UBP28_HUMAN
ID UBP28_HUMAN Reviewed; 1077 AA.
AC Q96RU2; B0YJC0; B0YJC1; Q6NZX9; Q9P213;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 28;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 28;
DE AltName: Full=Ubiquitin thioesterase 28;
DE AltName: Full=Ubiquitin-specific-processing protease 28;
GN Name=USP28; Synonyms=KIAA1515;
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=11597335; DOI=10.1186/gb-2001-2-10-research0043;
RA Valero R., Bayes M., Francisca Sanchez-Font M., Gonzalez-Angulo O.,
RA Gonzalez-Duarte R., Marfany G.;
RT "Characterization of alternatively spliced products and tissue-specific
RT isoforms of USP28 and USP25.";
RL Genome Biol. 2:RESEARCH0043.1-RESEARCH0043.10(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Eye;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 289-1077 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [7]
RP FUNCTION, INTERACTION WITH TP53BP1, PHOSPHORYLATION AT SER-67 AND SER-714,
RP AND MUTAGENESIS OF CYS-171.
RX PubMed=16901786; DOI=10.1016/j.cell.2006.06.039;
RA Zhang D., Zaugg K., Mak T.W., Elledge S.J.;
RT "A role for the deubiquitinating enzyme USP28 in control of the DNA-damage
RT response.";
RL Cell 126:529-542(2006).
RN [8]
RP FUNCTION, AND INTERACTION WITH FBXW7.
RX PubMed=17873522; DOI=10.4161/cc.6.19.4804;
RA Popov N., Herold S., Llamazares M., Schulein C., Eilers M.;
RT "Fbw7 and Usp28 regulate myc protein stability in response to DNA damage.";
RL Cell Cycle 6:2327-2331(2007).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FBXW7, AND MUTAGENESIS OF
RP CYS-171.
RX PubMed=17558397; DOI=10.1038/ncb1601;
RA Popov N., Wanzel M., Madiredjo M., Zhang D., Beijersbergen R., Bernards R.,
RA Moll R., Elledge S.J., Eilers M.;
RT "The ubiquitin-specific protease USP28 is required for MYC stability.";
RL Nat. Cell Biol. 9:765-774(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [11]
RP FUNCTION.
RX PubMed=18662541; DOI=10.1016/j.cell.2008.05.043;
RA Bassermann F., Frescas D., Guardavaccaro D., Busino L., Peschiaroli A.,
RA Pagano M.;
RT "The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response
RT checkpoint.";
RL Cell 134:256-267(2008).
RN [12]
RP DEGRADATION, AND INDUCTION.
RX PubMed=20046830; DOI=10.1371/journal.pone.0008531;
RA Li Q., Kluz T., Sun H., Costa M.;
RT "Mechanisms of c-myc degradation by nickel compounds and hypoxia.";
RL PLoS ONE 4:E8531-E8531(2009).
RN [13]
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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [15]
RP FUNCTION, INTERACTION WITH PRKD1 AND ZNF304, PHOSPHORYLATION, MUTAGENESIS
RP OF CYS-171 AND SER-899, AND INDUCTION.
RX PubMed=24623306; DOI=10.7554/elife.02313;
RA Serra R.W., Fang M., Park S.M., Hutchinson L., Green M.R.;
RT "A KRAS-directed transcriptional silencing pathway that mediates the CpG
RT island methylator phenotype.";
RL Elife 3:E02313-E02313(2014).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1048, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-99, SUMOYLATION [LARGE SCALE
RP ANALYSIS] AT LYS-759 (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [18]
RP STRUCTURE BY NMR OF 22-132.
RG Northeast structural genomics consortium (NESG);
RT "NMR solution structure of the N-terminal domain of human USP28.";
RL Submitted (JUL-2012) to the PDB data bank.
CC -!- FUNCTION: Deubiquitinase involved in DNA damage response checkpoint and
CC MYC proto-oncogene stability. Involved in DNA damage induced apoptosis
CC by specifically deubiquitinating proteins of the DNA damage pathway
CC such as CLSPN. Also involved in G2 DNA damage checkpoint, by
CC deubiquitinating CLSPN, and preventing its degradation by the anaphase
CC promoting complex/cyclosome (APC/C). In contrast, it does not
CC deubiquitinate PLK1. Specifically deubiquitinates MYC in the
CC nucleoplasm, leading to prevent MYC degradation by the proteasome: acts
CC by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the
CC nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7)
CC complex. In contrast, it does not interact with isoform 4 of FBXW7
CC (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining
CC the selective MYC degradation in the nucleolus. Deubiquitinates ZNF304,
CC hence preventing ZNF304 degradation by the proteasome and leading to
CC the activated KRAS-mediated promoter hypermethylation and
CC transcriptional silencing of tumor suppressor genes (TSGs) in a subset
CC of colorectal cancers (CRC) cells (PubMed:24623306).
