |