CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-018086
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ubiquitin carboxyl-terminal hydrolase 33 
Protein Synonyms/Alias
 Deubiquitinating enzyme 33; Ubiquitin thioesterase 33; Ubiquitin-specific-processing protease 33; VHL-interacting deubiquitinating enzyme 1; hVDU1 
Gene Name
 USP33 
Gene Synonyms/Alias
 KIAA1097; VDU1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
50DSVGEITKEDLIQKSubiquitination[1]
65LGTCQDCKVQGPNLWubiquitination[1]
126KEVFLDRKLGTQPSLubiquitination[2]
258TTLFQGIKTVNPTFRubiquitination[1, 3, 4, 5]
361ENNSEMSKDWQKEKMubiquitination[3]
365EMSKDWQKEKMCNKIubiquitination[1, 3]
367SKDWQKEKMCNKINKubiquitination[1]
383NSEGEFDKDRDSISEubiquitination[2, 5]
512LSLPIPGKEDLAKLHubiquitination[2]
617EILCIHLKRFRHELMubiquitination[1]
863REWESFVKGKDGDPPubiquitination[2, 5]
865WESFVKGKDGDPPGPubiquitination[2]
882NTKIAVTKCGNVMLRubiquitination[1, 3, 6]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 
Functional Description
 Deubiquitinating enzyme involved in various processes such as centrosome duplication, cellular migration and beta-2 adrenergic receptor/ADRB2 recycling. Involved in regulation of centrosome duplication by mediating deubiquitination of CCP110 in S and G2/M phase, leading to stabilize CCP110 during the period which centrioles duplicate and elongate. Involved in cell migration via its interaction with intracellular domain of ROBO1, leading to regulate the Slit signaling. Plays a role in commissural axon guidance cross the ventral midline of the neural tube in a Slit-dependent manner, possibly by mediating the deubiquitination of ROBO1. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination of beta-arrestins (ARRB1 and ARRB2) and beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta- arrestins, leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. 
Sequence Annotation
 DOMAIN 717 810 DUSP 1.
 DOMAIN 818 921 DUSP 2.
 ZN_FING 59 123 UBP-type.
 ACT_SITE 194 194 Nucleophile.
 ACT_SITE 673 673 Proton acceptor (By similarity).
 MOD_RES 439 439 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Cytoskeleton; Endocytosis; Golgi apparatus; Hydrolase; Metal-binding; Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 942 AA 
Protein Sequence
MTGSNSHITI LTLKVLPHFE SLGKQEKIPN KMSAFRNHCP HLDSVGEITK EDLIQKSLGT 60
CQDCKVQGPN LWACLENRCS YVGCGESQVD HSTIHSQETK HYLTVNLTTL RVWCYACSKE 120
VFLDRKLGTQ PSLPHVRQPH QIQENSVQDF KIPSNTTLKT PLVAVFDDLD IEADEEDELR 180
ARGLTGLKNI GNTCYMNAAL QALSNCPPLT QFFLDCGGLA RTDKKPAICK SYLKLMTELW 240
HKSRPGSVVP TTLFQGIKTV NPTFRGYSQQ DAQEFLRCLM DLLHEELKEQ VMEVEEDPQT 300
ITTEETMEED KSQSDVDFQS CESCSNSDRA ENENGSRCFS EDNNETTMLI QDDENNSEMS 360
KDWQKEKMCN KINKVNSEGE FDKDRDSISE TVDLNNQETV KVQIHSRASE YITDVHSNDL 420
STPQILPSNE GVNPRLSASP PKSGNLWPGL APPHKKAQSA SPKRKKQHKK YRSVISDIFD 480
GTIISSVQCL TCDRVSVTLE TFQDLSLPIP GKEDLAKLHS SSHPTSIVKA GSCGEAYAPQ 540
GWIAFFMEYV KRFVVSCVPS WFWGPVVTLQ DCLAAFFARD ELKGDNMYSC EKCKKLRNGV 600
KFCKVQNFPE ILCIHLKRFR HELMFSTKIS THVSFPLEGL DLQPFLAKDS PAQIVTYDLL 660
SVICHHGTAS SGHYIAYCRN NLNNLWYEFD DQSVTEVSES TVQNAEAYVL FYRKSSEEAQ 720
KERRRISNLL NIMEPSLLQF YISRQWLNKF KTFAEPGPIS NNDFLCIHGG VPPRKAGYIE 780
DLVLMLPQNI WDNLYSRYGG GPAVNHLYIC HTCQIEAEKI EKRRKTELEI FIRLNRAFQK 840
EDSPATFYCI SMQWFREWES FVKGKDGDPP GPIDNTKIAV TKCGNVMLRQ GADSGQISEE 900
TWNFLQSIYG GGPEVILRPP VVHVDPDILQ AEEKIEVETR SL 942 
Gene Ontology
 GO:0044297; C:cell body; IEA:Compara.
 GO:0005813; C:centrosome; IDA:UniProtKB.
 GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
 GO:0030891; C:VCB complex; TAS:UniProtKB.
 GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
 GO:0004221; F:ubiquitin thiolesterase activity; IDA:UniProtKB.
 GO:0004843; F:ubiquitin-specific protease activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0007411; P:axon guidance; ISS:UniProtKB.
 GO:0016477; P:cell migration; ISS:UniProtKB.
 GO:0051298; P:centrosome duplication; IMP:UniProtKB.
 GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
 GO:0071108; P:protein K48-linked deubiquitination; IDA:UniProtKB.
 GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
 GO:0008277; P:regulation of G-protein coupled receptor protein signaling pathway; IMP:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:UniProtKB. 
Interpro
 IPR006615; Pept_C19_DUSP.
 IPR018200; Pept_C19ubi-hydrolase_C_CS.
 IPR001394; Peptidase_C19.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR001607; Znf_UBP. 
Pfam
 PF06337; DUSP
 PF00443; UCH
 PF02148; zf-UBP 
SMART
 SM00695; DUSP 
PROSITE
 PS51283; DUSP
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3
 PS50271; ZF_UBP 
PRINTS