Q8R5K2 (UBP33_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Usp33
Synonyms:	Vdu1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	909 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Cytoplasm › perinuclear region By similarity. Cytoplasm › cytoskeleton › centrosome 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.
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 process	Endocytosis Ubl conjugation pathway
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Inferred from mutant phenotype Ref.5. Source: UniProtKB cell migration Inferred from mutant phenotype Ref.5. 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 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_component	cell body Inferred from direct assay Ref.4. Source: MGI perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	cysteine-type endopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin thiolesterase activity Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-specific protease activity Inferred from sequence alignment Ref.1. Source: MGI 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 909	909	Ubiquitin carboxyl-terminal hydrolase 33		PRO_0000390424
Regions
	Domain	684 – 777	94	DUSP 1
	Domain	785 – 888	104	DUSP 2
	Zinc finger	28 – 92	65	UBP-type
Sites
	Active site	163	1	Nucleophile By similarity
	Active site	640	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	407	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	519 – 526	8	Missing in isoform 2.		VSP_038531
Experimental info
	Sequence conflict	309	1	P → S in AAL78316. Ref.1
	Sequence conflict	411	1	L → P in AAL78316. Ref.1
	Sequence conflict	411	1	L → P in AAH05506. Ref.2
	Sequence conflict	465	1	I → V in AAL78316. Ref.1
	Sequence conflict	465	1	I → V in AAH05506. Ref.2
	Sequence conflict	779	1	T → S in AAH89315. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 15, 2009. Version 2. Checksum: F8A2BDA9FBCD633A	FASTA	909	102,728
	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
	Isoform 2 [UniParc]. Checksum: 6154729A27ED06BE	FASTA	901	101,839
	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 AFFMEYVKSW FWGPVVTLQD CLAAFFARDE 550 560 570 580 590 600 LKGDNMYSCE KCKKLRNGVK FCKVQKFPEI LCIHLKRFRH ELMFSTKIST HVSFPLEGLD 610 620 630 640 650 660 LQPFLAKDSP AQIVTYDLLS VICHHGTASS GHYIAYCRNN LNNLWYEFDD QSVTEVSEST 670 680 690 700 710 720 VQNAEAYVLF YRKSSEEAQK ERRRISNLLN IMEPSLLQFY ISRQWLNKFK TFAEPGPISN 730 740 750 760 770 780 NDFLCIHGGI PPRKASYIED LVLMLPQNIW DNLYSRYGGG PAVNHLYICH TCQIELEKIE 790 800 810 820 830 840 KRRKTELEIF IRLNRAFQEE DSPATFYCIS MQWFREWESF VKGKDGDPPG PIDNTKIAVT 850 860 870 880 890 900 KCGSVMLKQG ADSGQISEET WNFLQSIYGG GPEVILRPPV VHVDPDVLQA EEKIEVETRS L

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00319995. IPI00798461.
RefSeq	NP_001239415.1. NM_001252486.1. NP_573510.2. NM_133247.3.
UniGene	Mm.258320.
3D structure databases
ProteinModelPortal	Q8R5K2.
SMR	Q8R5K2. Positions 5-392, 413-683.
ModBase	Search...
Protein family/group databases
MEROPS	C19.037.
PTM databases
PhosphoSite	Q8R5K2.
Proteomic databases
PaxDb	Q8R5K2.
PRIDE	Q8R5K2.
Protocols and materials databases
DNASU	170822.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000026507; ENSMUSP00000026507; ENSMUSG00000025437. ENSMUST00000117492; ENSMUSP00000113265; ENSMUSG00000025437.
GeneID	170822.
KEGG	mmu:170822.
UCSC	uc008rti.2. mouse. uc008rtj.2. mouse.
Organism-specific databases
CTD	23032.
MGI	MGI:2159711. Usp33.
Phylogenomic databases
eggNOG	COG5560.
GeneTree	ENSGT00690000101718.
HOGENOM	HOG000286031.
HOVERGEN	HBG054196.
InParanoid	Q8R5K2.
KO	K11848.
OMA	TMEEDKS.
OrthoDB	EOG4B8JC9.
Gene expression databases
ArrayExpress	Q8R5K2.
Bgee	Q8R5K2.
Genevestigator	Q8R5K2.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR006615. Pept_C19_DUSP. IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. IPR013083. Znf_RING/FYVE/PHD. IPR001607. Znf_UBP. [Graphical view]
Pfam	PF06337. DUSP. 1 hit. PF00443. UCH. 1 hit. PF02148. zf-UBP. 1 hit. [Graphical view]
SMART	SM00695. DUSP. 2 hits. [Graphical view]
PROSITE	PS51283. DUSP. 2 hits. PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. PS50271. ZF_UBP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	370477.
SOURCE	Search...

Entry information

Entry name

UBP33_MOUSE

Accession

Primary (citable) accession number: Q8R5K2
Secondary accession number(s): Q3UP32 , Q5FWK0, Q8K0I3, Q99K22

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 2009
Last sequence update:	December 15, 2009
Last modified:	May 29, 2013
This is version 74 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program