UBP25_HUMAN
ID UBP25_HUMAN Reviewed; 1055 AA.
AC Q9UHP3; C0LSZ0; Q6DHZ9; Q9H9W1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 4.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 25;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 25;
DE AltName: Full=USP on chromosome 21;
DE AltName: Full=Ubiquitin thioesterase 25;
DE AltName: Full=Ubiquitin-specific-processing protease 25;
GN Name=USP25; Synonyms=USP21;
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] (ISOFORMS USP25A AND USP25B), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=10644437; DOI=10.1006/geno.1999.6025;
RA Valero R., Marfany G., Gonzalez-Angulo O., Gonzalez-Gonzalez G.,
RA Puelles L., Gonzalez-Duarte R.;
RT "USP25, a novel gene encoding a deubiquitinating enzyme, is located in the
RT gene-poor region 21q11.2.";
RL Genomics 62:395-405(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM USP25A), AND FUNCTION.
RX PubMed=10612803;
RX DOI=10.1002/(sici)1098-2264(200002)27:2<153::aid-gcc6>3.0.co;2-a;
RA Groet J., Ives J.H., Jones T.A., Danton M., Flomen R.H., Sheer D.,
RA Hrascan R., Pavelic K., Nizetic D.;
RT "Narrowing of the region of allelic loss in 21q11-21 in squamous non-small
RT cell lung carcinoma and cloning of a novel ubiquitin-specific protease gene
RT from the deleted segment.";
RL Genes Chromosomes Cancer 27:153-161(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM USP25M).
RA Valero R., Bosch-Comas A., Denuc A., Gonzalez-Duarte R., Marfany G.;
RL Submitted (FEB-2009) to the EMBL/GenBank/DDBJ databases.
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM USP25A).
RC TISSUE=Placenta;
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 319-1055 (ISOFORM USP25A).
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 [7]
RP ALTERNATIVE SPLICING, FUNCTION, AND TISSUE SPECIFICITY.
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 [8]
RP ALTERNATIVE SPLICING, INTERACTION WITH ACTA1; FLNC; GAPDH AND MYBPC1,
RP INDUCTION, SUBCELLULAR LOCATION, AND POSSIBLE FUNCTION.
RX PubMed=16501887; DOI=10.1007/s00018-005-5533-1;
RA Bosch-Comas A., Lindsten K., Gonzalez-Duarte R., Masucci M.G., Marfany G.;
RT "The ubiquitin-specific protease USP25 interacts with three sarcomeric
RT proteins.";
RL Cell. Mol. Life Sci. 63:723-734(2006).
RN [9]
RP SUMOYLATION AT LYS-99, FUNCTION, INTERACTION WITH SUMO1; SUMO3 AND
RP UBIQUITIN, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF VAL-91;
RP ILE-92 AND LYS-99.
RX PubMed=18538659; DOI=10.1016/j.molcel.2008.03.021;
RA Meulmeester E., Kunze M., Hsiao H.H., Urlaub H., Melchior F.;
RT "Mechanism and consequences for paralog-specific sumoylation of ubiquitin-
RT specific protease 25.";
RL Mol. Cell 30:610-619(2008).
RN [10]
RP UBIQUITINATION AT LYS-99, DEUBIQUITINATION, ACTIVE SITE CYS-178,
RP ACETYLATION, PHOSPHORYLATION, SUMOYLATION, FUNCTION, SUBCELLULAR LOCATION,
RP SUBUNIT, AND MUTAGENESIS OF LYS-99 AND CYS-178.
RX PubMed=19440361; DOI=10.1371/journal.pone.0005571;
RA Denuc A., Bosch-Comas A., Gonzalez-Duarte R., Marfany G.;
RT "The UBA-UIM domains of the USP25 regulate the enzyme ubiquitination state
RT and modulate substrate recognition.";
RL PLoS ONE 4:E5571-E5571(2009).
