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Q8R5K2 (UBP33_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Usp33
Synonyms:Vdu1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length909 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.5

Catalytic activity

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).

Subunit structure

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. Ref.4 Ref.5

Subcellular location

Cytoplasmperinuclear region By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Note: Associates with centrosomes predominantly in S and G2 phases but less in G1 phase By similarity.

Tissue specificity

Present in E9.5 and E11.5 commissural neurons (at protein level). Ref.4

Domain

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.

Post-translational modification

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

Sequence similarities

Belongs to the peptidase C19 family. USP20/USP33 subfamily.

Contains 2 DUSP domains.

Contains 1 UBP-type zinc finger.

Contains 1 USP domain.

Sequence caution

The sequence AAH05506.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH89315.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processEndocytosis
Ubl conjugation pathway
   Cellular componentCytoplasm
Cytoskeleton
   Coding sequence diversityAlternative splicing
   DomainRepeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Protease
Thiol protease
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaxon guidance

Inferred from mutant phenotype Ref.5. Source: UniProtKB

cell migration

Inferred from mutant phenotype Ref.5. Source: UniProtKB

centrosome duplication

Inferred from sequence or structural similarity. Source: UniProtKB

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

protein K48-linked deubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein K63-linked deubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

protein deubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of G-protein coupled receptor protein signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcell body

Inferred from direct assay Ref.4. Source: MGI

centrosome

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncysteine-type endopeptidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.5. Source: UniProtKB

ubiquitin thiolesterase activity

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8R5K2-1)

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.
Isoform 2 (identifier: Q8R5K2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     519-526: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 909909Ubiquitin carboxyl-terminal hydrolase 33
PRO_0000390424

Regions

Domain154 – 682529USP
Domain684 – 77794DUSP 1
Domain785 – 888104DUSP 2
Zinc finger28 – 9265UBP-type

Sites

Active site1631Nucleophile By similarity
Active site6401Proton acceptor By similarity

Amino acid modifications

Modified residue4071Phosphoserine By similarity

Natural variations

Alternative sequence519 – 5268Missing in isoform 2.
VSP_038531

Experimental info

Sequence conflict3091P → S in AAL78316. Ref.1
Sequence conflict4111L → P in AAL78316. Ref.1
Sequence conflict4111L → P in AAH05506. Ref.2
Sequence conflict4651I → V in AAL78316. Ref.1
Sequence conflict4651I → V in AAH05506. Ref.2
Sequence conflict7791T → S in AAH89315. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 15, 2009. Version 2.
Checksum: F8A2BDA9FBCD633A

FASTA909102,728
        10         20         30         40         50         60 
MTTFRNHCPH LDSVGEITKE DLIQKSLGAC QDCKVRGPNL WACLENRCSY VGCGESQVDH 

        70         80         90        100        110        120 
STIHSQETKH YLTVNLTTLR VWCYACSKEV FLDRKLGTPP SLPHVRQPQQ TQENSVQDFK 

       130        140        150        160        170        180 
IPSNPALKTP MVAVSEDLDI EVEEEDELKA RGLTGLKNIG NTCYMNAALQ ALSNCPPLTQ 

       190        200        210        220        230        240 
FFLDCGGLAR TDKKPAICKS YLKLMTELWH KSRPGSVVPA NLFQGIKTVN PTFRGYSQQD 

       250        260        270        280        290        300 
AQEFLRCLMD LLHEELKEQV MEMEEEPQTL TSEETVEEEK SQSDVDFQSC ESCSSSEKAE 

       310        320        330        340        350        360 
NESGSKGFPE DSNETTMLIQ DEDDLEMAKD WQKEKVCNKI NKANADVELD KDRDTVCETV 

       370        380        390        400        410        420 
DLNSQETVKV QIHGRASESI TDVHLNDLAT SQILPSNESV SPRLSASPPK LGSLWPGLSP 

       430        440        450        460        470        480 
PHKKAQSTSA KRKKQHKKYR SVISDIFDGT VISSVQCLTC DRVSITLETF QDLSLPIPGK 

       490        500        510        520        530        540 
EDLAKLHSSS HPTIVKAGSC GEAYAPQGWI AFFMEYVKRF VVSCVPSWFW GPVVTLQDCL 

       550        560        570        580        590        600 
AAFFARDELK GDNMYSCEKC KKLRNGVKFC KVQKFPEILC IHLKRFRHEL MFSTKISTHV 

