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Protein

Ubiquitin carboxyl-terminal hydrolase 33

Gene

USP33

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • axon guidance Source: UniProtKB
  • cell migration Source: UniProtKB
  • cellular response to starvation Source: UniProtKB
  • centrosome duplication Source: UniProtKB
  • endocytosis Source: UniProtKB-KW
  • negative regulation of protein binding Source: UniProtKB
  • positive regulation of protein binding Source: UniProtKB
  • protein deubiquitination Source: UniProtKB
  • protein K48-linked deubiquitination Source: UniProtKB
  • protein K63-linked deubiquitination Source: UniProtKB
  • protein stabilization Source: CACAO
  • regulation of autophagy Source: UniProtKB
  • regulation of G-protein coupled receptor protein signaling pathway Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Endocytosis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS01237-MONOMER.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.

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

HGNCiHGNC:20059. USP33.

Subcellular locationi

Isoform 3 :

GO - Cellular componenti

  • cell body Source: Ensembl
  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • focal adhesion Source: HPA
  • Golgi apparatus Source: UniProtKB
  • nucleoplasm Source: HPA
  • perinuclear region of cytoplasm Source: UniProtKB
  • VCB complex Source: UniProtKB
Complete GO annotation...

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.

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.
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

  • G-protein coupled receptor binding Source: UniProtKB
  • Ral GTPase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116671. 46 interactors.
DIPiDIP-48942N.
IntActiQ8TEY7. 8 interactors.
MINTiMINT-1370210.
STRINGi9606.ENSP00000350009.

Structurei

Secondary structure

1942
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi40 – 44Combined sources5
Helixi50 – 56Combined sources7
Turni57 – 59Combined sources3
Beta strandi62 – 64Combined sources3
Beta strandi72 – 74Combined sources3
Turni86 – 89Combined sources4
Helixi91 – 98Combined sources8
Beta strandi103 – 106Combined sources4
Turni107 – 110Combined sources4
Beta strandi111 – 114Combined sources4
Turni115 – 118Combined sources4
Beta strandi119 – 121Combined sources3

3D structure databases

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

Contains 2 DUSP domains.PROSITE-ProRule annotation
Contains 1 UBP-type zinc finger.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

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.
OMAiICNKINK.
OrthoDBiEOG091G02UV.
PhylomeDBiQ8TEY7.
TreeFamiTF352179.

Family and domain databases

Gene3Di3.30.2230.10. 2 hits.
3.30.40.10. 1 hit.
InterProiIPR006615. Pept_C19_DUSP.
IPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PfamiPF06337. DUSP. 2 hits.
PF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
SMARTiSM00695. DUSP. 2 hits.
SM00290. ZnF_UBP. 1 hit.
[Graphical view]
SUPFAMiSSF143791. SSF143791. 2 hits.
PROSITEiPS51283. DUSP. 2 hits.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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

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

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. 46 interactors.
DIPiDIP-48942N.
IntActiQ8TEY7. 8 interactors.
MINTiMINT-1370210.
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.

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.
GeneCardsiUSP33.
H-InvDBHIX0159957.
HGNCiHGNC:20059. USP33.
HPAiHPA005719.
MIMi615146. gene.
neXtProtiNX_Q8TEY7.
OpenTargetsiENSG00000077254.
PharmGKBiPA134955343.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS01237-MONOMER.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.

Miscellaneous databases

ChiTaRSiUSP33. human.
EvolutionaryTraceiQ8TEY7.
GeneWikiiUSP33.
GenomeRNAii23032.
PROiQ8TEY7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000077254.
CleanExiHS_USP33.
ExpressionAtlasiQ8TEY7. baseline and differential.
GenevisibleiQ8TEY7. HS.

Family and domain databases

Gene3Di3.30.2230.10. 2 hits.
3.30.40.10. 1 hit.
InterProiIPR006615. Pept_C19_DUSP.
IPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PfamiPF06337. DUSP. 2 hits.
PF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
SMARTiSM00695. DUSP. 2 hits.
SM00290. ZnF_UBP. 1 hit.
[Graphical view]
SUPFAMiSSF143791. SSF143791. 2 hits.
PROSITEiPS51283. DUSP. 2 hits.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP33_HUMAN
AccessioniPrimary (citable) accession number: Q8TEY7
Secondary accession number(s): Q8TEY6
, Q96AV6, Q9H9F0, Q9UPQ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 145 of the entry and version 2 of the sequence. [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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.