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 27-MAR-2024, entry version 188. 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/jci18348; 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 PubMed:23166351). Interacts with DIO2 (PubMed:12865408). Interacts with CC ROBO1. Interacts with SELENBP1; in a selenium-dependent manner CC (PubMed:19118533). Interacts with CCP110 (PubMed:23486064). CC {ECO:0000269|PubMed:11739384, ECO:0000269|PubMed:12865408, CC ECO:0000269|PubMed:19118533, ECO:0000269|PubMed:19363159, CC ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:23166351, CC ECO:0000269|PubMed:23486064}. CC -!- INTERACTION: CC Q8TEY7; P00533: EGFR; NbExp=2; IntAct=EBI-719283, EBI-297353; 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}; 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; 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; 140. DR CORUM; Q8TEY7; -. DR DIP; DIP-48942N; -. DR IntAct; Q8TEY7; 32. DR MINT; Q8TEY7; -. DR STRING; 9606.ENSP00000359829; -. DR MEROPS; C19.037; -. DR iPTMnet; Q8TEY7; -. DR PhosphoSitePlus; Q8TEY7; -. DR SwissPalm; Q8TEY7; -. DR BioMuta; USP33; -. DR DMDM; 116242838; -. DR EPD; Q8TEY7; -. DR jPOST; Q8TEY7; -. DR MassIVE; Q8TEY7; -. DR MaxQB; Q8TEY7; -. DR PaxDb; 9606-ENSP00000359829; -. DR PeptideAtlas; Q8TEY7; -. DR ProteomicsDB; 74526; -. [Q8TEY7-1] DR ProteomicsDB; 74527; -. [Q8TEY7-2] DR ProteomicsDB; 74528; -. [Q8TEY7-3] DR Pumba; Q8TEY7; -. DR Antibodypedia; 33489; 314 antibodies from 32 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 AGR; HGNC:20059; -. 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; 227085at2759; -. 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 SIGNOR; Q8TEY7; -. DR BioGRID-ORCS; 23032; 13 hits in 1209 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 212 other cell types or tissues. DR ExpressionAtlas; Q8TEY7; baseline and differential. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB. 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:HPA. 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 CDD; cd02674; Peptidase_C19R; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 2. DR Gene3D; 3.30.2230.10; DUSP-like; 2. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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 PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR21646:SF32; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 33; 1. 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; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF143791; DUSP-like; 2. DR SUPFAM; SSF57850; RING/U-box; 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. DR Genevisible; Q8TEY7; HS. 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 //