CC {ECO:0000269|PubMed:16901786, ECO:0000269|PubMed:17558397,
CC ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:18662541,
CC ECO:0000269|PubMed:24623306}.
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;
CC -!- SUBUNIT: Interacts with ZNF304 (PubMed:24623306). Interacts with PRKD1
CC (PubMed:24623306). Interacts with TP53BP1 (PubMed:16901786). Interacts
CC with isoform 1 of FBXW7; following DNA damage, dissociates from FBXW7
CC leading to degradation of MYC (PubMed:17873522, PubMed:17558397).
CC {ECO:0000269|PubMed:16901786, ECO:0000269|PubMed:17558397,
CC ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:24623306}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:17558397}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96RU2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96RU2-2; Sequence=VSP_015580;
CC Name=3;
CC IsoId=Q96RU2-3; Sequence=VSP_057359, VSP_057360;
CC -!- INDUCTION: Down-regulated upon hypoxia (PubMed:20046830). Up-regulated
CC by the transcription factor c-Jun/JUN in a KRAS-dependent manner in
CC colorectal cancer (CRC) cells (PubMed:24623306).
CC {ECO:0000269|PubMed:20046830, ECO:0000269|PubMed:24623306}.
CC -!- PTM: Degraded upon nickel ion level or hypoxia exposure.
CC -!- PTM: Phosphorylated upon DNA damage at Ser-67 and Ser-714, by ATM or
CC ATR (PubMed:16901786). Phosphorylated by PRKD1 (PubMed:24623306).
CC {ECO:0000269|PubMed:16901786, ECO:0000269|PubMed:24623306}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP28 subfamily.
CC {ECO:0000305}.
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DR EMBL; AF266283; AAK58565.1; -; mRNA.
DR EMBL; EF445045; ACA06098.1; -; Genomic_DNA.
DR EMBL; EF445045; ACA06099.1; -; Genomic_DNA.
DR EMBL; AP001874; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003170; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455523; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF459544; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67232.1; -; Genomic_DNA.
DR EMBL; BC065928; AAH65928.1; -; mRNA.
DR EMBL; AB040948; BAA96039.1; -; mRNA.
DR CCDS; CCDS31680.1; -. [Q96RU2-1]
DR CCDS; CCDS86248.1; -. [Q96RU2-3]
DR RefSeq; NP_001333187.1; NM_001346258.1. [Q96RU2-2]
DR RefSeq; NP_001333202.1; NM_001346273.1. [Q96RU2-3]
DR RefSeq; NP_065937.1; NM_020886.3. [Q96RU2-1]
DR PDB; 2LVA; NMR; -; A=22-132.
DR PDB; 2MUU; NMR; -; A=1-120.
DR PDB; 6H4H; X-ray; 3.50 A; A/B=149-707.
DR PDB; 6H4I; X-ray; 3.22 A; A/C=148-707.
DR PDB; 6HEH; X-ray; 2.26 A; A=149-399, A=580-703.
DR PDB; 6HEI; X-ray; 1.64 A; A=149-399, A=580-703.
DR PDB; 6HEJ; X-ray; 2.79 A; A/B=149-703.
DR PDB; 6HEK; X-ray; 3.03 A; A/C=149-703.
DR PDBsum; 2LVA; -.
DR PDBsum; 2MUU; -.
DR PDBsum; 6H4H; -.
DR PDBsum; 6H4I; -.
DR PDBsum; 6HEH; -.
DR PDBsum; 6HEI; -.
DR PDBsum; 6HEJ; -.
DR PDBsum; 6HEK; -.
DR AlphaFoldDB; Q96RU2; -.
DR BMRB; Q96RU2; -.
DR SMR; Q96RU2; -.
DR BioGRID; 121683; 101.
DR IntAct; Q96RU2; 21.
DR MINT; Q96RU2; -.
DR STRING; 9606.ENSP00000003302; -.
DR BindingDB; Q96RU2; -.
DR ChEMBL; CHEMBL2157853; -.
DR MEROPS; C19.054; -.
DR GlyGen; Q96RU2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96RU2; -.
DR PhosphoSitePlus; Q96RU2; -.
DR BioMuta; USP28; -.
