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Protein

Ubiquitin carboxyl-terminal hydrolase 33

Gene

USP33

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei194Nucleophile1
Active sitei673Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri59 – 123UBP-typePROSITE-ProRule annotationAdd BLAST65

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: UniProtKB
  • G protein-coupled receptor binding Source: UniProtKB
  • Ral GTPase binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processEndocytosis, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5689880 Ub-specific processing proteases
R-HSA-9010553 Regulation of expression of SLITs and ROBOs

Protein family/group databases

MEROPSiC19.037

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 33 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 33
Ubiquitin thioesterase 33
Ubiquitin-specific-processing protease 33
VHL-interacting deubiquitinating enzyme 1
Short name:
hVDU1
Gene namesi
Name:USP33
Synonyms:KIAA1097, VDU1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000077254.14
HGNCiHGNC:20059 USP33
MIMi615146 gene
neXtProtiNX_Q8TEY7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Golgi apparatus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi194C → S: Abolishes deubiquitinating activity. Does not inhibit lysosomal trafficking of ADRB2; when associated with Q-673. 3 Publications1
Mutagenesisi673H → Q: Abolishes deubiquitinating activity. Does not inhibit lysosomal trafficking of ADRB2; when associated with S-194. 3 Publications1

Organism-specific databases

DisGeNETi23032
OpenTargetsiENSG00000077254
PharmGKBiPA134955343

Polymorphism and mutation databases

BioMutaiUSP33
DMDMi116242838

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806641 – 942Ubiquitin carboxyl-terminal hydrolase 33Add BLAST942

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei377PhosphoserineCombined sources1
Modified residuei439PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated via a VHL-dependent pathway for proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8TEY7
MaxQBiQ8TEY7
PaxDbiQ8TEY7
PeptideAtlasiQ8TEY7
PRIDEiQ8TEY7
ProteomicsDBi74526
74527 [Q8TEY7-2]
74528 [Q8TEY7-3]

PTM databases

iPTMnetiQ8TEY7
PhosphoSitePlusiQ8TEY7

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Developmental stagei

Increased expression in S and early G2 phases and lower levels in late G2 and M phases.1 Publication

Gene expression databases

BgeeiENSG00000077254 Expressed in 237 organ(s), highest expression level in primary visual cortex
CleanExiHS_USP33
ExpressionAtlasiQ8TEY7 baseline and differential
GenevisibleiQ8TEY7 HS

Organism-specific databases

HPAiHPA005719

Interactioni

Subunit structurei

Interacts with VHL, leading to its ubiquitination and subsequent degradation. Interacts with ARRB1, ARRB2, ADRB2, DIO2 and ROBO1. Interacts with SELENBP1; in a selenium-dependent manner. Interacts with CCP110.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SELENBP1Q132285EBI-719307,EBI-711619

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116671, 57 interactors
CORUMiQ8TEY7
DIPiDIP-48942N
IntActiQ8TEY7, 10 interactors
MINTiQ8TEY7
STRINGi9606.ENSP00000350009

Structurei

Secondary structure

1942
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8TEY7
SMRiQ8TEY7
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8TEY7

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini185 – 715USPAdd BLAST531
Domaini717 – 810DUSP 1PROSITE-ProRule annotationAdd BLAST94
Domaini818 – 921DUSP 2PROSITE-ProRule annotationAdd BLAST104

Domaini

The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 86 is replaced by a Glu residue.1 Publication

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri59 – 123UBP-typePROSITE-ProRule annotationAdd BLAST65

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IN4T Eukaryota
ENOG410ZG0F LUCA
GeneTreeiENSGT00860000133682
HOGENOMiHOG000286031
HOVERGENiHBG054196
InParanoidiQ8TEY7
KOiK11848
OMAiCMASFFS
OrthoDBiEOG091G02UV
PhylomeDBiQ8TEY7
TreeFamiTF352179

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR035927 DUSP-like_sf
IPR038765 Papain_like_cys_pep_sf
IPR006615 Pept_C19_DUSP
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
IPR013083 Znf_RING/FYVE/PHD
IPR001607 Znf_UBP
PfamiView protein in Pfam
PF06337 DUSP, 2 hits
PF00443 UCH, 1 hit
PF02148 zf-UBP, 1 hit
SMARTiView protein in SMART
SM00695 DUSP, 2 hits
SM00290 ZnF_UBP, 1 hit
SUPFAMiSSF143791 SSF143791, 2 hits
SSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS51283 DUSP, 2 hits
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
PS50271 ZF_UBP, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8TEY7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MTGSNSHITI LTLKVLPHFE SLGKQEKIPN KMSAFRNHCP HLDSVGEITK
60 70 80 90 100
EDLIQKSLGT CQDCKVQGPN LWACLENRCS YVGCGESQVD HSTIHSQETK
110 120 130 140 150
HYLTVNLTTL RVWCYACSKE VFLDRKLGTQ PSLPHVRQPH QIQENSVQDF
160 170 180 190 200
KIPSNTTLKT PLVAVFDDLD IEADEEDELR ARGLTGLKNI GNTCYMNAAL
210 220 230 240 250
QALSNCPPLT QFFLDCGGLA RTDKKPAICK SYLKLMTELW HKSRPGSVVP
260 270 280 290 300
TTLFQGIKTV NPTFRGYSQQ DAQEFLRCLM DLLHEELKEQ VMEVEEDPQT
310 320 330 340 350
ITTEETMEED KSQSDVDFQS CESCSNSDRA ENENGSRCFS EDNNETTMLI
360 370 380 390 400
QDDENNSEMS KDWQKEKMCN KINKVNSEGE FDKDRDSISE TVDLNNQETV
410 420 430 440 450
KVQIHSRASE YITDVHSNDL STPQILPSNE GVNPRLSASP PKSGNLWPGL
460 470 480 490 500
APPHKKAQSA SPKRKKQHKK YRSVISDIFD GTIISSVQCL TCDRVSVTLE
510 520 530 540 550
TFQDLSLPIP GKEDLAKLHS SSHPTSIVKA GSCGEAYAPQ GWIAFFMEYV
560 570 580 590 600
KRFVVSCVPS WFWGPVVTLQ DCLAAFFARD ELKGDNMYSC EKCKKLRNGV
610 620 630 640 650
KFCKVQNFPE ILCIHLKRFR HELMFSTKIS THVSFPLEGL DLQPFLAKDS
660 670 680 690 700
PAQIVTYDLL SVICHHGTAS SGHYIAYCRN NLNNLWYEFD DQSVTEVSES
710 720 730 740 750
TVQNAEAYVL FYRKSSEEAQ KERRRISNLL NIMEPSLLQF YISRQWLNKF
760 770 780 790 800
KTFAEPGPIS NNDFLCIHGG VPPRKAGYIE DLVLMLPQNI WDNLYSRYGG
810 820 830 840 850
GPAVNHLYIC HTCQIEAEKI EKRRKTELEI FIRLNRAFQK EDSPATFYCI
860 870 880 890 900
SMQWFREWES FVKGKDGDPP GPIDNTKIAV TKCGNVMLRQ GADSGQISEE
910 920 930 940
TWNFLQSIYG GGPEVILRPP VVHVDPDILQ AEEKIEVETR SL
Length:942
Mass (Da):106,727
Last modified:October 17, 2006 - v2
Checksum:i10A3AD632B901A74
GO
Isoform 2 (identifier: Q8TEY7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-31: Missing.

Show »
Length:911
Mass (Da):103,283
Checksum:i7F3F40A75F764624
GO
Isoform 3 (identifier: Q8TEY7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     552-559: Missing.
     834-836: LNR → VKK
     837-942: Missing.

Show »
Length:828
Mass (Da):93,957
Checksum:iA6A5D23B288BFC00
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PQP0E9PQP0_HUMAN
Ubiquitinyl hydrolase 1
USP33
202Annotation score:
H0YCV3H0YCV3_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP33
456Annotation score:
H0YD08H0YD08_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP33
139Annotation score:
E9PP47E9PP47_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP33
72Annotation score:
E9PLK7E9PLK7_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP33
110Annotation score:

Sequence cautioni

The sequence BAA83049 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti241H → Y in AAL78314 (PubMed:11739384).Curated1
Sequence conflicti241H → Y in AAL78315 (PubMed:11739384).Curated1
Sequence conflicti241H → Y in BAA83049 (PubMed:10470851).Curated1
Sequence conflicti428S → L in BAB14279 (PubMed:14702039).Curated1
Sequence conflicti617K → R in BAB14279 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0085911 – 31Missing in isoform 2. 2 PublicationsAdd BLAST31
Alternative sequenceiVSP_008592552 – 559Missing in isoform 3. 2 Publications8
Alternative sequenceiVSP_008593834 – 836LNR → VKK in isoform 3. 2 Publications3
Alternative sequenceiVSP_008594837 – 942Missing in isoform 3. 2 PublicationsAdd BLAST106

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF383172 mRNA Translation: AAL78314.1
AF383173 mRNA Translation: AAL78315.1
AB029020 mRNA Translation: BAA83049.1 Different initiation.
AK022864 mRNA Translation: BAB14279.1
AC114487 Genomic DNA No translation available.
BC016663 mRNA Translation: AAH16663.1
CCDSiCCDS678.1 [Q8TEY7-1]
CCDS679.1 [Q8TEY7-2]
CCDS680.1 [Q8TEY7-3]
RefSeqiNP_055832.3, NM_015017.4 [Q8TEY7-1]
NP_963918.1, NM_201624.2 [Q8TEY7-2]
NP_963920.1, NM_201626.2 [Q8TEY7-3]
UniGeneiHs.480597

Genome annotation databases

EnsembliENST00000357428; ENSP00000350009; ENSG00000077254 [Q8TEY7-1]
ENST00000370792; ENSP00000359828; ENSG00000077254 [Q8TEY7-3]
ENST00000370793; ENSP00000359829; ENSG00000077254 [Q8TEY7-1]
ENST00000370794; ENSP00000359830; ENSG00000077254 [Q8TEY7-2]
GeneIDi23032
KEGGihsa:23032
UCSCiuc001dht.5 human [Q8TEY7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF383172 mRNA Translation: AAL78314.1
AF383173 mRNA Translation: AAL78315.1
AB029020 mRNA Translation: BAA83049.1 Different initiation.
AK022864 mRNA Translation: BAB14279.1
AC114487 Genomic DNA No translation available.
BC016663 mRNA Translation: AAH16663.1
CCDSiCCDS678.1 [Q8TEY7-1]
CCDS679.1 [Q8TEY7-2]
CCDS680.1 [Q8TEY7-3]
RefSeqiNP_055832.3, NM_015017.4 [Q8TEY7-1]
NP_963918.1, NM_201624.2 [Q8TEY7-2]
NP_963920.1, NM_201626.2 [Q8TEY7-3]
UniGeneiHs.480597

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2UZGNMR-A36-130[»]
ProteinModelPortaliQ8TEY7
SMRiQ8TEY7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116671, 57 interactors
CORUMiQ8TEY7
DIPiDIP-48942N
IntActiQ8TEY7, 10 interactors
MINTiQ8TEY7
STRINGi9606.ENSP00000350009

Protein family/group databases

MEROPSiC19.037

PTM databases

iPTMnetiQ8TEY7
PhosphoSitePlusiQ8TEY7

Polymorphism and mutation databases

BioMutaiUSP33
DMDMi116242838

Proteomic databases

EPDiQ8TEY7
MaxQBiQ8TEY7
PaxDbiQ8TEY7
PeptideAtlasiQ8TEY7
PRIDEiQ8TEY7
ProteomicsDBi74526
74527 [Q8TEY7-2]
74528 [Q8TEY7-3]

Protocols and materials databases

DNASUi23032
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357428; ENSP00000350009; ENSG00000077254 [Q8TEY7-1]
ENST00000370792; ENSP00000359828; ENSG00000077254 [Q8TEY7-3]
ENST00000370793; ENSP00000359829; ENSG00000077254 [Q8TEY7-1]
ENST00000370794; ENSP00000359830; ENSG00000077254 [Q8TEY7-2]
GeneIDi23032
KEGGihsa:23032
UCSCiuc001dht.5 human [Q8TEY7-1]

Organism-specific databases

CTDi23032
DisGeNETi23032
EuPathDBiHostDB:ENSG00000077254.14
GeneCardsiUSP33
H-InvDBiHIX0159957
HGNCiHGNC:20059 USP33
HPAiHPA005719
MIMi615146 gene
neXtProtiNX_Q8TEY7
OpenTargetsiENSG00000077254
PharmGKBiPA134955343
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IN4T Eukaryota
ENOG410ZG0F LUCA
GeneTreeiENSGT00860000133682
HOGENOMiHOG000286031
HOVERGENiHBG054196
InParanoidiQ8TEY7
KOiK11848
OMAiCMASFFS
OrthoDBiEOG091G02UV
PhylomeDBiQ8TEY7
TreeFamiTF352179

Enzyme and pathway databases

ReactomeiR-HSA-5689880 Ub-specific processing proteases
R-HSA-9010553 Regulation of expression of SLITs and ROBOs

Miscellaneous databases

ChiTaRSiUSP33 human
EvolutionaryTraceiQ8TEY7
GeneWikiiUSP33
GenomeRNAii23032
PROiPR:Q8TEY7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000077254 Expressed in 237 organ(s), highest expression level in primary visual cortex
CleanExiHS_USP33
ExpressionAtlasiQ8TEY7 baseline and differential
GenevisibleiQ8TEY7 HS

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR035927 DUSP-like_sf
IPR038765 Papain_like_cys_pep_sf
IPR006615 Pept_C19_DUSP
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
IPR013083 Znf_RING/FYVE/PHD
IPR001607 Znf_UBP
PfamiView protein in Pfam
PF06337 DUSP, 2 hits
PF00443 UCH, 1 hit
PF02148 zf-UBP, 1 hit
SMARTiView protein in SMART
SM00695 DUSP, 2 hits
SM00290 ZnF_UBP, 1 hit
SUPFAMiSSF143791 SSF143791, 2 hits
SSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS51283 DUSP, 2 hits
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
PS50271 ZF_UBP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBP33_HUMAN
AccessioniPrimary (citable) accession number: Q8TEY7
Secondary accession number(s): Q8TEY6
, Q96AV6, Q9H9F0, Q9UPQ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: October 17, 2006
Last modified: November 7, 2018
This is version 157 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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