ID UBP21_HUMAN Reviewed; 565 AA. AC Q9UK80; Q59H60; Q5BKT5; Q5VTW9; Q5VTX0; Q9BTV1; Q9HBS2; Q9NYN4; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 205. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 21 {ECO:0000305}; DE EC=3.4.19.12 {ECO:0000269|PubMed:10799498, ECO:0000269|PubMed:32011234}; DE AltName: Full=Deubiquitinating enzyme 21 {ECO:0000303|PubMed:10799498}; DE AltName: Full=Ubiquitin thioesterase 21 {ECO:0000303|PubMed:10799498}; DE AltName: Full=Ubiquitin-specific-processing protease 21 {ECO:0000303|PubMed:10799498}; GN Name=USP21 {ECO:0000303|PubMed:10799498, ECO:0000312|HGNC:HGNC:12620}; GN Synonyms=USP23 {ECO:0000303|PubMed:10786635}; ORFNames=PP1490; 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 [MRNA] (ISOFORM 1). RX PubMed=10786635; DOI=10.1016/s0167-4781(99)00233-x; RA Smith T.S., Southan C.; RT "Sequencing, tissue distribution and chromosomal assignment of a novel RT ubiquitin-specific protease USP23."; RL Biochim. Biophys. Acta 1490:184-188(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND RP MUTAGENESIS OF CYS-221. RC TISSUE=Placenta; RX PubMed=10799498; DOI=10.1074/jbc.275.19.14212; RA Gong L., Kamitani T., Millas S., Yeh E.T.H.; RT "Identification of a novel isopeptidase with dual specificity for RT ubiquitin- and NEDD8-conjugated proteins."; RL J. Biol. Chem. 275:14212-14216(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X., RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney, Lung, and Testis; 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 [9] RP SUBCELLULAR LOCATION, AND NUCLEAR EXPORT SIGNAL. RX PubMed=21888622; DOI=10.1042/bj20111300; RA Garcia-Santisteban I., Banuelos S., Rodriguez J.A.; RT "A global survey of CRM1-dependent nuclear export sequences in the human RT deubiquitinase family."; RL Biochem. J. 441:209-217(2012). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [11] RP FUNCTION, AND INTERACTION WITH BEND3 AND BAZ2A. RX PubMed=26100909; DOI=10.1073/pnas.1424705112; RA Khan A., Giri S., Wang Y., Chakraborty A., Ghosh A.K., Anantharaman A., RA Aggarwal V., Sathyan K.M., Ha T., Prasanth K.V., Prasanth S.G.; RT "BEND3 represses rDNA transcription by stabilizing a NoRC component via RT USP21 deubiquitinase."; RL Proc. Natl. Acad. Sci. U.S.A. 112:8338-8343(2015). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-221. RX PubMed=32011234; DOI=10.7554/elife.54023; RA Garshott D.M., Sundaramoorthy E., Leonard M., Bennett E.J.; RT "Distinct regulatory ribosomal ubiquitylation events are reversible and RT hierarchically organized."; RL Elife 9:0-0(2020). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) OF 1-75 IN COMPLEX WITH UBIQUITIN RP AND ZINC. RX PubMed=21399617; DOI=10.1038/embor.2011.17; RA Ye Y., Akutsu M., Reyes-Turcu F., Enchev R.I., Wilkinson K.D., Komander D.; RT "Polyubiquitin binding and cross-reactivity in the USP domain RT deubiquitinase USP21."; RL EMBO Rep. 12:350-357(2011). CC -!- FUNCTION: Deubiquitinates histone H2A, a specific tag for epigenetic CC transcriptional repression, thereby acting as a coactivator (By CC similarity). Deubiquitination of histone H2A releaves the repression of CC di- and trimethylation of histone H3 at 'Lys-4', resulting in CC regulation of transcriptional initiation (By similarity). Regulates CC gene expression via histone H2A deubiquitination (By similarity). CC Deubiquitinates BAZ2A/TIP5 leading to its stabilization CC (PubMed:26100909). Also capable of removing NEDD8 from NEDD8 conjugates CC but has no effect on Sentrin-1 conjugates (PubMed:10799498). Also acts CC as a negative regulator of the ribosome quality control (RQC) by CC mediating deubiquitination of 40S ribosomal proteins RPS10/eS10 and CC RPS20/uS10, thereby antagonizing ZNF598-mediated 40S ubiquitination CC (PubMed:32011234). {ECO:0000250|UniProtKB:Q9QZL6, CC ECO:0000269|PubMed:10799498, ECO:0000269|PubMed:26100909, CC ECO:0000269|PubMed:32011234}. 