O88623 (UBP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase 2
EC=3.4.19.12

Alternative name(s):
41 kDa ubiquitin-specific protease
Deubiquitinating enzyme 2
Ubiquitin thioesterase 2
Ubiquitin-specific-processing protease 2

Gene names

Name:	Usp2
Synonyms:	Ubp41
ORF Names:	MNCb-0190

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	613 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1. Isoform 1 and isoform 2 possess both ubiquitin-specific peptidase and isopeptidase activities. Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity. Has no deubiquitinase activity against p53/TP53. Prevents MDM2-mediated degradation of MDM4. Plays a role in the G1/S cell-cycle progression in normal and cancer cells. Plays a role in the regulation of myogenic differentiation of embryonic muscle cells By similarity.
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).
Cofactor	Binds 1 zinc ion By similarity.
Enzyme regulation	Cleavage is inhibited by ubiquitin in a dosage-dependent manner. Cleavage is blocked by ubiquitin aldehyde By similarity.
Subunit structure	Found in trimeric complex with MDM2 and MDM4 and UPB2. Interacts with CCND1; the interaction is direct and promotes its stabilization by antagonizing ubiquitin-dependent degradation. Interacts (via N-terminus and C-terminus) with MDM2. Interacts with MDM4 By similarity. Homooligomer. Ref.1
Subcellular location	Cytoplasm. Cytoplasm › perinuclear region By similarity. Note: Localizes in the spermatid head in late-elongating spermatids in the thin area between the outer acrosomal membrane and the plasma membrane By similarity. Ref.1 Isoform 2: Nucleus By similarity Ref.1.
Tissue specificity	Isoform 1 is expressed in heart, liver, kidney, pancreas and to a lower extent in skeletal muscle, brain and testis (at protein level). Expressed in testis, brain, heart and skeletal muscle. Ref.1
Developmental stage	No stage-dependent developmental pattern of expression is detected. First detected throughout 7.5 dpc embryos. Ref.1
Domain	The different N-terminus extensions of isoform 1 and isoform 2 determine their respective subcellular localization and differentiel effect on myoblast fusion and accumulation of muscle-specific proteins. The different N-terminus extensions of isoform 1 and isoform 4 are not essential for their catalytic activity By similarity.
Sequence similarities	Belongs to the peptidase C19 family. USP2 subfamily.

Ontologies

Keywords
Biological process	Cell cycle Myogenesis Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW muscle organ development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of skeletal muscle tissue development Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of skeletal muscle tissue development Inferred from electronic annotation. Source: Compara protein deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB protein stabilization Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cell cortex Inferred from direct assay Ref.1. Source: MGI centrosome Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay Ref.1. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from direct assay Ref.1. Source: MGI
Molecular_function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW identical protein binding Inferred from direct assay Ref.1. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin thiolesterase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O88623-1)

Also known as: Usp2-69;

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: O88623-2)

Also known as: Usp2-45;

The sequence of this isoform differs from the canonical sequence as follows:
     1-217: Missing.
     218-266: VLTQAPPPSR...RSSSPGRDTM → MRTSYTVTLP...FVGLLLNKAK

Isoform 3 (identifier: O88623-3)

The sequence of this isoform differs from the canonical sequence as follows:
     154-154: L → LRTSDGY

Isoform 4 (identifier: O88623-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-220: Missing.
     221-268: QAPPPSRVPE...SSPGRDTMNS → MRTSYTVTLP...TFVGLLLNKA

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 613	613	Ubiquitin carboxyl-terminal hydrolase 2		PRO_0000080617
Regions
	Region	1 – 207	207	Necessary for interaction with MDM4 By similarity
	Region	411 – 511	101	Necessary for interaction with MDM4 By similarity
Sites
	Active site	284	1	Nucleophile By similarity
	Active site	565	1	Proton acceptor By similarity
	Metal binding	433	1	Zinc By similarity
	Metal binding	436	1	Zinc By similarity
	Metal binding	484	1	Zinc By similarity
	Metal binding	487	1	Zinc By similarity
Natural variations
	Alternative sequence	1 – 220	220	Missing in isoform 4.		VSP_020130
	Alternative sequence	1 – 217	217	Missing in isoform 2.		VSP_020131
	Alternative sequence	154	1	L → LRTSDGY in isoform 3.		VSP_020132
	Alternative sequence	218 – 266	49	VLTQA…GRDTM → MRTSYTVTLPEEPPAAHFPA LAKELRPRSPLSPSLLLSTF VGLLLNKAK in isoform 2.		VSP_020133
	Alternative sequence	221 – 268	48	QAPPP…DTMNS → MRTSYTVTLPEEPPAAHFPA LAKELRPRSPLSPSLLLSTF VGLLLNKA in isoform 4.		VSP_020134
Experimental info
Isoform 2:
	Sequence conflict	44	1	L → M in AAC28393. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Usp2-69) [UniParc]. Last modified September 5, 2006. Version 2. Checksum: 7B5DD3594A42C445	FASTA	613	68,845
	10 20 30 40 50 60 MSQLSSTLKR YTESSRYTDA PYAKPGYGTY TPSSYGANLA ASFLEKEKLG FKPVSPTSFL 70 80 90 100 110 120 PRPRTYGPSS ILDCDRGRPL LRSDIIGSSK RSESQTRGNE RPSGSGLNGG SGFSYGVSSN 130 140 150 160 170 180 SLSYLPMNAR DQGVTLSQKK SNSQSDLARD FSSLRTSDGY RTSEGFRIDP GNLGRSPMLA 190 200 210 220 230 240 RTRKELCALQ GLYQAASRSE YLTDYLENYG RKGSAPQVLT QAPPPSRVPE VLSPTYRPSG 250 260 270 280 290 300 RYTLWEKSKG QASGPSRSSS PGRDTMNSKS AQGLAGLRNL GNTCFMNSIL QCLSNTRELR 310 320 330 340 350 360 DYCLQRLYMR DLGHTSSAHT ALMEEFAKLI QTIWTSSPND VVSPSEFKTQ IQRYAPRFMG 370 380 390 400 410 420 YNQQDAQEFL RFLLDGLHNE VNRVAARPKA SPETLDHLPD EEKGRQMWRK YLEREDSRIG 430 440 450 460 470 480 DLFVGQLKSS LTCTDCGYCS TVFDPFWDLS LPIAKRGYPE VTLMDCMRLF TKEDILDGDE 490 500 510 520 530 540 KPTCCRCRAR KRCIKKFSVQ RFPKILVLHL KRFSESRIRT SKLTTFVNFP LRDLDLREFA 550 560 570 580 590 600 SENTNHAVYN LYAVSNHSGT TMGGHYTAYC RSPVTGEWHT FNDSSVTPMS SSQVRTSDAY 610 LLFYELASPP SRM
	Isoform 2 (Usp2-45) [UniParc]. Checksum: 14CC674DC08FFF93	FASTA	396	45,238
	10 20 30 40 50 60 MRTSYTVTLP EEPPAAHFPA LAKELRPRSP LSPSLLLSTF VGLLLNKAKN SKSAQGLAGL 70 80 90 100 110 120 RNLGNTCFMN SILQCLSNTR ELRDYCLQRL YMRDLGHTSS AHTALMEEFA KLIQTIWTSS 130 140 150 160 170 180 PNDVVSPSEF KTQIQRYAPR FMGYNQQDAQ EFLRFLLDGL HNEVNRVAAR PKASPETLDH 190 200 210 220 230 240 LPDEEKGRQM WRKYLEREDS RIGDLFVGQL KSSLTCTDCG YCSTVFDPFW DLSLPIAKRG 250 260 270 280 290 300 YPEVTLMDCM RLFTKEDILD GDEKPTCCRC RARKRCIKKF SVQRFPKILV LHLKRFSESR 310 320 330 340 350 360 IRTSKLTTFV NFPLRDLDLR EFASENTNHA VYNLYAVSNH SGTTMGGHYT AYCRSPVTGE 370 380 390 WHTFNDSSVT PMSSSQVRTS DAYLLFYELA SPPSRM
	Isoform 3 [UniParc]. Checksum: 93A6F2B9269316F8	FASTA	619	69,525
	10 20 30 40 50 60 MSQLSSTLKR YTESSRYTDA PYAKPGYGTY TPSSYGANLA ASFLEKEKLG FKPVSPTSFL 70 80 90 100 110 120 PRPRTYGPSS ILDCDRGRPL LRSDIIGSSK RSESQTRGNE RPSGSGLNGG SGFSYGVSSN 130 140 150 160 170 180 SLSYLPMNAR DQGVTLSQKK SNSQSDLARD FSSLRTSDGY RTSDGYRTSE GFRIDPGNLG 190 200 210 220 230 240 RSPMLARTRK ELCALQGLYQ AASRSEYLTD YLENYGRKGS APQVLTQAPP PSRVPEVLSP 250 260 270 280 290 300 TYRPSGRYTL WEKSKGQASG PSRSSSPGRD TMNSKSAQGL AGLRNLGNTC FMNSILQCLS 310 320 330 340 350 360 NTRELRDYCL QRLYMRDLGH TSSAHTALME EFAKLIQTIW TSSPNDVVSP SEFKTQIQRY 370 380 390 400 410 420 APRFMGYNQQ DAQEFLRFLL DGLHNEVNRV AARPKASPET LDHLPDEEKG RQMWRKYLER 430 440 450 460 470 480 EDSRIGDLFV GQLKSSLTCT DCGYCSTVFD PFWDLSLPIA KRGYPEVTLM DCMRLFTKED 490 500 510 520 530 540 ILDGDEKPTC CRCRARKRCI KKFSVQRFPK ILVLHLKRFS ESRIRTSKLT TFVNFPLRDL 550 560 570 580 590 600 DLREFASENT NHAVYNLYAV SNHSGTTMGG HYTAYCRSPV TGEWHTFNDS SVTPMSSSQV 610 RTSDAYLLFY ELASPPSRM