       610        620        630        640        650        660 
SFPLEGLDLQ PFLAKDSPAQ IVTYDLLSVI CHHGTASSGH YIAYCRNNLN NLWYEFDDQS 

       670        680        690        700        710        720 
VTEVSESTVQ NAEAYVLFYR KSSEEAQKER RRISNLLNIM EPSLLQFYIS RQWLNKFKTF 

       730        740        750        760        770        780 
AEPGPISNND FLCIHGGIPP RKASYIEDLV LMLPQNIWDN LYSRYGGGPA VNHLYICHTC 

       790        800        810        820        830        840 
QIELEKIEKR RKTELEIFIR LNRAFQEEDS PATFYCISMQ WFREWESFVK GKDGDPPGPI 

       850        860        870        880        890        900 
DNTKIAVTKC GSVMLKQGAD SGQISEETWN FLQSIYGGGP EVILRPPVVH VDPDVLQAEE 


KIEVETRSL 

« Hide

Isoform 2 [UniParc].

Checksum: 6154729A27ED06BE
Show »

FASTA901101,839

References

« Hide 'large scale' references
[1]"Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel-Lindau tumor suppressor protein."
Li Z., Na X., Wang D., Schoen S.R., Messing E.M., Wu G.
J. Biol. Chem. 277:4656-4662(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 225-909 (ISOFORM 1).
Strain: C57BL/6 and FVB/N.
Tissue: Brain, Eye and Mammary tumor.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-880 (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Spleen.
[4]"Midline crossing and Slit responsiveness of commissural axons require USP33."
Yuasa-Kawada J., Kinoshita-Kawada M., Wu G., Rao Y., Wu J.Y.
Nat. Neurosci. 12:1087-1089(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ROBO1, TISSUE SPECIFICITY.
[5]"Deubiquitinating enzyme USP33/VDU1 is required for Slit signaling in inhibiting breast cancer cell migration."
Yuasa-Kawada J., Kinoshita-Kawada M., Rao Y., Wu J.Y.
Proc. Natl. Acad. Sci. U.S.A. 106:14530-14535(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ROBO1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS17918.1. [Q8R5K2-1]
CCDS57261.1. [Q8R5K2-2]
RefSeqNP_001239415.1. NM_001252486.1. [Q8R5K2-2]
NP_573510.2. NM_133247.3. [Q8R5K2-1]
UniGeneMm.258320.

3D structure databases

ProteinModelPortalQ8R5K2.
SMRQ8R5K2. Positions 5-392, 413-683.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid228458. 1 interaction.

Protein family/group databases

MEROPSC19.037.

PTM databases

PhosphoSiteQ8R5K2.

Proteomic databases

PaxDbQ8R5K2.
PRIDEQ8R5K2.

Protocols and materials databases

DNASU170822.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026507; ENSMUSP00000026507; ENSMUSG00000025437. [Q8R5K2-2]
ENSMUST00000117492; ENSMUSP00000113265; ENSMUSG00000025437. [Q8R5K2-1]
GeneID170822.
KEGGmmu:170822.
UCSCuc008rti.2. mouse. [Q8R5K2-1]
uc008rtj.2. mouse. [Q8R5K2-2]

Organism-specific databases

CTD23032.
MGIMGI:2159711. Usp33.

Phylogenomic databases

eggNOGCOG5560.
GeneTreeENSGT00750000117701.
HOGENOMHOG000286031.
HOVERGENHBG054196.
InParanoidQ8R5K2.
KOK11848.
OMALPSNEGV.
OrthoDBEOG7CRTP2.
PhylomeDBQ8R5K2.
TreeFamTF352179.

Gene expression databases

ArrayExpressQ8R5K2.
BgeeQ8R5K2.
GenevestigatorQ8R5K2.

Family and domain databases

Gene3D3.30.2230.10. 2 hits.
3.30.40.10. 1 hit.
InterProIPR006615. Pept_C19_DUSP.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PfamPF06337. DUSP. 1 hit.
PF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]
SMARTSM00695. DUSP. 2 hits.
[Graphical view]
SUPFAMSSF143791. SSF143791. 2 hits.
PROSITEPS51283. 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]
ProtoNetSearch...

Other

NextBio370477.
PROQ8R5K2.
SOURCESearch...

Entry information

Entry nameUBP33_MOUSE
AccessionPrimary (citable) accession number: Q8R5K2
Secondary accession number(s): Q3UP32 expand/collapse secondary AC list , Q5FWK0, Q8K0I3, Q99K22
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 2009
Last sequence update: December 15, 2009
Last modified: July 9, 2014
This is version 86 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot