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Protein

Ubiquitin carboxyl-terminal hydrolase 33

Gene

Usp33

Organism
Mus musculus (Mouse)
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.2 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 sitei163NucleophilePROSITE-ProRule annotation1
Active sitei640Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri28 – 92UBP-typePROSITE-ProRule annotationAdd BLAST65

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-5689880 Ub-specific processing proteases
R-MMU-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
Gene namesi
Name:Usp33
Synonyms:Vdu1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:2159711 Usp33

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003904241 – 909Ubiquitin carboxyl-terminal hydrolase 33Add BLAST909

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei407PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated via a VHL-dependent pathway for proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ8R5K2
PRIDEiQ8R5K2

PTM databases

iPTMnetiQ8R5K2
PhosphoSitePlusiQ8R5K2

Expressioni

Tissue specificityi

Present in E9.5 and E11.5 commissural neurons (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000025437
ExpressionAtlasiQ8R5K2 baseline and differential
GenevisibleiQ8R5K2 MM

Interactioni

Subunit structurei

Interacts with VHL, leading to its ubiquitination and subsequent degradation. Interacts with ARRB1, ARRB2, ADRB2 and DIO2. Interacts with SELENBP1; in a selenium-dependent manner. Interacts with CCP110 (By similarity). Interacts with ROBO1.By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi228458, 2 interactors
IntActiQ8R5K2, 1 interactor
STRINGi10090.ENSMUSP00000113265

Structurei

3D structure databases

ProteinModelPortaliQ8R5K2
SMRiQ8R5K2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini154 – 682USPAdd BLAST529
Domaini684 – 777DUSP 1PROSITE-ProRule annotationAdd BLAST94
Domaini785 – 888DUSP 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 55 is replaced by a Glu residue (By similarity).By similarity

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri28 – 92UBP-typePROSITE-ProRule annotationAdd BLAST65

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1870 Eukaryota
COG5560 LUCA
GeneTreeiENSGT00860000133682
HOGENOMiHOG000286031
HOVERGENiHBG054196
InParanoidiQ8R5K2
KOiK11848
OMAiPRKAGYI
OrthoDBiEOG091G02UV
PhylomeDBiQ8R5K2
TreeFamiTF352179

Family and domain databases

Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR035927 DUSP-like_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
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8R5K2-1) [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
MTTFRNHCPH LDSVGEITKE DLIQKSLGAC QDCKVRGPNL WACLENRCSY
60 70 80 90 100
VGCGESQVDH STIHSQETKH YLTVNLTTLR VWCYACSKEV FLDRKLGTPP
110 120 130 140 150
SLPHVRQPQQ TQENSVQDFK IPSNPALKTP MVAVSEDLDI EVEEEDELKA
160 170 180 190 200
RGLTGLKNIG NTCYMNAALQ ALSNCPPLTQ FFLDCGGLAR TDKKPAICKS
210 220 230 240 250
YLKLMTELWH KSRPGSVVPA NLFQGIKTVN PTFRGYSQQD AQEFLRCLMD
260 270 280 290 300
LLHEELKEQV MEMEEEPQTL TSEETVEEEK SQSDVDFQSC ESCSSSEKAE
310 320 330 340 350
NESGSKGFPE DSNETTMLIQ DEDDLEMAKD WQKEKVCNKI NKANADVELD
360 370 380 390 400
KDRDTVCETV DLNSQETVKV QIHGRASESI TDVHLNDLAT SQILPSNESV
410 420 430 440 450
SPRLSASPPK LGSLWPGLSP PHKKAQSTSA KRKKQHKKYR SVISDIFDGT
460 470 480 490 500
VISSVQCLTC DRVSITLETF QDLSLPIPGK EDLAKLHSSS HPTIVKAGSC
510 520 530 540 550
GEAYAPQGWI AFFMEYVKRF VVSCVPSWFW GPVVTLQDCL AAFFARDELK
560 570 580 590 600
GDNMYSCEKC KKLRNGVKFC KVQKFPEILC IHLKRFRHEL MFSTKISTHV
610 620 630 640 650
SFPLEGLDLQ PFLAKDSPAQ IVTYDLLSVI CHHGTASSGH YIAYCRNNLN
660 670 680 690 700
NLWYEFDDQS VTEVSESTVQ NAEAYVLFYR KSSEEAQKER RRISNLLNIM
710 720 730 740 750
EPSLLQFYIS RQWLNKFKTF AEPGPISNND FLCIHGGIPP RKASYIEDLV
760 770 780 790 800
LMLPQNIWDN LYSRYGGGPA VNHLYICHTC QIELEKIEKR RKTELEIFIR
810 820 830 840 850
LNRAFQEEDS PATFYCISMQ WFREWESFVK GKDGDPPGPI DNTKIAVTKC
860 870 880 890 900
GSVMLKQGAD SGQISEETWN FLQSIYGGGP EVILRPPVVH VDPDVLQAEE

KIEVETRSL
Length:909
Mass (Da):102,728
Last modified:December 15, 2009 - v2
Checksum:iF8A2BDA9FBCD633A
GO
Isoform 2 (identifier: Q8R5K2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     519-526: Missing.

Note: No experimental confirmation available.
Show »
Length:901
Mass (Da):101,839
Checksum:i6154729A27ED06BE
GO

Sequence cautioni

The sequence AAH05506 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH89315 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti309P → S in AAL78316 (PubMed:11739384).Curated1
Sequence conflicti411L → P in AAL78316 (PubMed:11739384).Curated1
Sequence conflicti411L → P in AAH05506 (PubMed:15489334).Curated1
Sequence conflicti465I → V in AAL78316 (PubMed:11739384).Curated1
Sequence conflicti465I → V in AAH05506 (PubMed:15489334).Curated1
Sequence conflicti779T → S in AAH89315 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038531519 – 526Missing in isoform 2. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF383174 mRNA Translation: AAL78316.1
BC005506 mRNA Translation: AAH05506.1 Different initiation.
BC031366 mRNA Translation: AAH31366.1
BC089315 mRNA Translation: AAH89315.1 Different initiation.
AK143844 mRNA Translation: BAE25565.1
CCDSiCCDS17918.1 [Q8R5K2-1]
CCDS57261.1 [Q8R5K2-2]
RefSeqiNP_001239415.1, NM_001252486.1 [Q8R5K2-2]
NP_573510.2, NM_133247.3 [Q8R5K2-1]
UniGeneiMm.258320

Genome annotation databases

EnsembliENSMUST00000117492; ENSMUSP00000113265; ENSMUSG00000025437 [Q8R5K2-2]
ENSMUST00000197748; ENSMUSP00000142708; ENSMUSG00000025437 [Q8R5K2-1]
GeneIDi170822
KEGGimmu:170822
UCSCiuc008rti.2 mouse [Q8R5K2-1]
uc008rtj.2 mouse [Q8R5K2-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiUBP33_MOUSE
AccessioniPrimary (citable) accession number: Q8R5K2
Secondary accession number(s): Q3UP32
, Q5FWK0, Q8K0I3, Q99K22
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 2009
Last sequence update: December 15, 2009
Last modified: April 25, 2018
This is version 120 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health