RN [11]
RP INTERACTION WITH SYK, PHOSPHORYLATION AT TYR-740, AND MUTAGENESIS OF
RP TYR-740; THR-878; TYR-880 AND ILE-883.
RX PubMed=19909739; DOI=10.1016/j.yexcr.2009.10.023;
RA Cholay M., Reverdy C., Benarous R., Colland F., Daviet L.;
RT "Functional interaction between the ubiquitin-specific protease 25 and the
RT SYK tyrosine kinase.";
RL Exp. Cell Res. 316:667-675(2010).
RN [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: Deubiquitinating enzyme that hydrolyzes ubiquitin moieties
CC conjugated to substrates and thus, functions to process newly
CC synthesized Ubiquitin, to recycle ubiquitin molecules or to edit
CC polyubiquitin chains and prevents proteasomal degradation of
CC substrates. Hydrolyzes both 'Lys-48'- and 'Lys-63'-linked
CC tetraubiquitin chains.
CC -!- FUNCTION: The muscle-specific isoform (USP25m) may have a role in the
CC regulation of muscular differentiation and function.
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: Homodimer or oligomer. Interacts with ACTA1 (via its C-
CC terminus); the interaction occurs for all isoforms but is strongest for
CC isoform USP25m in muscle differentiating cells. Interacts (isoform
CC USP25m only) with MYBPC1; the interaction prevents proteasomal
CC degradation of MYBPC1. Interacts (isoform USP25m only) with FLNC (via
CC filament repeats 17-18, 20-21 and 24). Interacts with GAPDH. Interacts
CC with SUMO3; the interaction sumoylates efficiently USP25. Interacts
CC with SUMO2; the interaction sumoylates efficiently USP25. Interacts
CC with SUMO1; the interaction only weakly sumoylates USP25. Interacts
CC with SYK; phosphorylates USP25 and regulates USP25 intracellular
CC levels. {ECO:0000269|PubMed:16501887, ECO:0000269|PubMed:18538659,
CC ECO:0000269|PubMed:19440361, ECO:0000269|PubMed:19909739}.
CC -!- INTERACTION:
CC Q9UHP3; O15481: MAGEB4; NbExp=3; IntAct=EBI-2513462, EBI-751857;
CC Q9UHP3; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-2513462, EBI-10172526;
CC Q9UHP3; P17612: PRKACA; NbExp=3; IntAct=EBI-2513462, EBI-476586;
CC Q9UHP3; Q3MIT2: PUS10; NbExp=3; IntAct=EBI-2513462, EBI-11983583;
CC Q9UHP3; P54725: RAD23A; NbExp=12; IntAct=EBI-2513462, EBI-746453;
CC Q9UHP3; P54727: RAD23B; NbExp=4; IntAct=EBI-2513462, EBI-954531;
CC Q9UHP3; P61956: SUMO2; NbExp=6; IntAct=EBI-2513462, EBI-473220;
CC Q9UHP3; P43405: SYK; NbExp=8; IntAct=EBI-2513462, EBI-78302;
CC Q9UHP3; P37173: TGFBR2; NbExp=3; IntAct=EBI-2513462, EBI-296151;
CC Q9UHP3; Q9BTV4: TMEM43; NbExp=3; IntAct=EBI-2513462, EBI-721293;
CC Q9UHP3; Q9BUY5: ZNF426; NbExp=3; IntAct=EBI-2513462, EBI-743265;
CC Q9UHP3; PRO_0000449633 [P0DTD1]: rep; Xeno; NbExp=6; IntAct=EBI-2513462, EBI-25492395;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16501887,
CC ECO:0000269|PubMed:19440361}.
CC -!- SUBCELLULAR LOCATION: [Isoform USP25m]: Cytoplasm {ECO:0000250}.
CC Nucleus {ECO:0000250}. Note=Some transient punctuate nuclear location
CC in myotubes during myocyte development. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=USP25a;
CC IsoId=Q9UHP3-2; Sequence=Displayed;
CC Name=USP25b;
CC IsoId=Q9UHP3-1; Sequence=VSP_039632;
CC Name=USP25m; Synonyms=Muscle-specific isoform;
CC IsoId=Q9UHP3-3; Sequence=VSP_039631;
CC -!- TISSUE SPECIFICITY: Isoform USP25a is found in most adult and fetal
CC tissues; expression is moderately high in testis, pancreas, kidney,
CC skeletal muscle, liver, lung, placenta, brain, heart, but very low in
CC peripheral blood, colon, small intestine, ovary, prostate, thymus and
CC spleen. Isoform USP25b is found in all tissues except heart and
CC skeletal muscle. Isoform USP25m is heart and skeletal muscle specific.
CC {ECO:0000269|PubMed:10644437, ECO:0000269|PubMed:11597335}.
CC -!- INDUCTION: The muscle-specific isoform (USP25m) is up-regulated during
CC myocyte differentiation. Levels increase up to 100-fold towards
CC completion of differentiation. {ECO:0000269|PubMed:16501887}.
CC -!- PTM: Acetylated. {ECO:0000269|PubMed:19440361}.
CC -!- PTM: Sumoylation impairs binding to and hydrolysis of ubiquitin chains.
CC Sumoylated preferentially with SUMO2 or SUMO3. Desumoylated by SENP1.
CC Regulated by ubiquitination on the same residue.
CC {ECO:0000269|PubMed:19440361}.
CC -!- PTM: Preferentially monoubiquitinated but can also be
CC polyubiquitinated. Autodeubiquitinated. Ubiquitination activates the
CC enzymatic activity either by preventing sumoylation or by allowing
CC novel interactions. {ECO:0000269|PubMed:19440361}.
CC -!- PTM: Phosphorylation in the C-terminal by SYK regulates USP25 cellular
CC levels. {ECO:0000269|PubMed:19440361, ECO:0000269|PubMed:19909739}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; AF170562; AAF32263.1; -; mRNA.
DR EMBL; AF134213; AAF24998.1; -; mRNA.
DR EMBL; FJ763652; ACN76567.1; -; mRNA.
DR EMBL; CH471079; EAX10041.1; -; Genomic_DNA.
DR EMBL; BC075792; AAH75792.1; -; mRNA.
DR EMBL; AK022574; BAB14107.1; -; mRNA.
DR CCDS; CCDS33515.1; -. [Q9UHP3-2]
DR CCDS; CCDS63336.1; -. [Q9UHP3-3]
DR CCDS; CCDS63337.1; -. [Q9UHP3-1]
DR RefSeq; NP_001269970.1; NM_001283041.1. [Q9UHP3-3]
DR RefSeq; NP_001269971.1; NM_001283042.1. [Q9UHP3-1]
DR RefSeq; NP_037528.3; NM_013396.4. [Q9UHP3-2]
DR PDB; 2MUX; NMR; -; A=1-146.
DR PDB; 5GP7; X-ray; 1.50 A; B=1046-1055.
DR PDB; 5O71; X-ray; 3.28 A; A=1-714.
DR PDB; 6H4J; X-ray; 3.07 A; A/B=157-706.
DR PDB; 6H4K; X-ray; 2.05 A; A=765-1055.
DR PDB; 6HEL; X-ray; 2.94 A; A/B=157-714.
DR PDB; 6HEM; X-ray; 1.72 A; A=748-1048.
DR PDBsum; 2MUX; -.
DR PDBsum; 5GP7; -.
DR PDBsum; 5O71; -.
DR PDBsum; 6H4J; -.
DR PDBsum; 6H4K; -.
DR PDBsum; 6HEL; -.
DR PDBsum; 6HEM; -.
DR AlphaFoldDB; Q9UHP3; -.
DR BMRB; Q9UHP3; -.
DR SMR; Q9UHP3; -.
DR BioGRID; 118895; 82.
DR IntAct; Q9UHP3; 38.
DR MINT; Q9UHP3; -.
DR STRING; 9606.ENSP00000383044; -.
DR BindingDB; Q9UHP3; -.
