UBP33_HUMAN
ID UBP33_HUMAN Reviewed; 942 AA.
AC Q8TEY7; Q8TEY6; Q96AV6; Q9H9F0; Q9UPQ5;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 33;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 33;
DE AltName: Full=Ubiquitin thioesterase 33;
DE AltName: Full=Ubiquitin-specific-processing protease 33;
DE AltName: Full=VHL-interacting deubiquitinating enzyme 1;
DE Short=hVDU1;
GN Name=USP33; Synonyms=KIAA1097, VDU1;
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 1 AND 2), UBIQUITINATION, INTERACTION
RP WITH VHL, AND TISSUE SPECIFICITY.
RX PubMed=11739384; DOI=10.1074/jbc.m108269200;
RA Li Z., Na X., Wang D., Schoen S.R., Messing E.M., Wu G.;
RT "Ubiquitination of a novel deubiquitinating enzyme requires direct binding
RT to von Hippel-Lindau tumor suppressor protein.";
RL J. Biol. Chem. 277:4656-4662(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 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 [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 FUNCTION, AND INTERACTION WITH DIO2.
RX PubMed=12865408; DOI=10.1172/jci200318348;
RA Curcio-Morelli C., Zavacki A.M., Christofollete M., Gereben B.,
RA de Freitas B.C., Harney J.W., Li Z., Wu G., Bianco A.C.;
RT "Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau
RT protein-interacting deubiquitinating enzymes regulates thyroid hormone
RT activation.";
RL J. Clin. Invest. 112:189-196(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP INTERACTION WITH SELENBP1, AND SUBCELLULAR LOCATION.
RX PubMed=19118533; DOI=10.1016/j.bbrc.2008.12.110;
RA Jeong J.Y., Wang Y., Sytkowski A.J.;
RT "Human selenium binding protein-1 (hSP56) interacts with VDU1 in a
RT selenium-dependent manner.";
RL Biochem. Biophys. Res. Commun. 379:583-588(2009).
RN [9]
RP FUNCTION, INTERACTION WITH ADRB2, AND MUTAGENESIS OF CYS-194 AND HIS-673.
RX PubMed=19424180; DOI=10.1038/emboj.2009.128;
RA Berthouze M., Venkataramanan V., Li Y., Shenoy S.K.;
RT "The deubiquitinases USP33 and USP20 coordinate beta2 adrenergic receptor
RT recycling and resensitization.";
RL EMBO J. 28:1684-1696(2009).
RN [10]
RP FUNCTION, INTERACTION WITH ARRB1 AND ARRB2, AND MUTAGENESIS OF CYS-194 AND
RP HIS-673.
RX PubMed=19363159; DOI=10.1073/pnas.0901083106;
RA Shenoy S.K., Modi A.S., Shukla A.K., Xiao K., Berthouze M., Ahn S.,
RA Wilkinson K.D., Miller W.E., Lefkowitz R.J.;
RT "Beta-arrestin-dependent signaling and trafficking of 7-transmembrane
RT receptors is reciprocally regulated by the deubiquitinase USP33 and the E3
RT ligase Mdm2.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:6650-6655(2009).
RN [11]
RP ALTERNATIVE SPLICING (ISOFORM 3), AND SUBCELLULAR LOCATION.
RX PubMed=21801292; DOI=10.1111/j.1600-0854.2011.01261.x;
RA Thorne C., Eccles R.L., Coulson J.M., Urbe S., Clague M.J.;
RT "Isoform-specific localization of the deubiquitinase USP33 to the Golgi
RT apparatus.";
RL Traffic 12:1563-1574(2011).
RN [12]
RP INTERACTION WITH ADRB2.
RX PubMed=23166351; DOI=10.1083/jcb.201208192;
RA Han S.O., Xiao K., Kim J., Wu J.H., Wisler J.W., Nakamura N.,
RA Freedman N.J., Shenoy S.K.;
RT "MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound
RT beta(2)-adrenergic receptors.";
RL J. Cell Biol. 199:817-830(2012).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CCP110, DEVELOPMENTAL
RP STAGE, AND MUTAGENESIS OF CYS-194 AND HIS-673.
RX PubMed=23486064; DOI=10.1038/nature11941;
RA Li J., D'Angiolella V., Seeley E.S., Kim S., Kobayashi T., Fu W.,
RA Campos E.I., Pagano M., Dynlacht B.D.;
RT "USP33 regulates centrosome biogenesis via deubiquitination of the
RT centriolar protein CP110.";
RL Nature 495:255-259(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, 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 [15]
RP STRUCTURE BY NMR OF 36-130, ZINC-BINDING, AND DOMAIN UBP-TYPE ZINC FINGER.
RX PubMed=17766394; DOI=10.1110/ps.072967807;
RA Allen M.D., Bycroft M.;
RT "The solution structure of the ZnF UBP domain of USP33/VDU1.";
RL Protein Sci. 16:2072-2075(2007).
CC -!- FUNCTION: Deubiquitinating enzyme involved in various processes such as
CC centrosome duplication, cellular migration and beta-2 adrenergic
CC receptor/ADRB2 recycling. Involved in regulation of centrosome
CC duplication by mediating deubiquitination of CCP110 in S and G2/M
CC phase, leading to stabilize CCP110 during the period which centrioles
CC duplicate and elongate. Involved in cell migration via its interaction
CC with intracellular domain of ROBO1, leading to regulate the Slit
CC signaling. Plays a role in commissural axon guidance cross the ventral
CC midline of the neural tube in a Slit-dependent manner, possibly by
CC mediating the deubiquitination of ROBO1. Acts as a regulator of G-
CC protein coupled receptor (GPCR) signaling by mediating the
CC deubiquitination of beta-arrestins (ARRB1 and ARRB2) and beta-2
CC adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling
CC and resensitization after prolonged agonist stimulation by
CC constitutively binding ADRB2, mediating deubiquitination of ADRB2 and
CC inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is
CC probably transferred to the translocated beta-arrestins, leading to
CC beta-arrestins deubiquitination and disengagement from ADRB2. This
CC suggests the existence of a dynamic exchange between the ADRB2 and
CC beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid
CC hormone regulation. Mediates deubiquitination of both 'Lys-48'- and
CC 'Lys-63'-linked polyubiquitin chains. {ECO:0000269|PubMed:12865408,
CC ECO:0000269|PubMed:19363159, ECO:0000269|PubMed:19424180,
CC ECO:0000269|PubMed:23486064}.
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 VHL, leading to its ubiquitination and
CC subsequent degradation (PubMed:11739384). Interacts with ARRB1 and
CC ARRB2 (PubMed:19363159). Interacts with ADRB2 (PubMed:19424180).
CC Interacts with DIO2 (PubMed:12865408). Interacts with ROBO1. Interacts
CC with SELENBP1; in a selenium-dependent manner (PubMed:19118533).
CC Interacts with CCP110 (PubMed:23486064). Interacts with ADRB2
CC (PubMed:23166351). {ECO:0000269|PubMed:11739384,
CC ECO:0000269|PubMed:12865408, ECO:0000269|PubMed:19118533,
CC ECO:0000269|PubMed:19363159, ECO:0000269|PubMed:19424180,
CC ECO:0000269|PubMed:23166351, ECO:0000269|PubMed:23486064}.
CC -!- INTERACTION:
CC Q8TEY7-2; Q13228: SELENBP1; NbExp=5; IntAct=EBI-719307, EBI-711619;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:19118533}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:23486064}.
CC Note=Associates with centrosomes predominantly in S and G2 phases but
CC less in G1 phase (PubMed:23486064). {ECO:0000269|PubMed:23486064}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Golgi apparatus
CC {ECO:0000269|PubMed:21801292}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8TEY7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TEY7-2; Sequence=VSP_008591;
CC Name=3;
CC IsoId=Q8TEY7-3; Sequence=VSP_008592, VSP_008593, VSP_008594;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:11739384}.
CC -!- DEVELOPMENTAL STAGE: Increased expression in S and early G2 phases and
CC lower levels in late G2 and M phases. {ECO:0000269|PubMed:23486064}.
CC -!- DOMAIN: The UBP-type zinc finger binds 3 zinc ions. However, it does
CC not bind ubiquitin, probably because the conserved Arg in position 86
CC is replaced by a Glu residue. {ECO:0000269|PubMed:17766394}.
CC -!- PTM: Ubiquitinated via a VHL-dependent pathway for proteasomal
CC degradation. {ECO:0000269|PubMed:11739384}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. USP20/USP33 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA83049.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF383172; AAL78314.1; -; mRNA.
DR EMBL; AF383173; AAL78315.1; -; mRNA.
DR EMBL; AB029020; BAA83049.1; ALT_INIT; mRNA.
DR EMBL; AK022864; BAB14279.1; -; mRNA.
DR EMBL; AC114487; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016663; AAH16663.1; -; mRNA.
DR CCDS; CCDS678.1; -. [Q8TEY7-1]
DR CCDS; CCDS679.1; -. [Q8TEY7-2]
DR CCDS; CCDS680.1; -. [Q8TEY7-3]
DR RefSeq; NP_055832.3; NM_015017.4. [Q8TEY7-1]
DR RefSeq; NP_963918.1; NM_201624.2. [Q8TEY7-2]
DR RefSeq; NP_963920.1; NM_201626.2. [Q8TEY7-3]
DR PDB; 2UZG; NMR; -; A=36-130.
