ID UCHL1_HUMAN Reviewed; 223 AA. AC P09936; Q4W5K6; Q71UM0; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1990, sequence version 2. DT 27-MAR-2024, entry version 240. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase isozyme L1; DE Short=UCH-L1; DE EC=3.4.19.12 {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}; DE AltName: Full=Neuron cytoplasmic protein 9.5; DE AltName: Full=PGP 9.5; DE Short=PGP9.5; DE AltName: Full=Ubiquitin thioesterase L1; DE Flags: Precursor; GN Name=UCHL1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung, and Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-15. RX PubMed=2163617; DOI=10.1042/bj2680521; RA Day I.N.M., Hinks L.J., Thompson R.J.; RT "The structure of the human gene encoding protein gene product 9.5 RT (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase."; RL Biochem. J. 268:521-524(1990). RN [5] RP PROTEIN SEQUENCE OF 1-15 AND 214-221, SUSCEPTIBILITY TO OXIDATION, RP IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY. RX PubMed=14722078; DOI=10.1074/jbc.m314124200; RA Choi J., Levey A.I., Weintraub S.T., Rees H.D., Gearing M., Chin L.-S., RA Li L.; RT "Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal RT hydrolase L1 associated with idiopathic Parkinson's and Alzheimer's RT diseases."; RL J. Biol. Chem. 279:13256-13264(2004). RN [6] RP PROTEIN SEQUENCE OF 1-15; 20-27; 66-78; 84-129; 136-195 AND 214-221, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex; RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-223, AND PARTIAL PROTEIN SEQUENCE. RX PubMed=2947814; DOI=10.1016/0014-5793(87)81327-3; RA Day I.N.M., Thompson R.J.; RT "Molecular cloning of cDNA coding for human PGP 9.5 protein. A novel RT cytoplasmic marker for neurones and neuroendocrine cells."; RL FEBS Lett. 210:157-160(1987). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 16-223, FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, VARIANT PARK5 MET-93, AND CHARACTERIZATION RP OF VARIANT PARK5 MET-93. RX PubMed=9774100; DOI=10.1038/26652; RA Leroy E., Boyer R., Auburger G., Leube B., Ulm G., Mezey E., Harta G., RA Brownstein M.J., Jonnalagada S., Chernova T., Dehejia A., Lavedan C., RA Gasser T., Steinbach P.J., Wilkinson K.D., Polymeropoulos M.H.; RT "The ubiquitin pathway in Parkinson's disease."; RL Nature 395:451-452(1998). RN [9] RP PROTEIN SEQUENCE OF 20-25; 79-81; 106-121 AND 134-151. RX PubMed=1849484; DOI=10.1016/0014-5793(91)80300-r; RA Honore B., Rasmussen H.H., Vandekerckhove J., Celis J.E.; RT "Neuronal protein gene product 9.5 (IEF SSP 6104) is expressed in cultured RT human MRC-5 fibroblasts of normal origin and is strongly down-regulated in RT their SV40 transformed counterparts."; RL FEBS Lett. 280:235-240(1991). RN [10] RP PROTEIN SEQUENCE OF 20-25; 79-91; 106-123 AND 136-151. RX PubMed=1286667; DOI=10.1002/elps.11501301199; RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., RA Vandekerckhove J.; RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein RT database of normal human epidermal keratinocytes."; RL Electrophoresis 13:960-969(1992). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF GLN-73; CYS-90; RP HIS-97; HIS-161 AND ASP-176, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=8639624; DOI=10.1021/bi960099f; RA Larsen C.N., Price J.S., Wilkinson K.D.; RT "Substrate binding and catalysis by ubiquitin C-terminal hydrolases: RT identification of two active site residues."; RL Biochemistry 35:6735-6744(1996). RN [12] RP TISSUE SPECIFICITY. RX PubMed=9790970; DOI=10.1006/bbrc.1998.9532; RA Wada H., Kito K., Caskey L.S., Yeh E.T.H., Kamitani T.; RT "Cleavage of the C-terminus of NEDD8 by UCH-L3."; RL Biochem. Biophys. Res. Commun. 251:688-692(1998). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT PARK5 MET-93, AND RP CHARACTERIZATION OF VARIANT TYR-18. RX PubMed=12408865; DOI=10.1016/s0092-8674(02)01012-7; RA Liu Y., Fallon L., Lashuel H.A., Liu Z., Lansbury P.T. Jr.; RT "The UCH-L1 gene encodes two opposing enzymatic activities that affect RT alpha-synuclein degradation and Parkinson's disease susceptibility."; RL Cell 111:209-218(2002). RN [14] RP INTERACTION WITH COPS5. RX PubMed=12082530; DOI=10.1038/sj.onc.1205390; RA Caballero O.L., Resto V., Patturajan M., Meerzaman D., Guo M.Z., Engles J., RA Yochem R., Ratovitski E., Sidransky D., Jen J.; RT "Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1)."; RL Oncogene 21:3003-3010(2002). RN [15] RP CATALYTIC ACTIVITY, AND ACTIVE SITE. RX PubMed=16475834; DOI=10.1021/bi052135t; RA Case A., Stein R.L.; RT "Mechanistic studies of ubiquitin C-terminal hydrolase L1."; RL Biochemistry 45:2443-2452(2006). RN [16] RP SUBCELLULAR LOCATION, AND ISOPRENYLATION AT CYS-220. RX PubMed=19261853; DOI=10.1073/pnas.0806474106; RA Liu Z., Meray R.K., Grammatopoulos T.N., Fredenburg R.A., Cookson M.R., RA Liu Y., Logan T., Lansbury P.T. Jr.; RT "Membrane-associated farnesylated UCH-L1 promotes alpha-synuclein RT neurotoxicity and is a therapeutic target for Parkinson's disease."; RL Proc. Natl. Acad. Sci. U.S.A. 106:4635-4640(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP FUNCTION. RX PubMed=22212137; DOI=10.1111/j.1471-4159.2011.07644.x; RA Zhang M., Deng Y., Luo Y., Zhang S., Zou H., Cai F., Wada K., Song W.; RT "Control of BACE1 degradation and APP processing by ubiquitin carboxyl- RT terminal hydrolase L1."; RL J. Neurochem. 120:1129-1138(2012). RN [20] RP FUNCTION, CATALYTIC ACTIVITY, VARIANTS SPG79B ALA-7 AND MET-93, RP CHARACTERIZATION OF VARIANT SPG79B ALA-7, AND MUTAGENESIS OF CYS-90. RX PubMed=23359680; DOI=10.1073/pnas.1222732110; RA Bilguvar K., Tyagi N.K., Ozkara C., Tuysuz B., Bakircioglu M., Choi M., RA Delil S., Caglayan A.O., Baranoski J.F., Erturk O., Yalcinkaya C., RA Karacorlu M., Dincer A., Johnson M.H., Mane S., Chandra S.S., Louvi A., RA Boggon T.J., Lifton R.P., Horwich A.L., Gunel M.; RT "Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads RT to early-onset progressive neurodegeneration."; RL Proc. Natl. Acad. Sci. U.S.A. 110:3489-3494(2013). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-90. RX PubMed=25615526; DOI=10.1038/ncomms7153; RA Goto Y., Zeng L., Yeom C.J., Zhu Y., Morinibu A., Shinomiya K., RA Kobayashi M., Hirota K., Itasaka S., Yoshimura M., Tanimoto K., Torii M., RA Sowa T., Menju T., Sonobe M., Kakeya H., Toi M., Date H., Hammond E.M., RA Hiraoka M., Harada H.; RT "UCHL1 provides diagnostic and antimetastatic strategies due to its RT deubiquitinating effect on HIF-1alpha."; RL Nat. Commun. 6:6153-6153(2015). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), AND SUBUNIT. RX PubMed=16537382; DOI=10.1073/pnas.0510403103; RA Das C., Hoang Q.Q., Kreinbring C.A., Luchansky S.J., Meray R.K., Ray S.S., RA Lansbury P.T., Ringe D., Petsko G.A.; RT "Structural basis for conformational plasticity of the Parkinson's disease- RT associated ubiquitin hydrolase UCH-L1."; RL Proc. Natl. Acad. Sci. U.S.A. 103:4675-4680(2006). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF VARIANTS TYR-18 AND MET-93 IN RP COMPLEX WITH UBIQUITIN, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF RP CYS-90 AND PHE-204. RX PubMed=20439756; DOI=10.1073/pnas.0910870107; RA Boudreaux D.A., Maiti T.K., Davies C.W., Das C.; RT "Ubiquitin vinyl methyl ester binding orients the misaligned active site of RT the ubiquitin hydrolase UCHL1 into productive conformation."; RL Proc. Natl. Acad. Sci. U.S.A. 107:9117-9122(2010). RN [24] RP CHARACTERIZATION OF VARIANT PARK5 MET-93, CHARACTERIZATION OF VARIANT RP TYR-18, MUTAGENESIS OF CYS-90, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=12705903; DOI=10.1016/s0006-291x(03)00555-2; RA Nishikawa K., Li H., Kawamura R., Osaka H., Wang Y.-L., Hara Y., RA Hirokawa T., Manago Y., Amano T., Noda M., Aoki S., Wada K.; RT "Alterations of structure and hydrolase activity of parkinsonism-associated RT human ubiquitin carboxyl-terminal hydrolase L1 variants."; RL Biochem. Biophys. Res. Commun. 304:176-183(2003). RN [25] RP VARIANT MET-93. RX PubMed=10454131; DOI=10.1016/s0304-3940(99)00465-6; RA Harhangi B.S., Farrer M.J., Lincoln S., Bonifati V., Meco G., RA De Michele G., Brice A., Durr A., Martinez M., Gasser T., Bereznai B., RA Vaughan J.R., Wood N.W., Hardy J., Oostra B.A., Breteler M.M.; RT "The Ile93Met mutation in the ubiquitin carboxy-terminal-hydrolase-L1 gene RT is not observed in European cases with familial Parkinson's disease."; RL Neurosci. Lett. 270:1-4(1999). RN [26] RP VARIANT TYR-18. RX PubMed=10203348; DOI=10.1097/00001756-199902050-00040; RA Lincoln S., Vaughan J., Wood N., Baker M., Adamson J., Gwinn-Hardy K., RA Lynch T., Hardy J., Farrer M.; RT "Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal RT hydrolase gene in familial Parkinson's disease."; RL NeuroReport 10:427-429(1999). RN [27] RP VARIANT TYR-18. RX PubMed=11027850; DOI=10.1016/s0304-3940(00)01510-x; RA Mellick G.D., Silburn P.A.; RT "The ubiquitin carboxy-terminal hydrolase-L1 gene S18Y polymorphism does RT not confer protection against idiopathic Parkinson's disease."; RL Neurosci. Lett. 293:127-130(2000). RN [28] RP VARIANT TYR-18. RX PubMed=15048890; DOI=10.1002/ana.20017; RG UCHL1 global genetics consortium; RA Maraganore D.M., Lesnick T.G., Elbaz A., Chartier-Harlin M.-C., Gasser T., RA Krueger R., Hattori N., Mellick G.D., Quattrone A., Satoh J., Toda T., RA Wang J., Ioannidis J.P.A., de Andrade M., Rocca W.A.; RT "UCHL1 is a Parkinson's disease susceptibility gene."; RL Ann. Neurol. 55:512-521(2004). RN [29] RP ERRATUM OF PUBMED:15048890. RG UCHL1 global genetics consortium; RA Maraganore D.M., Lesnick T.G., Elbaz A., Chartier-Harlin M.-C., Gasser T., RA Krueger R., Hattori N., Mellick G.D., Quattrone A., Satoh J., Toda T., RA Wang J., Ioannidis J.P.A., de Andrade M., Rocca W.A.; RL Ann. Neurol. 55:899-899(2004). RN [30] RP VARIANT TYR-18, AND LACK OF ASSOCIATION OF VARIANT TYR-18 WITH PARKINSON RP DISEASE. RX PubMed=16450370; DOI=10.1002/ana.20757; RA Healy D.G., Abou-Sleiman P.M., Casas J.P., Ahmadi K.R., Lynch T., RA Gandhi S., Muqit M.M., Foltynie T., Barker R., Bhatia K.P., Quinn N.P., RA Lees A.J., Gibson J.M., Holton J.L., Revesz T., Goldstein D.B., Wood N.W.; RT "UCHL-1 is not a Parkinson's disease susceptibility gene."; RL Ann. Neurol. 59:627-633(2006). RN [31] RP CHARACTERIZATION OF VARIANT TYR-18, AND ANTIOXIDANT FUNCTION IN NEURONAL RP CELLS. RX PubMed=18411255; DOI=10.1093/hmg/ddn115; RA Kyratzi E., Pavlaki M., Stefanis L.; RT "The S18Y polymorphic variant of UCH-L1 confers an antioxidant function to RT neuronal cells."; RL Hum. Mol. Genet. 17:2160-2171(2008). RN [32] RP VARIANT TYR-18. RX PubMed=21268678; DOI=10.3109/13816810.2010.544360; RA Rudolph T., Sjolander A., Palmer M.S., Minthon L., Wallin A., Andreasen N., RA Tasa G., Juronen E., Blennow K., Zetterberg H., Zetterberg M.; RT "Ubiquitin carboxyl-terminal esterase L1 (UCHL1) S18Y polymorphism in RT patients with cataracts."; RL Ophthalmic Genet. 32:75-79(2011). RN [33] RP VARIANTS SPG79B GLN-178 AND ASP-216, AND CHARACTERIZATION OF VARIANTS RP SPG79B GLN-178 AND ASP-216. RX PubMed=28007905; DOI=10.1093/hmg/ddw391; RA Rydning S.L., Backe P.H., Sousa M.M., Iqbal Z., Oeye A.M., Sheng Y., RA Yang M., Lin X., Slupphaug G., Nordenmark T.H., Vigeland M.D., Bjoeraas M., RA Tallaksen C.M., Selmer K.K.; RT "Novel UCHL1 mutations reveal new insights into ubiquitin processing."; RL Hum. Mol. Genet. 26:1031-1040(2017). RN [34] RP VARIANTS SPG79A 2-GLN--ALA-223 DEL; 25-GLN--ALA-223 DEL; LEU-52 INS; RP 178-ARG--ALA-223 DEL AND 211-GLU--ALA-223 DEL, AND INVOLVEMENT IN SPG79A. RX PubMed=35986737; DOI=10.1016/j.gim.2022.07.006; RG Genomics England Research Consortium; RA Park J., Tucci A., Cipriani V., Demidov G., Rocca C., Senderek J., RA Butryn M., Velic A., Lam T., Galanaki E., Cali E., Vestito L., RA Maroofian R., Deininger N., Rautenberg M., Admard J., Hahn G.A., RA Bartels C., van Os N.J.H., Horvath R., Chinnery P.F., Tiet M.Y., RA Hewamadduma C., Hadjivassiliou M., Tofaris G.K., Wood N.W., Hayer S.N., RA Bender F., Menden B., Cordts I., Klein K., Nguyen H.P., Krauss J.K., RA Blahak C., Strom T.M., Sturm M., van de Warrenburg B., Lerche H., Macek B., RA Synofzik M., Ossowski S., Timmann D., Wolf M.E., Smedley D., Riess O., RA Schoels L., Houlden H., Haack T.B., Hengel H.; RT "Heterozygous UCHL1 loss-of-function variants cause a neurodegenerative RT disorder with spasticity, ataxia, neuropathy, and optic atrophy."; RL Genet. Med. 24:2079-2090(2022). CC -!- FUNCTION: Deubiquitinase that plays a role in the regulation of several CC processes such as maintenance of synaptic function, cardiac function, CC inflammatory response or osteoclastogenesis (PubMed:22212137, CC PubMed:23359680). Abrogates the ubiquitination of multiple proteins CC including WWTR1/TAZ, EGFR, HIF1A and beta-site amyloid precursor CC protein cleaving enzyme 1/BACE1 (PubMed:22212137, PubMed:25615526). In CC addition, recognizes and hydrolyzes a peptide bond at the C-terminal CC glycine of ubiquitin to maintain a stable pool of monoubiquitin that is CC a key requirement for the ubiquitin-proteasome and the autophagy- CC lysosome pathways (PubMed:9774100, PubMed:8639624, PubMed:12408865). CC Regulates amyloid precursor protein/APP processing by promoting BACE1 CC degradation resulting in decreased amyloid beta production CC (PubMed:22212137). Plays a role in the immune response by regulating CC the ability of MHC I molecules to reach cross-presentation compartments CC competent for generating Ag-MHC I complexes (By similarity). Mediates CC the 'Lys-48'-linked deubiquitination of the transcriptional coactivator CC WWTR1/TAZ leading to its stabilization and inhibition of CC osteoclastogenesis (By similarity). Deubiquitinates and stabilizes CC epidermal growth factor receptor EGFR to prevent its degradation and to CC activate its downstream mediators (By similarity). Modulates oxidative CC activity in skeletal muscle by regulating key mitochondrial oxidative CC proteins (By similarity). Enhances the activity of hypoxia-inducible CC factor 1-alpha/HIF1A by abrogateing its VHL E3 ligase-mediated CC ubiquitination and consequently inhibiting its degradation CC (PubMed:25615526). {ECO:0000250|UniProtKB:Q9R0P9, CC ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:22212137, CC ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:25615526, CC ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76- CC residue protein attached to proteins as an intracellular targeting CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:12408865, CC ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:16475834, CC ECO:0000269|PubMed:20439756, ECO:0000269|PubMed:23359680, CC ECO:0000269|PubMed:25615526, ECO:0000269|PubMed:8639624, CC ECO:0000269|PubMed:9774100}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=122 nM for Ub-AMC {ECO:0000269|PubMed:12705903, CC ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}; CC KM=1.2 uM for ubiquitin ethyl ester {ECO:0000269|PubMed:12705903, CC ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}; CC Vmax=0.47 umol/min/mg enzyme toward Ub-AMC CC {ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:8639624, CC ECO:0000269|PubMed:9774100}; CC Vmax=25 umol/min/mg enzyme toward ubiquitin ethyl ester CC {ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:8639624, CC ECO:0000269|PubMed:9774100}; CC -!- SUBUNIT: Monomer. Homodimer. Interacts with SNCA (By similarity). CC Interacts with COPS5. {ECO:0000250, ECO:0000269|PubMed:12082530, CC ECO:0000269|PubMed:16537382, ECO:0000269|PubMed:20439756}. CC -!- INTERACTION: CC P09936; P63010-2: AP2B1; NbExp=3; IntAct=EBI-714860, EBI-11529439; CC P09936; P05067: APP; NbExp=5; IntAct=EBI-714860, EBI-77613; CC P09936; P05067-2: APP; NbExp=3; IntAct=EBI-714860, EBI-17264467; CC P09936; Q8N6T3-3: ARFGAP1; NbExp=3; IntAct=EBI-714860, EBI-10694449; CC P09936; P18847: ATF3; NbExp=3; IntAct=EBI-714860, EBI-712767; CC P09936; Q9H1Y0: ATG5; NbExp=3; IntAct=EBI-714860, EBI-1047414; CC P09936; O15392: BIRC5; NbExp=3; IntAct=EBI-714860, EBI-518823; CC P09936; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-714860, EBI-2837444; CC P09936; P83916: CBX1; NbExp=4; IntAct=EBI-714860, EBI-78129; CC P09936; P11802: CDK4; NbExp=4; IntAct=EBI-714860, EBI-295644; CC P09936; Q00535: CDK5; NbExp=2; IntAct=EBI-714860, EBI-1041567; CC P09936; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-714860, EBI-350590; CC P09936; Q92905: COPS5; NbExp=3; IntAct=EBI-714860, EBI-594661; CC P09936; P00533: EGFR; NbExp=3; IntAct=EBI-714860, EBI-297353; CC P09936; O60739: EIF1B; NbExp=3; IntAct=EBI-714860, EBI-1043343; CC P09936; Q8TC29: ENKUR; NbExp=3; IntAct=EBI-714860, EBI-9246952; CC P09936; Q9UI08-2: EVL; NbExp=3; IntAct=EBI-714860, EBI-6448852; CC P09936; Q8WVV9-3: HNRNPLL; NbExp=3; IntAct=EBI-714860, EBI-25845242; CC P09936; Q14164: IKBKE; NbExp=3; IntAct=EBI-714860, EBI-307369; CC P09936; Q6DN90-2: IQSEC1; NbExp=3; IntAct=EBI-714860, EBI-21911304; CC P09936; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-714860, EBI-11985629; CC P09936; P13473-2: LAMP2; NbExp=3; IntAct=EBI-714860, EBI-21591415; CC P09936; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-714860, EBI-1108377; CC P09936; O95777: LSM8; NbExp=3; IntAct=EBI-714860, EBI-347779; CC P09936; A4FUJ8: MKL1; NbExp=3; IntAct=EBI-714860, EBI-21250407; CC P09936; Q15843: NEDD8; NbExp=4; IntAct=EBI-714860, EBI-716247; CC P09936; O15381-5: NVL; NbExp=3; IntAct=EBI-714860, EBI-18577082; CC