DR ChEMBL; CHEMBL4295975; -.
DR MEROPS; C19.041; -.
DR iPTMnet; Q9UHP3; -.
DR PhosphoSitePlus; Q9UHP3; -.
DR BioMuta; USP25; -.
DR DMDM; 302393833; -.
DR EPD; Q9UHP3; -.
DR jPOST; Q9UHP3; -.
DR MassIVE; Q9UHP3; -.
DR MaxQB; Q9UHP3; -.
DR PaxDb; Q9UHP3; -.
DR PeptideAtlas; Q9UHP3; -.
DR PRIDE; Q9UHP3; -.
DR ProteomicsDB; 84385; -. [Q9UHP3-2]
DR ProteomicsDB; 84386; -. [Q9UHP3-1]
DR ProteomicsDB; 84387; -. [Q9UHP3-3]
DR Antibodypedia; 5805; 263 antibodies from 30 providers.
DR DNASU; 29761; -.
DR Ensembl; ENST00000285679.10; ENSP00000285679.6; ENSG00000155313.16. [Q9UHP3-2]
DR Ensembl; ENST00000285681.6; ENSP00000285681.2; ENSG00000155313.16. [Q9UHP3-1]
DR Ensembl; ENST00000400183.7; ENSP00000383044.2; ENSG00000155313.16. [Q9UHP3-3]
DR GeneID; 29761; -.
DR KEGG; hsa:29761; -.
DR MANE-Select; ENST00000400183.7; ENSP00000383044.2; NM_001283041.3; NP_001269970.1. [Q9UHP3-3]
DR UCSC; uc002yjy.3; human. [Q9UHP3-2]
DR CTD; 29761; -.
DR DisGeNET; 29761; -.
DR GeneCards; USP25; -.
DR HGNC; HGNC:12624; USP25.
DR HPA; ENSG00000155313; Tissue enhanced (skeletal).
DR MIM; 604736; gene.
DR neXtProt; NX_Q9UHP3; -.
DR OpenTargets; ENSG00000155313; -.
DR PharmGKB; PA37249; -.
DR VEuPathDB; HostDB:ENSG00000155313; -.
DR eggNOG; KOG1863; Eukaryota.
DR GeneTree; ENSGT00940000157962; -.
DR HOGENOM; CLU_012188_0_0_1; -.
DR InParanoid; Q9UHP3; -.
DR OMA; KGFNEPP; -.
DR OrthoDB; 194025at2759; -.
DR PhylomeDB; Q9UHP3; -.
DR TreeFam; TF329035; -.
DR PathwayCommons; Q9UHP3; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR SignaLink; Q9UHP3; -.
DR BioGRID-ORCS; 29761; 11 hits in 1128 CRISPR screens.
DR ChiTaRS; USP25; human.
DR GenomeRNAi; 29761; -.
DR Pharos; Q9UHP3; Tchem.
DR PRO; PR:Q9UHP3; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q9UHP3; protein.
DR Bgee; ENSG00000155313; Expressed in sperm and 198 other tissues.
DR ExpressionAtlas; Q9UHP3; baseline and differential.
DR Genevisible; Q9UHP3; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0051117; F:ATPase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IMP:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008233; F:peptidase activity; TAS:ProtInc.
DR GO; GO:0032183; F:SUMO binding; IPI:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; NAS:ParkinsonsUK-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0019783; F:ubiquitin-like protein peptidase activity; NAS:ParkinsonsUK-UCL.
DR GO; GO:1904293; P:negative regulation of ERAD pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0016579; P:protein deubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IMP:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IMP:UniProtKB.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
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; IPR003903; UIM_dom.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02809; UIM; 2.