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:10799498, CC ECO:0000269|PubMed:32011234}; CC -!- SUBUNIT: Interacts with BEND3. {ECO:0000269|PubMed:26100909}. CC -!- INTERACTION: CC Q9UK80; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-373242, EBI-10173507; CC Q9UK80; Q16630-2: CPSF6; NbExp=3; IntAct=EBI-373242, EBI-11088043; CC Q9UK80; O95967: EFEMP2; NbExp=3; IntAct=EBI-373242, EBI-743414; CC Q9UK80; Q9NYD6: HOXC10; NbExp=3; IntAct=EBI-373242, EBI-1188075; CC Q9UK80; Q7L273: KCTD9; NbExp=3; IntAct=EBI-373242, EBI-4397613; CC Q9UK80; Q6A162: KRT40; NbExp=3; IntAct=EBI-373242, EBI-10171697; CC Q9UK80; P09936: UCHL1; NbExp=4; IntAct=EBI-373242, EBI-714860; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21888622}. Nucleus CC {ECO:0000269|PubMed:21888622}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9UK80-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UK80-2; Sequence=VSP_036717, VSP_036718; CC Name=3; CC IsoId=Q9UK80-3; Sequence=VSP_036719; CC -!- TISSUE SPECIFICITY: Highly expressed in heart, pancreas and skeletal CC muscle. Also expressed in brain, placenta, liver and kidney, and at CC very low level in lung. {ECO:0000269|PubMed:10799498}. CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP21 subfamily. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF61308.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAG17222.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAD92136.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; 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; AF177758; AAD54321.1; -; mRNA. DR EMBL; AF233442; AAF61308.1; ALT_FRAME; mRNA. DR EMBL; AK292319; BAF85008.1; -; mRNA. DR EMBL; AF217979; AAG17222.1; ALT_FRAME; mRNA. DR EMBL; AB208899; BAD92136.1; ALT_INIT; mRNA. DR EMBL; AL590714; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW52644.1; -; Genomic_DNA. DR EMBL; BC003130; AAH03130.2; -; mRNA. DR EMBL; BC090946; AAH90946.1; -; mRNA. DR EMBL; BC136291; AAI36292.1; -; mRNA. DR CCDS; CCDS30920.1; -. [Q9UK80-1] DR CCDS; CCDS81392.1; -. [Q9UK80-3] DR RefSeq; NP_001014443.1; NM_001014443.2. [Q9UK80-1] DR RefSeq; NP_001306777.1; NM_001319848.1. [Q9UK80-3] DR RefSeq; NP_036607.3; NM_012475.4. [Q9UK80-1] DR PDB; 2Y5B; X-ray; 2.70 A; A/E=196-565. DR PDB; 3I3T; X-ray; 2.59 A; A/C/E/G=209-563. DR PDB; 3MTN; X-ray; 2.70 A; A/C=209-562. DR PDBsum; 2Y5B; -. DR PDBsum; 3I3T; -. DR PDBsum; 3MTN; -. DR AlphaFoldDB; Q9UK80; -. DR SMR; Q9UK80; -. DR BioGRID; 117950; 158. DR DIP; DIP-31255N; -. DR IntAct; Q9UK80; 27. DR MINT; Q9UK80; -. DR STRING; 9606.ENSP00000356981; -. DR BindingDB; Q9UK80; -. DR ChEMBL; CHEMBL2157852; -. DR GuidetoPHARMACOLOGY; 3223; -. DR MEROPS; C19.034; -. DR iPTMnet; Q9UK80; -. DR PhosphoSitePlus; Q9UK80; -. DR BioMuta; USP21; -. DR DMDM; 10720334; -. DR jPOST; Q9UK80; -. DR MassIVE; Q9UK80; -. DR PaxDb; 9606-ENSP00000356981; -. DR PeptideAtlas; Q9UK80; -. DR ProteomicsDB; 84737; -. [Q9UK80-1] DR ProteomicsDB; 84738; -. [Q9UK80-2] DR ProteomicsDB; 84739; -. [Q9UK80-3] DR Antibodypedia; 34297; 362 antibodies from 30 providers. DR