P09936; Q9BR81: PCDHGC3; NbExp=3; IntAct=EBI-714860, EBI-22012354; CC P09936; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-714860, EBI-716063; CC P09936; P62826: RAN; NbExp=3; IntAct=EBI-714860, EBI-286642; CC P09936; Q8TAI7: RHEBL1; NbExp=3; IntAct=EBI-714860, EBI-746555; CC P09936; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-714860, EBI-25829984; CC P09936; Q15554-4: TERF2; NbExp=3; IntAct=EBI-714860, EBI-25840535; CC P09936; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-714860, EBI-750109; CC P09936; P04637: TP53; NbExp=3; IntAct=EBI-714860, EBI-366083; CC P09936; Q9Y4K3: TRAF6; NbExp=3; IntAct=EBI-714860, EBI-359276; CC P09936; P19474: TRIM21; NbExp=3; IntAct=EBI-714860, EBI-81290; CC P09936; Q9BSL1: UBAC1; NbExp=3; IntAct=EBI-714860, EBI-749370; CC P09936; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-714860, EBI-10180829; CC P09936; P61086: UBE2K; NbExp=3; IntAct=EBI-714860, EBI-473850; CC P09936; Q9UK80: USP21; NbExp=4; IntAct=EBI-714860, EBI-373242; CC P09936; Q86WB0-2: ZC3HC1; NbExp=3; IntAct=EBI-714860, EBI-25894765; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19261853}. CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:19261853}; Lipid- CC anchor {ECO:0000269|PubMed:19261853}. Note=About 30% of total UCHL1 is CC associated with membranes in brain. Localizes near and/or within CC mitochondria to potentially interact with mitochondrial proteins. CC {ECO:0000250|UniProtKB:Q9R0P9}. CC -!- TISSUE SPECIFICITY: Found in neuronal cell bodies and processes CC throughout the neocortex (at protein level). Expressed in neurons and CC cells of the diffuse neuroendocrine system and their tumors. Weakly CC expressed in ovary. Down-regulated in brains from Parkinson disease and CC Alzheimer disease patients. {ECO:0000269|PubMed:14722078, CC ECO:0000269|PubMed:9790970}. CC -!- PTM: O-glycosylated. {ECO:0000250}. CC -!- DISEASE: Parkinson disease 5 (PARK5) [MIM:613643]: A complex CC neurodegenerative disorder with manifestations ranging from typical CC Parkinson disease to dementia with Lewy bodies. Clinical features CC include parkinsonian symptoms (resting tremor, rigidity, postural CC instability and bradykinesia), dementia, diffuse Lewy body pathology, CC autonomic dysfunction, hallucinations and paranoia. CC {ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:12705903, CC ECO:0000269|PubMed:9774100}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- DISEASE: Spastic paraplegia 79A, autosomal dominant, with ataxia CC (SPG79A) [MIM:620221]: A form of spastic paraplegia, a CC neurodegenerative disorder characterized by a slow, gradual, CC progressive weakness and spasticity of the lower limbs. Rate of CC progression and the severity of symptoms are quite variable. Initial CC symptoms may include difficulty with balance, weakness and stiffness in CC the legs, muscle spasms, and dragging the toes when walking. In some CC forms of the disorder, bladder symptoms (such as incontinence) may CC appear, or the weakness and stiffness may spread to other parts of the CC body. SPG79A is a slowly progressive form characterized by late-onset CC spastic ataxia, neuropathy, and often optic atrophy. CC {ECO:0000269|PubMed:35986737}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Spastic paraplegia 79B, autosomal recessive (SPG79B) CC [MIM:615491]: A form of spastic paraplegia, a neurodegenerative CC disorder characterized by a slow, gradual, progressive weakness and CC spasticity of the lower limbs. Rate of progression and the severity of CC symptoms are quite variable. Initial symptoms may include difficulty CC with balance, weakness and stiffness in the legs, muscle spasms, and CC dragging the toes when walking. In some forms of the disorder, bladder CC symptoms (such as incontinence) may appear, or the weakness and CC stiffness may spread to other parts of the body. SPG79B is CC characterized by childhood onset blindness, cerebellar ataxia, CC nystagmus, dorsal column dysfunction, and spasticity with upper motor CC neuron dysfunction. {ECO:0000269|PubMed:23359680, CC ECO:0000269|PubMed:28007905}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Oxidation of Met-1, Met-6, Met-12, Met-124 and Met-179 CC to methionine sulfoxide, and oxidation of Cys-220 to cysteine sulfonic CC acid have been observed in brains from Alzheimer disease (AD) and CC Parkinson disease (PD) patients. In AD, UCHL1 was found to be CC associated with neurofibrillary tangles. In contrast to UCHL3, does not CC hydrolyze a peptide bond at the C-terminal glycine of NEDD8. CC -!- SIMILARITY: Belongs to the peptidase C12 family. {ECO:0000305}. CC -!- CAUTION: PubMed:9774100 reports the association of mutation Ile93Met CC with Parkinson disease. However, according to PubMed:16450370 this CC association is uncertain and UCHL1 is not a susceptibility gene for CC Parkinson disease. {ECO:0000305}. CC -!- CAUTION: The oxidation forms of Met-1, Met-6, Met-12, Met-124, Met-179 CC and Cys-220 are subject of controversy and could be the artifactual CC results of sample handling. {ECO:0000305|PubMed:14722078}. CC -!- CAUTION: The homodimer may have ATP-independent ubiquitin ligase CC activity (PubMed:12408865). However, in another study, UCHL1 was shown CC to lack ubiquitin ligase activity (PubMed:23359680). CC {ECO:0000269|PubMed:23359680, ECO:0000305|PubMed:12408865}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA28443.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ubiquitin carboxy-terminal hydrolase CC L1 entry; CC URL="https://en.wikipedia.org/wiki/Ubiquitin_carboxy-terminal_hydrolase_L1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AC095043; AAY40923.1; -; Genomic_DNA. DR EMBL; CH471069; EAW92983.1; -; Genomic_DNA. DR EMBL; BC000332; AAH00332.1; -; mRNA. DR EMBL; BC005117; AAH05117.1; -; mRNA. DR EMBL; BC006305; AAH06305.1; -; mRNA. DR EMBL; X17377; CAA35249.1; -; Genomic_DNA. DR EMBL; X04741; CAA28443.1; ALT_INIT; mRNA. DR EMBL; AH007277; AAD09172.1; -; Genomic_DNA. DR CCDS; CCDS3462.1; -. DR PIR; A25856; A25856. DR RefSeq; NP_004172.2; NM_004181.4. DR PDB; 2ETL; X-ray; 2.40 A; A/B=1-223. DR PDB; 2LEN; NMR; -; A=1-223. DR PDB; 3IFW; X-ray; 2.40 A; A=1-223. DR PDB; 3IRT; X-ray; 2.80 A; A/B=1-223. DR PDB; 3KVF; X-ray; 2.80 A; A=1-223. DR PDB; 3KW5; X-ray; 2.83 A; A=1-223. DR PDB; 4DM9; X-ray; 2.35 A; A/B=1-223. DR PDB; 4JKJ; X-ray; 2.15 A; A/B=1-223. DR PDB; 7ZM0; X-ray; 2.24 A; A/B/C/D/E/F/G/H/I/J=1-223. DR PDB; 8DY8; X-ray; 2.10 A; A/B=1-223. DR PDB; 8EDE; X-ray; 1.80 A; A/B=1-223. DR PDBsum; 2ETL; -. DR PDBsum; 2LEN; -. DR PDBsum; 3IFW; -. DR PDBsum; 3IRT; -. DR PDBsum; 3KVF; -. DR PDBsum; 3KW5; -. DR PDBsum; 4DM9; -. DR PDBsum; 4JKJ; -. DR PDBsum; 7ZM0; -. DR PDBsum; 8DY8; -. DR PDBsum; 8EDE; -. DR AlphaFoldDB; P09936; -. DR BMRB; P09936; -. DR SMR; P09936; -. DR BioGRID; 113192; 241. DR CORUM; P09936; -. DR DIP; DIP-36620N; -. DR IntAct; P09936; 88. DR MINT; P09936; -. DR STRING; 9606.ENSP00000284440; -. DR BindingDB; P09936; -. DR ChEMBL; CHEMBL6159; -. DR DrugBank; DB12695; Phenethyl Isothiocyanate. DR GuidetoPHARMACOLOGY; 2426; -. DR MEROPS; C12.001; -. DR GlyGen; P09936; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P09936; -. DR MetOSite; P09936; -. DR PhosphoSitePlus; P09936; -. DR SwissPalm; P09936; -. DR BioMuta; UCHL1; -. DR DMDM; 136681; -. DR DOSAC-COBS-2DPAGE; P09936; -. DR CPTAC; CPTAC-601; -. DR CPTAC; CPTAC-602; -. DR EPD; P09936; -. DR jPOST; P09936; -. DR MassIVE; P09936; -. DR PaxDb; 9606-ENSP00000284440; -. DR PeptideAtlas; P09936; -. DR ProteomicsDB; 52282; -. DR Pumba; P09936; -. DR TopDownProteomics; P09936; -. DR Antibodypedia; 1062; 2580 antibodies from 53 providers. DR DNASU; 7345; -. DR Ensembl; ENST00000284440.9; ENSP00000284440.4; ENSG00000154277.13. DR Ensembl; ENST00000503431.5; ENSP00000422542.1; ENSG00000154277.13. DR GeneID; 7345; -. DR KEGG; hsa:7345; -. DR MANE-Select; ENST00000284440.9; ENSP00000284440.4; NM_004181.5; NP_004172.2. DR AGR; HGNC:12513; -. DR CTD; 7345; -. DR DisGeNET; 7345; -. DR GeneCards; UCHL1; -. DR HGNC; HGNC:12513; UCHL1. DR HPA; ENSG00000154277; Group enriched (brain, pituitary gland). DR MalaCards; UCHL1; -. DR MIM; 191342; gene. DR MIM; 613643; phenotype. DR MIM; 615491; phenotype. DR MIM; 620221; phenotype. DR neXtProt; NX_P09936; -. DR OpenTargets; ENSG00000154277; -. DR Orphanet; 352654; Early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome. DR Orphanet; 2828; Young-onset Parkinson disease. DR PharmGKB; PA37160; -. DR VEuPathDB; HostDB:ENSG00000154277; -. DR eggNOG; KOG1415; Eukaryota. DR GeneTree; ENSGT00940000157306; -. DR HOGENOM; CLU_054406_2_0_1; -. DR InParanoid; P09936; -. DR OMA; KGQDGHL; -. DR OrthoDB; 179179at2759; -. DR PhylomeDB; P09936; -. DR TreeFam; TF316166; -. DR BRENDA; 3.4.19.12; 2681. DR PathwayCommons; P09936; -. DR Reactome; R-HSA-5689603; UCH proteinases. DR SABIO-RK; P09936; -. DR SignaLink; P09936; -. DR SIGNOR; P09936; -. DR BioGRID-ORCS; 7345; 9 hits in 1196 CRISPR screens. DR ChiTaRS; UCHL1; human. DR EvolutionaryTrace; P09936; -. DR GeneWiki; Ubiquitin_carboxy-terminal_hydrolase_L1; -. DR GenomeRNAi; 7345; -. DR Pharos; P09936; Tchem. DR PRO; PR:P09936; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P09936; Protein. DR Bgee; ENSG00000154277; Expressed in pons and 169 other cell types or tissues. DR ExpressionAtlas; P09936; baseline and differential. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0044306; C:neuron projection terminus; IEA:Ensembl. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0031694; F:alpha-2A adrenergic receptor binding; IPI:BHF-UCL. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0008242; F:omega peptidase activity; IDA:UniProtKB. DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl. DR GO; GO:0007412; P:axon target recognition; IEA:Ensembl. DR GO; GO:0019896; P:axonal transport of mitochondrion; IEA:Ensembl. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0042755; P:eating behavior; IEA:Ensembl. DR GO; GO:0002176; P:male germ cell proliferation; IEA:Ensembl. DR GO; GO:0055001; P:muscle cell development; IEA:Ensembl. DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IDA:BHF-UCL. DR GO; GO:0050905; P:neuromuscular process; IEA:Ensembl. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; NAS:ParkinsonsUK-UCL. DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB. DR GO; GO:0016241; P:regulation of macroautophagy; TAS:ParkinsonsUK-UCL. DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl. DR CDD; cd09616; Peptidase_C12_UCH_L1_L3; 1. DR Gene3D; 3.40.532.10; Peptidase C12, ubiquitin carboxyl-terminal hydrolase; 1. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR001578; Peptidase_C12_UCH. DR InterPro; IPR036959; Peptidase_C12_UCH_sf. DR PANTHER; PTHR10589; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR10589:SF19; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE ISOZYME L1; 1. DR Pfam; PF01088; Peptidase_C12; 1. DR PRINTS; PR00707; UBCTHYDRLASE. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR PROSITE; PS00140; UCH_1; 1. DR UCD-2DPAGE; P09936; -. DR Genevisible; P09936; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Direct protein sequencing; Disease variant; KW Endoplasmic reticulum; Glycoprotein; Hereditary spastic paraplegia; KW Hydrolase; Lipoprotein; Membrane; Neurodegeneration; Oxidation; KW Parkinson disease; Parkinsonism; Phosphoprotein; Prenylation; Protease; KW Reference proteome; Thiol protease; Ubl conjugation pathway. FT CHAIN 1..220 FT /note="Ubiquitin carboxyl-terminal hydrolase isozyme L1" FT /id="PRO_0000211055" FT PROPEP 221..223 FT /note="Removed in mature form" FT /evidence="ECO:0000305" FT /id="PRO_0000414311" FT REGION 5..10 FT /note="Interaction with ubiquitin" FT /evidence="ECO:0000269|PubMed:20439756" FT REGION 211..216 FT /note="Interaction with ubiquitin" FT /evidence="ECO:0000269|PubMed:20439756" FT ACT_SITE 90 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:20439756" FT ACT_SITE 161 FT /note="Proton donor" FT /evidence="ECO:0000269|PubMed:20439756" FT SITE 1 FT /note="Susceptible to oxidation" FT /evidence="ECO:0000269|PubMed:14722078" FT SITE 6 FT /note="Susceptible to oxidation" FT /evidence="ECO:0000269|PubMed:14722078" FT SITE 12 FT /note="Susceptible to oxidation" FT /evidence="ECO:0000269|PubMed:14722078" FT SITE 124 FT /note="Susceptible to oxidation" FT /evidence="ECO:0000269|PubMed:14722078" FT SITE 176 FT /note="Important for enzyme activity" FT /evidence="ECO:0000269|PubMed:8639624" FT SITE 179 FT /note="Susceptible to oxidation" FT /evidence="ECO:0000269|PubMed:14722078" FT SITE 220 FT /note="Susceptible to oxidation" FT /evidence="ECO:0000269|PubMed:14722078" FT MOD_RES 125 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q00981" FT LIPID 220 FT /note="S-farnesyl cysteine" FT /evidence="ECO:0000269|PubMed:19261853" FT VARIANT 2..223 FT /note="Missing (in SPG79A)" FT /evidence="ECO:0000269|PubMed:35986737" FT /id="VAR_087898" FT VARIANT 7 FT /note="E -> A (in SPG79B; has decreased binding to FT ubiquitin and significantly decreased hydrolase activity FT compared to