	Isoform 4 [UniParc]. Checksum: F4715ABDE436573B	FASTA	393	44,908
	10 20 30 40 50 60 MRTSYTVTLP EEPPAAHFPA LAKELRPRSP LSPSLLLSTF VGLLLNKAKS AQGLAGLRNL 70 80 90 100 110 120 GNTCFMNSIL QCLSNTRELR DYCLQRLYMR DLGHTSSAHT ALMEEFAKLI QTIWTSSPND 130 140 150 160 170 180 VVSPSEFKTQ IQRYAPRFMG YNQQDAQEFL RFLLDGLHNE VNRVAARPKA SPETLDHLPD 190 200 210 220 230 240 EEKGRQMWRK YLEREDSRIG DLFVGQLKSS LTCTDCGYCS TVFDPFWDLS LPIAKRGYPE 250 260 270 280 290 300 VTLMDCMRLF TKEDILDGDE KPTCCRCRAR KRCIKKFSVQ RFPKILVLHL KRFSESRIRT 310 320 330 340 350 360 SKLTTFVNFP LRDLDLREFA SENTNHAVYN LYAVSNHSGT TMGGHYTAYC RSPVTGEWHT 370 380 390 FNDSSVTPMS SSQVRTSDAY LLFYELASPP SRM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gene structure, alternate splicing, tissue distribution, cellular localization, and developmental expression pattern of mouse deubiquitinating enzyme isoforms Usp2-45 and Usp2-69." Gousseva N., Baker R.T. Gene Expr. 11:163-179(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, SUBUNIT. Strain: C57BL/6. Tissue: Kidney and Retina.
[2]	"Isolation of full-length cDNA clones from mouse brain cDNA library made by oligo-capping method." Osada N., Kusuda J., Tanuma R., Ito A., Hirata M., Sugano S., Hashimoto K. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Strain: C57BL/6. Tissue: Brain.
[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] (ISOFORM 3). Strain: C57BL/6J. Tissue: Thymus.
[4]	"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 3). Strain: C57BL/6. Tissue: Retina.
[5]	"Cloning and expression of the human and mouse UBP41." Gong L., Yeh E.T.H. Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 261-613 (ISOFORM 2). Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY255637 mRNA. Translation: AAQ83301.1. AY255638 mRNA. Translation: AAQ83302.1. AY255639 mRNA. Translation: AAQ83303.1. AY255640 mRNA. Translation: AAQ83304.1. AB041799 mRNA. Translation: BAA95110.1. AK138799 mRNA. Translation: BAE23782.1. BC017517 mRNA. Translation: AAH17517.1. AF079565 mRNA. Translation: AAC28393.1.
IPI	IPI00377286. IPI00409197. IPI00785316. IPI00785464.
RefSeq	NP_058088.2. NM_016808.2. NP_932759.1. NM_198091.2. NP_932760.2. NM_198092.2.
UniGene	Mm.272770.
3D structure databases
ProteinModelPortal	O88623.
SMR	O88623. Positions 271-608.
ModBase	Search...
Protein family/group databases
MEROPS	C19.013.
PTM databases
PhosphoSite	O88623.
Proteomic databases
PRIDE	O88623.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000034508; ENSMUSP00000034508; ENSMUSG00000032010. ENSMUST00000065461; ENSMUSP00000070264; ENSMUSG00000032010. ENSMUST00000114830; ENSMUSP00000110479; ENSMUSG00000032010. ENSMUST00000176416; ENSMUSP00000135482; ENSMUSG00000032010. ENSMUST00000177054; ENSMUSP00000135018; ENSMUSG00000032010.
GeneID	53376.
KEGG	mmu:53376.
UCSC	uc009pbn.1. mouse. uc009pbp.1. mouse. uc012grp.1. mouse.
Organism-specific databases
CTD	9099.
MGI	MGI:1858178. Usp2.
Phylogenomic databases
eggNOG	COG5533.
GeneTree	ENSGT00670000098024.
HOGENOM	HOG000231498.
HOVERGEN	HBG011164.
InParanoid	O88623.
KO	K11833.
OMA	SASHRSY.
OrthoDB	EOG47M1XH.
Gene expression databases
ArrayExpress	O88623.
Bgee	O88623.
CleanEx	MM_USP2.
Genevestigator	O88623.
GermOnline	ENSMUSG00000032010. Mus musculus.
Family and domain databases
InterPro	IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. [Graphical view]
Pfam	PF00443. UCH. 1 hit. [Graphical view]
PROSITE	PS00972. UCH_2_1. 1 hit. PS00973. UCH_2_2. 1 hit. PS50235. UCH_2_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	310185.
SOURCE	Search...

Entry information

Entry name

UBP2_MOUSE

Accession

Primary (citable) accession number: O88623
Secondary accession number(s): Q6X4T9 , Q6X4U1, Q8VD74, Q9JJ87

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	September 5, 2006
Last modified:	May 1, 2013
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program