DNASU; 27005; -. DR Ensembl; ENST00000289865.12; ENSP00000289865.8; ENSG00000143258.17. [Q9UK80-1] DR Ensembl; ENST00000368001.1; ENSP00000356980.1; ENSG00000143258.17. [Q9UK80-3] DR Ensembl; ENST00000368002.8; ENSP00000356981.3; ENSG00000143258.17. [Q9UK80-1] DR GeneID; 27005; -. DR KEGG; hsa:27005; -. DR MANE-Select; ENST00000368002.8; ENSP00000356981.3; NM_001014443.3; NP_001014443.1. DR UCSC; uc031vci.2; human. [Q9UK80-1] DR AGR; HGNC:12620; -. DR CTD; 27005; -. DR DisGeNET; 27005; -. DR GeneCards; USP21; -. DR HGNC; HGNC:12620; USP21. DR HPA; ENSG00000143258; Low tissue specificity. DR MalaCards; USP21; -. DR MIM; 604729; gene. DR neXtProt; NX_Q9UK80; -. DR OpenTargets; ENSG00000143258; -. DR PharmGKB; PA37246; -. DR VEuPathDB; HostDB:ENSG00000143258; -. DR eggNOG; KOG1868; Eukaryota. DR GeneTree; ENSGT00940000155545; -. DR HOGENOM; CLU_035237_0_0_1; -. DR InParanoid; Q9UK80; -. DR OMA; RYWAQYY; -. DR OrthoDB; 227085at2759; -. DR PhylomeDB; Q9UK80; -. DR TreeFam; TF106277; -. DR BRENDA; 3.4.19.12; 2681. DR PathwayCommons; Q9UK80; -. DR Reactome; R-HSA-5357786; TNFR1-induced proapoptotic signaling. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5357956; TNFR1-induced NF-kappa-B signaling pathway. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR SignaLink; Q9UK80; -. DR SIGNOR; Q9UK80; -. DR BioGRID-ORCS; 27005; 13 hits in 1200 CRISPR screens. DR ChiTaRS; USP21; human. DR EvolutionaryTrace; Q9UK80; -. DR GenomeRNAi; 27005; -. DR Pharos; Q9UK80; Tbio. DR PRO; PR:Q9UK80; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9UK80; Protein. DR Bgee; ENSG00000143258; Expressed in right uterine tube and 192 other cell types or tissues. DR ExpressionAtlas; Q9UK80; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0008234; F:cysteine-type peptidase activity; IMP:UniProtKB. DR GO; GO:0019784; F:deNEDDylase activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; ISS:UniProtKB. DR CDD; cd02674; Peptidase_C19R; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR001394; Peptidase_C19_UCH. DR InterPro; IPR018200; USP_CS. DR InterPro; IPR028889; USP_dom. DR PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR21646:SF6; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 21; 1. DR Pfam; PF00443; UCH; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR PROSITE; PS00972; USP_1; 1. DR PROSITE; PS00973; USP_2; 1. DR PROSITE; PS50235; USP_3; 1. DR Genevisible; Q9UK80; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Chromatin regulator; KW Cytoplasm; Hydrolase; Metal-binding; Nucleus; Protease; Reference proteome; KW Thiol protease; Transcription; Transcription regulation; KW Ubl conjugation pathway; Zinc. FT CHAIN 1..565 FT /note="Ubiquitin carboxyl-terminal hydrolase 21" FT /id="PRO_0000080648" FT DOMAIN 212..558 FT /note="USP" FT REGION 1..103 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 134..152 FT /note="Nuclear export signal" FT /evidence="ECO:0000269|PubMed:21888622" FT COMPBIAS 57..72 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 221 FT /note="Nucleophile" FT /evidence="ECO:0000305|PubMed:10799498, FT ECO:0000305|PubMed:32011234" FT ACT_SITE 518 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092, FT ECO:0000255|PROSITE-ProRule:PRU10093" FT BINDING 384 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21399617, FT ECO:0007744|PDB:2Y5B" FT BINDING 387 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21399617, FT ECO:0007744|PDB:2Y5B" FT BINDING 437 