DR SMART; SM00726; UIM; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50330; UIM; 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; Coiled coil; Cytoplasm; Hydrolase;
KW Isopeptide bond; Nucleus; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Thiol protease; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..1055
FT /note="Ubiquitin carboxyl-terminal hydrolase 25"
FT /id="PRO_0000080653"
FT DOMAIN 14..57
FT /note="UBA-like"
FT DOMAIN 97..116
FT /note="UIM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 123..140
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 169..657
FT /note="USP"
FT REGION 77..102
FT /note="SUMO interaction domain (SIM)"
FT REGION 464..507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 727..749
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 541..578
FT /evidence="ECO:0000255"
FT COILED 684..717
FT /evidence="ECO:0000255"
FT MOTIF 89..95
FT /note="Required for SUMO paralog-specific binding"
FT COMPBIAS 472..507
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 178
FT /evidence="ECO:0000269|PubMed:19440361"
FT ACT_SITE 599
FT /evidence="ECO:0000250"
FT ACT_SITE 607
FT /evidence="ECO:0000250"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 740
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:19909739"
FT CROSSLNK 99
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT CROSSLNK 99
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:19440361"
FT VAR_SEQ 779
FT /note="S -> SIMMTPNMQGIIMAIGKSRSVYDRCGPEAGFFK (in isoform
FT USP25b)"
FT /evidence="ECO:0000303|PubMed:10644437"
FT /id="VSP_039632"
FT VAR_SEQ 779
FT /note="S -> SKPENTTSQPLSNQRVVEVAIPHVGKFMIESKEGGYDDEIMMTPNMQ
FT GIIMAIGKSRSVYDRCGPEAGFFK (in isoform USP25m)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_039631"
FT MUTAGEN 91
FT /note="V->A: No interaction with SUMO3; when associated
FT with A-92."
FT /evidence="ECO:0000269|PubMed:18538659"
FT MUTAGEN 92
FT /note="I->A: No interaction with SUMO3; when associated
FT with A-91."
FT /evidence="ECO:0000269|PubMed:18538659"
FT MUTAGEN 99
FT /note="K->R: Abolishes sumoylation. Decreased enzymatic
FT activity."
FT /evidence="ECO:0000269|PubMed:18538659,
FT ECO:0000269|PubMed:19440361"
FT MUTAGEN 178
FT /note="C->S: Abrogates deubiquitinating activity. No effect
FT on homo- or oligomerization."
FT /evidence="ECO:0000269|PubMed:19440361"
FT MUTAGEN 740
FT /note="Y->F: No effect on interaction with SYK."
FT /evidence="ECO:0000269|PubMed:19909739"
FT MUTAGEN 878
FT /note="T->I: No effect on interaction with SYK."
FT /evidence="ECO:0000269|PubMed:19909739"
FT MUTAGEN 880
FT /note="Y->F: No effect on interaction with SYK."
FT /evidence="ECO:0000269|PubMed:19909739"
FT MUTAGEN 883
FT /note="I->S: No effect on interaction with SYK."
FT /evidence="ECO:0000269|PubMed:19909739"
FT CONFLICT 544
FT /note="E -> K (in Ref. 1; AAF32263 and 3; ACN76567)"
FT /evidence="ECO:0000305"
FT HELIX 12..27
FT /evidence="ECO:0007829|PDB:2MUX"
FT HELIX 33..43
FT /evidence="ECO:0007829|PDB:2MUX"
FT HELIX 47..55
FT /evidence="ECO:0007829|PDB:2MUX"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:2MUX"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:2MUX"
FT HELIX 100..116
FT /evidence="ECO:0007829|PDB:2MUX"
FT HELIX 125..136
FT /evidence="ECO:0007829|PDB:2MUX"
FT TURN 158..161
FT /evidence="ECO:0007829|PDB:6H4J"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:5O71"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:6H4J"
FT HELIX 178..189
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 191..198
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 218..234
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 237..240
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 243..248
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 263..279
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:5O71"
FT HELIX 294..299
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 321..326
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 333..342