wild-type; dbSNP:rs397515634)" FT /evidence="ECO:0000269|PubMed:23359680" FT /id="VAR_070875" FT VARIANT 18 FT /note="S -> Y (it confers protection from oxidative stress FT when expressed at physiological levels in neuroblastoma FT cells and primary cortical neurons; loss of dimerization FT ability; impaired ligase activity; dbSNP:rs5030732)" FT /evidence="ECO:0000269|PubMed:10203348, FT ECO:0000269|PubMed:11027850, ECO:0000269|PubMed:12408865, FT ECO:0000269|PubMed:12705903, ECO:0000269|PubMed:15048890, FT ECO:0000269|PubMed:16450370, ECO:0000269|PubMed:18411255, FT ECO:0000269|PubMed:21268678" FT /id="VAR_015677" FT VARIANT 25..223 FT /note="Missing (in SPG79A)" FT /evidence="ECO:0000269|PubMed:35986737" FT /id="VAR_087899" FT VARIANT 52 FT /note="L -> LL (in SPG79A; uncertain significance)" FT /evidence="ECO:0000269|PubMed:35986737" FT /id="VAR_087900" FT VARIANT 93 FT /note="I -> M (in PARK5; impaired enzymatic hydrolase FT activity; has about a 50% reduction in catalytic activity FT compared to wild-type protein; dbSNP:rs121917767)" FT /evidence="ECO:0000269|PubMed:10454131, FT ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:12705903, FT ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:9774100" FT /id="VAR_015678" FT VARIANT 178..223 FT /note="Missing (in SPG79A)" FT /evidence="ECO:0000269|PubMed:35986737" FT /id="VAR_087901" FT VARIANT 178 FT /note="R -> Q (in SPG79B; increased hydrolase activity; FT decreased protein abundance; dbSNP:rs768996179)" FT /evidence="ECO:0000269|PubMed:28007905" FT /id="VAR_078119" FT VARIANT 211..223 FT /note="Missing (in SPG79A)" FT /evidence="ECO:0000269|PubMed:35986737" FT /id="VAR_087902" FT VARIANT 216 FT /note="A -> D (in SPG79B; decreased protein abundance; FT dbSNP:rs1057519600)" FT /evidence="ECO:0000269|PubMed:28007905" FT /id="VAR_078120" FT MUTAGEN 73 FT /note="Q->R: No effect on enzymatic parameters." FT /evidence="ECO:0000269|PubMed:8639624" FT MUTAGEN 90 FT /note="C->S: Abolishes enzymatic activity." FT /evidence="ECO:0000269|PubMed:12705903, FT ECO:0000269|PubMed:20439756, ECO:0000269|PubMed:23359680, FT ECO:0000269|PubMed:25615526, ECO:0000269|PubMed:8639624" FT MUTAGEN 97 FT /note="H->Q,N: 2-fold increase in affinity for ubiquitin FT ethyl ester, slight reduction in enzymatic activity." FT /evidence="ECO:0000269|PubMed:8639624" FT MUTAGEN 161 FT /note="H->D: 10000-fold decrease in enzymatic activity; no FT change in affinity for ubiquitin ethyl ester." FT /evidence="ECO:0000269|PubMed:8639624" FT MUTAGEN 161 FT /note="H->K,Q,N,Y: Abolishes enzymatic activity." FT /evidence="ECO:0000269|PubMed:8639624" FT MUTAGEN 176 FT /note="D->N: 6-fold decrease in affinity for ubiquitin FT ethyl ester; 97.5% decrease in enzymatic activity." FT /evidence="ECO:0000269|PubMed:8639624" FT MUTAGEN 204 FT /note="F->A: Almost complete loss of activity." FT /evidence="ECO:0000269|PubMed:20439756" FT HELIX 10..19 FT /evidence="ECO:0007829|PDB:4JKJ" FT STRAND 22..30 FT /evidence="ECO:0007829|PDB:4JKJ" FT HELIX 36..38 FT /evidence="ECO:0007829|PDB:4JKJ" FT STRAND 39..42 FT /evidence="ECO:0007829|PDB:4JKJ" FT STRAND 46..54 FT /evidence="ECO:0007829|PDB:4JKJ" FT HELIX 57..70 FT /evidence="ECO:0007829|PDB:4JKJ" FT TURN 71..74 FT /evidence="ECO:0007829|PDB:4JKJ" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:2LEN" FT HELIX 90..100 FT /evidence="ECO:0007829|PDB:4JKJ" FT TURN 101..105 FT /evidence="ECO:0007829|PDB:4JKJ" FT HELIX 113..120 FT /evidence="ECO:0007829|PDB:4JKJ" FT TURN 121..123 FT /evidence="ECO:0007829|PDB:4JKJ" FT HELIX 126..134 FT /evidence="ECO:0007829|PDB:4JKJ" FT HELIX 137..147 FT /evidence="ECO:0007829|PDB:4JKJ" FT STRAND 160..168 FT /evidence="ECO:0007829|PDB:4JKJ" FT STRAND 171..175 FT /evidence="ECO:0007829|PDB:4JKJ" FT STRAND 179..181 FT /evidence="ECO:0007829|PDB:4JKJ" FT STRAND 183..187 FT /evidence="ECO:0007829|PDB:4JKJ" FT HELIX 190..192 FT /evidence="ECO:0007829|PDB:4JKJ" FT HELIX 193..207 FT /evidence="ECO:0007829|PDB:4JKJ" FT HELIX 211..213 FT /evidence="ECO:0007829|PDB:2LEN" FT STRAND 215..221 FT /evidence="ECO:0007829|PDB:4JKJ" SQ SEQUENCE 223 AA; 24824 MW; C9E972AC4DA5DA8A CRC64; MQLKPMEINP EMLNKVLSRL GVAGQWRFVD VLGLEEESLG SVPAPACALL LLFPLTAQHE NFRKKQIEEL KGQEVSPKVY FMKQTIGNSC GTIGLIHAVA NNQDKLGFED GSVLKQFLSE TEKMSPEDRA KCFEKNEAIQ AAHDAVAQEG QCRVDDKVNF HFILFNNVDG HLYELDGRMP FPVNHGASSE DTLLKDAAKV CREFTEREQG EVRFSAVALC KAA //