DR DMDM; 20140700; -.
DR EPD; Q96RU2; -.
DR jPOST; Q96RU2; -.
DR MassIVE; Q96RU2; -.
DR MaxQB; Q96RU2; -.
DR PaxDb; Q96RU2; -.
DR PeptideAtlas; Q96RU2; -.
DR PRIDE; Q96RU2; -.
DR ProteomicsDB; 66797; -.
DR ProteomicsDB; 78033; -. [Q96RU2-1]
DR ProteomicsDB; 78034; -. [Q96RU2-2]
DR Antibodypedia; 1708; 309 antibodies from 38 providers.
DR DNASU; 57646; -.
DR Ensembl; ENST00000003302.8; ENSP00000003302.4; ENSG00000048028.11. [Q96RU2-1]
DR Ensembl; ENST00000537706.5; ENSP00000445743.1; ENSG00000048028.11. [Q96RU2-3]
DR GeneID; 57646; -.
DR KEGG; hsa:57646; -.
DR UCSC; uc001poh.4; human. [Q96RU2-1]
DR CTD; 57646; -.
DR DisGeNET; 57646; -.
DR GeneCards; USP28; -.
DR HGNC; HGNC:12625; USP28.
DR HPA; ENSG00000048028; Tissue enhanced (heart muscle, skeletal muscle, tongue).
DR MIM; 610748; gene.
DR neXtProt; NX_Q96RU2; -.
DR OpenTargets; ENSG00000048028; -.
DR PharmGKB; PA37250; -.
DR VEuPathDB; HostDB:ENSG00000048028; -.
DR eggNOG; KOG1863; Eukaryota.
DR GeneTree; ENSGT00940000157670; -.
DR HOGENOM; CLU_467647_0_0_1; -.
DR InParanoid; Q96RU2; -.
DR OMA; DQQVLYK; -.
DR OrthoDB; 194025at2759; -.
DR PhylomeDB; Q96RU2; -.
DR TreeFam; TF329035; -.
DR PathwayCommons; Q96RU2; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SABIO-RK; Q96RU2; -.
DR SignaLink; Q96RU2; -.
DR SIGNOR; Q96RU2; -.
DR BioGRID-ORCS; 57646; 16 hits in 1130 CRISPR screens.
DR ChiTaRS; USP28; human.
DR GenomeRNAi; 57646; -.
DR Pharos; Q96RU2; Tchem.
DR PRO; PR:Q96RU2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96RU2; protein.
DR Bgee; ENSG00000048028; Expressed in gastrocnemius and 183 other tissues.
DR ExpressionAtlas; Q96RU2; baseline and differential.
DR Genevisible; Q96RU2; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00443; UCH; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; DNA damage; DNA repair; Hydrolase;
KW Isopeptide bond; Nucleus; Phosphoprotein; Protease; Reference proteome;
KW Thiol protease; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..1077
FT /note="Ubiquitin carboxyl-terminal hydrolase 28"
FT /id="PRO_0000080657"
FT DOMAIN 97..116
FT /note="UIM"
FT /evidence="ECO:0000305"
FT DOMAIN 162..650
FT /note="USP"
FT REGION 60..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 477..535
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 697..728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 477..528
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 702..728
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 171
FT /note="Nucleophile"
FT ACT_SITE 600
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16901786"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 550
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5I043"
FT MOD_RES 714
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16901786"
FT MOD_RES 1048
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CROSSLNK 99
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 583
FT /note="P -> E (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057359"
FT VAR_SEQ 584..1077
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057360"
FT VAR_SEQ 769..800
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10819331"
FT /id="VSP_015580"
FT MUTAGEN 171
FT /note="C->A: Abolishes deubiquitinase activity."
FT /evidence="ECO:0000269|PubMed:16901786,
FT ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:24623306"
FT MUTAGEN 899
FT /note="S->A: Prevents ZNF304 ubiquitination reduction."
FT /evidence="ECO:0000269|PubMed:24623306"
FT CONFLICT 289..303
FT /note="VQLFYGTFLTEGVRE -> IVIVMSFLKSLSLCL (in Ref. 4;
FT BAA96039)"
FT /evidence="ECO:0000305"
FT HELIX 7..9
FT /evidence="ECO:0007829|PDB:2MUU"
FT HELIX 23..32
FT /evidence="ECO:0007829|PDB:2LVA"
FT HELIX 37..46
FT /evidence="ECO:0007829|PDB:2LVA"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:2LVA"
FT HELIX 51..58
FT /evidence="ECO:0007829|PDB:2LVA"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:2LVA"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:2MUU"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:2MUU"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:2MUU"
FT HELIX 100..111
FT /evidence="ECO:0007829|PDB:2LVA"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:2LVA"
FT HELIX 151..154
FT /evidence="ECO:0007829|PDB:6HEH"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 171..181
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 184..191
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 197..201
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 206..227
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 236..242
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 256..278
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 287..292
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 294..302
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 305..319
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 326..333
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 353..358
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 361..368
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 370..373
FT /evidence="ECO:0007829|PDB:6HEI"
FT TURN 374..377
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 390..393
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 395..397
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 399..401
FT /evidence="ECO:0007829|PDB:6HEJ"
FT HELIX 402..430
FT /evidence="ECO:0007829|PDB:6HEJ"
FT STRAND 431..436
FT /evidence="ECO:0007829|PDB:6HEJ"
FT HELIX 441..452
FT /evidence="ECO:0007829|PDB:6HEJ"
FT HELIX 535..571
FT /evidence="ECO:0007829|PDB:6HEJ"
FT TURN 572..574
FT /evidence="ECO:0007829|PDB:6HEK"
FT HELIX 577..579
FT /evidence="ECO:0007829|PDB:6HEJ"
FT STRAND 583..595
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 598..607
FT /evidence="ECO:0007829|PDB:6HEI"
FT TURN 608..611
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 612..617
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 620..623
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 626..633
FT /evidence="ECO:0007829|PDB:6HEI"
FT STRAND 640..649
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 653..655
FT /evidence="ECO:0007829|PDB:6HEH"
FT HELIX 668..671
FT /evidence="ECO:0007829|PDB:6HEI"
FT HELIX 675..698
FT /evidence="ECO:0007829|PDB:6HEI"
FT CROSSLNK Q96RU2-2:759
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
SQ SEQUENCE 1077 AA; 122491 MW; 799C758888C67B82 CRC64;
MTAELQQDDA AGAADGHGSS CQMLLNQLRE ITGIQDPSFL HEALKASNGD ITQAVSLLTD
ERVKEPSQDT VATEPSEVEG SAANKEVLAK VIDLTHDNKD DLQAAIALSL LESPKIQADG
RDLNRMHEAT SAETKRSKRK RCEVWGENPN PNDWRRVDGW PVGLKNVGNT CWFSAVIQSL
FQLPEFRRLV LSYSLPQNVL ENCRSHTEKR NIMFMQELQY LFALMMGSNR KFVDPSAALD
LLKGAFRSSE EQQQDVSEFT HKLLDWLEDA FQLAVNVNSP RNKSENPMVQ LFYGTFLTEG
VREGKPFCNN ETFGQYPLQV NGYRNLDECL EGAMVEGDVE LLPSDHSVKY GQERWFTKLP
PVLTFELSRF EFNQSLGQPE KIHNKLEFPQ IIYMDRYMYR SKELIRNKRE CIRKLKEEIK
ILQQKLERYV KYGSGPARFP LPDMLKYVIE FASTKPASES CPPESDTHMT LPLSSVHCSV
SDQTSKESTS TESSSQDVES TFSSPEDSLP KSKPLTSSRS SMEMPSQPAP RTVTDEEINF
VKTCLQRWRS EIEQDIQDLK TCIASTTQTI EQMYCDPLLR QVPYRLHAVL VHEGQANAGH
YWAYIYNQPR QSWLKYNDIS VTESSWEEVE RDSYGGLRNV SAYCLMYIND KLPYFNAEAA
PTESDQMSEV EALSVELKHY IQEDNWRFEQ EVEEWEEEQS CKIPQMESST NSSSQDYSTS
QEPSVASSHG VRCLSSEHAV IVKEQTAQAI ANTARAYEKS GVEAALSEVM LSPAMQGVIL
AIAKARQTFD RDGSEAGLIK AFHEEYSRLY QLAKETPTSH SDPRLQHVLV YFFQNEAPKR
VVERTLLEQF ADKNLSYDER SISIMKVAQA KLKEIGPDDM NMEEYKKWHE DYSLFRKVSV
YLLTGLELYQ KGKYQEALSY LVYAYQSNAA LLMKGPRRGV KESVIALYRR KCLLELNAKA
ASLFETNDDH SVTEGINVMN ELIIPCIHLI INNDISKDDL DAIEVMRNHW CSYLGQDIAE
NLQLCLGEFL PRLLDPSAEI IVLKEPPTIR PNSPYDLCSR FAAVMESIQG VSTVTVK