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 348..350
FT /evidence="ECO:0007829|PDB:6H4J"
FT TURN 351..355
FT /evidence="ECO:0007829|PDB:6H4J"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 368..375
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:6HEL"
FT TURN 381..384
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 385..388
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 397..400
FT /evidence="ECO:0007829|PDB:6HEL"
FT TURN 402..404
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 409..437
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 441..444
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 448..460
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 542..579
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 584..586
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 590..601
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 603..614
FT /evidence="ECO:0007829|PDB:6HEL"
FT TURN 615..618
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 619..624
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 627..629
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 633..640
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 641..644
FT /evidence="ECO:0007829|PDB:6HEL"
FT STRAND 648..658
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 660..662
FT /evidence="ECO:0007829|PDB:6HEL"
FT TURN 669..671
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 677..680
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 683..700
FT /evidence="ECO:0007829|PDB:6HEL"
FT HELIX 751..765
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 773..793
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 802..804
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 807..813
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 818..829
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 832..834
FT /evidence="ECO:0007829|PDB:6HEM"
FT STRAND 835..837
FT /evidence="ECO:0007829|PDB:6HEM"
FT TURN 838..840
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 841..853
FT /evidence="ECO:0007829|PDB:6HEM"
FT TURN 856..858
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 861..889
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 893..913
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 921..943
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 948..960
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 962..965
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 966..970
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 976..990
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 991..994
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 999..1013
FT /evidence="ECO:0007829|PDB:6HEM"
FT HELIX 1033..1044
FT /evidence="ECO:0007829|PDB:6HEM"
SQ SEQUENCE 1055 AA; 122218 MW; 0B9CECDCAD619CF2 CRC64;
MTVEQNVLQQ SAAQKHQQTF LNQLREITGI NDTQILQQAL KDSNGNLELA VAFLTAKNAK
TPQQEETTYY QTALPGNDRY ISVGSQADTN VIDLTGDDKD DLQRAIALSL AESNRAFRET
GITDEEQAIS RVLEASIAEN KACLKRTPTE VWRDSRNPYD RKRQDKAPVG LKNVGNTCWF
SAVIQSLFNL LEFRRLVLNY KPPSNAQDLP RNQKEHRNLP FMRELRYLFA LLVGTKRKYV
DPSRAVEILK DAFKSNDSQQ QDVSEFTHKL LDWLEDAFQM KAEEETDEEK PKNPMVELFY
GRFLAVGVLE GKKFENTEMF GQYPLQVNGF KDLHECLEAA MIEGEIESLH SENSGKSGQE
HWFTELPPVL TFELSRFEFN QALGRPEKIH NKLEFPQVLY LDRYMHRNRE ITRIKREEIK
RLKDYLTVLQ QRLERYLSYG SGPKRFPLVD VLQYALEFAS SKPVCTSPVD DIDASSPPSG
SIPSQTLPST TEQQGALSSE LPSTSPSSVA AISSRSVIHK PFTQSRIPPD LPMHPAPRHI
TEEELSVLES CLHRWRTEIE NDTRDLQESI SRIHRTIELM YSDKSMIQVP YRLHAVLVHE
GQANAGHYWA YIFDHRESRW MKYNDIAVTK SSWEELVRDS FGGYRNASAY CLMYINDKAQ
FLIQEEFNKE TGQPLVGIET LPPDLRDFVE EDNQRFEKEL EEWDAQLAQK ALQEKLLASQ
KLRESETSVT TAQAAGDPEY LEQPSRSDFS KHLKEETIQI ITKASHEHED KSPETVLQSA
IKLEYARLVK LAQEDTPPET DYRLHHVVVY FIQNQAPKKI IEKTLLEQFG DRNLSFDERC
HNIMKVAQAK LEMIKPEEVN LEEYEEWHQD YRKFRETTMY LIIGLENFQR ESYIDSLLFL
ICAYQNNKEL LSKGLYRGHD EELISHYRRE CLLKLNEQAA ELFESGEDRE VNNGLIIMNE
FIVPFLPLLL VDEMEEKDIL AVEDMRNRWC SYLGQEMEPH LQEKLTDFLP KLLDCSMEIK
SFHEPPKLPS YSTHELCERF ARIMLSLSRT PADGR