DR PDBsum; 2UZG; -.
DR AlphaFoldDB; Q8TEY7; -.
DR SMR; Q8TEY7; -.
DR BioGRID; 116671; 128.
DR CORUM; Q8TEY7; -.
DR DIP; DIP-48942N; -.
DR IntAct; Q8TEY7; 29.
DR MINT; Q8TEY7; -.
DR STRING; 9606.ENSP00000359829; -.
DR MEROPS; C19.037; -.
DR iPTMnet; Q8TEY7; -.
DR PhosphoSitePlus; Q8TEY7; -.
DR BioMuta; USP33; -.
DR DMDM; 116242838; -.
DR EPD; Q8TEY7; -.
DR jPOST; Q8TEY7; -.
DR MassIVE; Q8TEY7; -.
DR MaxQB; Q8TEY7; -.
DR PaxDb; Q8TEY7; -.
DR PeptideAtlas; Q8TEY7; -.
DR PRIDE; Q8TEY7; -.
DR ProteomicsDB; 74526; -. [Q8TEY7-1]
DR ProteomicsDB; 74527; -. [Q8TEY7-2]
DR ProteomicsDB; 74528; -. [Q8TEY7-3]
DR Antibodypedia; 33489; 292 antibodies from 31 providers.
DR DNASU; 23032; -.
DR Ensembl; ENST00000357428.5; ENSP00000350009.1; ENSG00000077254.14. [Q8TEY7-1]
DR Ensembl; ENST00000370792.7; ENSP00000359828.3; ENSG00000077254.14. [Q8TEY7-3]
DR Ensembl; ENST00000370793.5; ENSP00000359829.1; ENSG00000077254.14. [Q8TEY7-1]
DR Ensembl; ENST00000370794.7; ENSP00000359830.3; ENSG00000077254.14. [Q8TEY7-2]
DR GeneID; 23032; -.
DR KEGG; hsa:23032; -.
DR MANE-Select; ENST00000370794.7; ENSP00000359830.3; NM_201624.3; NP_963918.1. [Q8TEY7-2]
DR UCSC; uc001dht.5; human. [Q8TEY7-1]
DR CTD; 23032; -.
DR DisGeNET; 23032; -.
DR GeneCards; USP33; -.
DR HGNC; HGNC:20059; USP33.
DR HPA; ENSG00000077254; Low tissue specificity.
DR MIM; 615146; gene.
DR neXtProt; NX_Q8TEY7; -.
DR OpenTargets; ENSG00000077254; -.
DR PharmGKB; PA134955343; -.
DR VEuPathDB; HostDB:ENSG00000077254; -.
DR eggNOG; KOG1870; Eukaryota.
DR GeneTree; ENSGT00940000157311; -.
DR HOGENOM; CLU_004896_0_0_1; -.
DR InParanoid; Q8TEY7; -.
DR OrthoDB; 147564at2759; -.
DR PhylomeDB; Q8TEY7; -.
DR TreeFam; TF352179; -.
DR PathwayCommons; Q8TEY7; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs.
DR SignaLink; Q8TEY7; -.
DR BioGRID-ORCS; 23032; 12 hits in 1128 CRISPR screens.
DR ChiTaRS; USP33; human.
DR EvolutionaryTrace; Q8TEY7; -.
DR GeneWiki; USP33; -.
DR GenomeRNAi; 23032; -.
DR Pharos; Q8TEY7; Tbio.
DR PRO; PR:Q8TEY7; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8TEY7; protein.
DR Bgee; ENSG00000077254; Expressed in cerebellar vermis and 210 other tissues.
DR ExpressionAtlas; Q8TEY7; baseline and differential.
DR Genevisible; Q8TEY7; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0030891; C:VCB complex; TAS:UniProtKB.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; IDA:UniProtKB.
DR GO; GO:0051298; P:centrosome duplication; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0032091; P:negative regulation of protein binding; IMP:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:CACAO.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:UniProtKB.
DR Gene3D; 3.30.2230.10; -; 2.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR035927; DUSP-like_sf.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR006615; Pept_C19_DUSP.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF06337; DUSP; 2.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR SMART; SM00695; DUSP; 2.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF143791; SSF143791; 2.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS51283; DUSP; 2.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Cytoskeleton; Endocytosis;
KW Golgi apparatus; Hydrolase; Metal-binding; Phosphoprotein; Protease;
KW Reference proteome; Repeat; Thiol protease; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..942
FT /note="Ubiquitin carboxyl-terminal hydrolase 33"
FT /id="PRO_0000080664"
FT DOMAIN 185..715
FT /note="USP"
FT DOMAIN 717..810
FT /note="DUSP 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT DOMAIN 818..921
FT /note="DUSP 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00613"
FT ZN_FING 37..140
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT REGION 294..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 419..469
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..354
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..440
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 194
FT /note="Nucleophile"
FT ACT_SITE 673
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 41
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 61
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 74
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 84
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 95
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 114
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 117
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1..31
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10470851,
FT ECO:0000303|PubMed:11739384"
FT /id="VSP_008591"
FT VAR_SEQ 552..559
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_008592"
FT VAR_SEQ 834..836
FT /note="LNR -> VKK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_008593"
FT VAR_SEQ 837..942
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_008594"
FT MUTAGEN 194
FT /note="C->S: Abolishes deubiquitinating activity. Does not
FT inhibit lysosomal trafficking of ADRB2; when associated
FT with Q-673."
FT /evidence="ECO:0000269|PubMed:19363159,
FT ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:23486064"
FT MUTAGEN 673
FT /note="H->Q: Abolishes deubiquitinating activity. Does not
FT inhibit lysosomal trafficking of ADRB2; when associated
FT with S-194."
FT /evidence="ECO:0000269|PubMed:19363159,
FT ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:23486064"
FT CONFLICT 241
FT /note="H -> Y (in Ref. 1; AAL78314/AAL78315 and 2;
FT BAA83049)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="S -> L (in Ref. 3; BAB14279)"
FT /evidence="ECO:0000305"
FT CONFLICT 617
FT /note="K -> R (in Ref. 3; BAB14279)"
FT /evidence="ECO:0000305"
FT HELIX 40..44
FT /evidence="ECO:0007829|PDB:2UZG"
FT HELIX 50..56
FT /evidence="ECO:0007829|PDB:2UZG"
FT TURN 57..59
FT /evidence="ECO:0007829|PDB:2UZG"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:2UZG"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:2UZG"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:2UZG"
FT HELIX 91..98
FT /evidence="ECO:0007829|PDB:2UZG"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:2UZG"
FT TURN 107..110
FT /evidence="ECO:0007829|PDB:2UZG"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:2UZG"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:2UZG"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:2UZG"
SQ SEQUENCE 942 AA; 106727 MW; 10A3AD632B901A74 CRC64;
MTGSNSHITI LTLKVLPHFE SLGKQEKIPN KMSAFRNHCP HLDSVGEITK EDLIQKSLGT
CQDCKVQGPN LWACLENRCS YVGCGESQVD HSTIHSQETK HYLTVNLTTL RVWCYACSKE
VFLDRKLGTQ PSLPHVRQPH QIQENSVQDF KIPSNTTLKT PLVAVFDDLD IEADEEDELR
ARGLTGLKNI GNTCYMNAAL QALSNCPPLT QFFLDCGGLA RTDKKPAICK SYLKLMTELW
HKSRPGSVVP TTLFQGIKTV NPTFRGYSQQ DAQEFLRCLM DLLHEELKEQ VMEVEEDPQT
ITTEETMEED KSQSDVDFQS CESCSNSDRA ENENGSRCFS EDNNETTMLI QDDENNSEMS
KDWQKEKMCN KINKVNSEGE FDKDRDSISE TVDLNNQETV KVQIHSRASE YITDVHSNDL
STPQILPSNE GVNPRLSASP PKSGNLWPGL APPHKKAQSA SPKRKKQHKK YRSVISDIFD
GTIISSVQCL TCDRVSVTLE TFQDLSLPIP GKEDLAKLHS SSHPTSIVKA GSCGEAYAPQ
GWIAFFMEYV KRFVVSCVPS WFWGPVVTLQ DCLAAFFARD ELKGDNMYSC EKCKKLRNGV
KFCKVQNFPE ILCIHLKRFR HELMFSTKIS THVSFPLEGL DLQPFLAKDS PAQIVTYDLL
SVICHHGTAS SGHYIAYCRN NLNNLWYEFD DQSVTEVSES TVQNAEAYVL FYRKSSEEAQ
KERRRISNLL NIMEPSLLQF YISRQWLNKF KTFAEPGPIS NNDFLCIHGG VPPRKAGYIE
DLVLMLPQNI WDNLYSRYGG GPAVNHLYIC HTCQIEAEKI EKRRKTELEI FIRLNRAFQK
EDSPATFYCI SMQWFREWES FVKGKDGDPP GPIDNTKIAV TKCGNVMLRQ GADSGQISEE
TWNFLQSIYG GGPEVILRPP VVHVDPDILQ AEEKIEVETR SL