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21399617, FT ECO:0007744|PDB:2Y5B" FT BINDING 440 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21399617, FT ECO:0007744|PDB:2Y5B" FT VAR_SEQ 372..382 FT /note="DLFVGQLKSCL -> GMEWGKAMREN (in isoform 2)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_036717" FT VAR_SEQ 383..565 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_036718" FT VAR_SEQ 498..511 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15498874" FT /id="VSP_036719" FT VARIANT 91 FT /note="P -> S (in dbSNP:rs34779722)" FT /id="VAR_051531" FT VARIANT 321 FT /note="G -> D (in dbSNP:rs17356051)" FT /id="VAR_051532" FT VARIANT 336 FT /note="P -> T (in dbSNP:rs1127525)" FT /id="VAR_051533" FT MUTAGEN 221 FT /note="C->A,S: Abolishes ubiquitin thioesterase activity." FT /evidence="ECO:0000269|PubMed:10799498, FT ECO:0000269|PubMed:32011234" FT CONFLICT 42 FT /note="A -> G (in Ref. 8; AAH90946)" FT /evidence="ECO:0000305" FT CONFLICT 272 FT /note="P -> L (in Ref. 2; AAF61308)" FT /evidence="ECO:0000305" FT CONFLICT 415 FT /note="S -> F (in Ref. 2; AAF61308)" FT /evidence="ECO:0000305" FT STRAND 217..219 FT /evidence="ECO:0007829|PDB:3MTN" FT HELIX 221..231 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 234..242 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 245..248 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 257..268 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 281..290 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 292..294 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 302..317 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 351..365 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 369..374 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 376..384 FT /evidence="ECO:0007829|PDB:3I3T" FT TURN 385..387 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 390..402 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 416..424 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 427..429 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 431..433 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 438..440 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 446..454 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 457..463 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 466..471 FT /evidence="ECO:0007829|PDB:2Y5B" FT STRAND 473..475 FT /evidence="ECO:0007829|PDB:2Y5B" FT HELIX 490..492 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 501..513 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 516..525 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 528..533 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 536..540 FT /evidence="ECO:0007829|PDB:3I3T" FT HELIX 542..546 FT /evidence="ECO:0007829|PDB:3I3T" FT STRAND 551..557 FT /evidence="ECO:0007829|PDB:3I3T" SQ SEQUENCE 565 AA; 62656 MW; 8A13ED34C03B2330 CRC64; MPQASEHRLG RTREPPVNIQ PRVGSKLPFA PRARSKERRN PASGPNPMLR PLPPRPGLPD ERLKKLELGR GRTSGPRPRG PLRADHGVPL PGSPPPTVAL PLPSRTNLAR SKSVSSGDLR PMGIALGGHR GTGELGAALS RLALRPEPPT LRRSTSLRRL GGFPGPPTLF SIRTEPPASH GSFHMISARS SEPFYSDDKM AHHTLLLGSG HVGLRNLGNT CFLNAVLQCL SSTRPLRDFC LRRDFRQEVP GGGRAQELTE AFADVIGALW HPDSCEAVNP TRFRAVFQKY VPSFSGYSQQ DAQEFLKLLM ERLHLEINRR GRRAPPILAN GPVPSPPRRG GALLEEPELS DDDRANLMWK RYLEREDSKI VDLFVGQLKS CLKCQACGYR STTFEVFCDL SLPIPKKGFA GGKVSLRDCF NLFTKEEELE SENAPVCDRC RQKTRSTKKL TVQRFPRILV LHLNRFSASR GSIKKSSVGV DFPLQRLSLG DFASDKAGSP VYQLYALCNH SGSVHYGHYT ALCRCQTGWH VYNDSRVSPV SENQVASSEG YVLFYQLMQE PPRCL //