Q5U349 (UBP2_RAT) 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
Ubiquitin-specific-processing protease testis
Short name=UBP-t

Gene names

Name:	Usp2
Synonyms:	Ubp41, Ubp69

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

Protein attributes

Sequence length	618 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. 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 By similarity. Isoform 1 and isoform 2 possess both ubiquitin-specific peptidase and isopeptidase activities. Plays a role in the regulation of myogenic differentiation of embryonic muscle cells. Ref.1 Ref.2
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 By similarity. Cleavage is blocked by ubiquitin aldehyde. Ref.1
Subunit structure	Homooligomer. 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.
Subcellular location	Cytoplasm By similarity Ref.2. Isoform 1: Cytoplasm › perinuclear region. Note: Localizes in the spermatid head in late-elongating spermatids in the thin area between the outer acrosomal membrane and the plasma membrane. Ref.2 Isoform 2: Nucleus Ref.2.
Tissue specificity	Expressed in mesangial cells of the kidney. Isoform 1 and isoform 2 are expressed in elongated spermatids; the shorter form appearing earlier than the longer form (at protein level). Isoform 1 and isoform 2 are expressed in early round spermatids of the testis. Isoform 1 is expressed in muscle and heart. Isoform 2 is expressed in muscle, lung, heart, brain, liver and ovary. During muscle differentiaition, isoform 1 expression increases before the onset of membrane fusion and decreases as the myogenic processes proceeded; un counterpart, isoform 2 expression remains low until the burst of membrane fusion but increases thereafter. Ref.1 Ref.2 Ref.5
Induction	Up-regulated by IL-1. Isoform 1 is up-regulated with any signal for withdrawal from the cell cycle such as serum deprivation. Ref.1 Ref.2 Ref.5
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 2 are not essential for their catalytic activity.
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 direct assay Ref.1. Source: UniProtKB 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 direct assay Ref.1. Source: UniProtKB protein deubiquitination Inferred from direct assay Ref.1. 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 electronic annotation. Source: Compara centrosome Inferred from direct assay Ref.1. Source: RGD nucleus Inferred from direct assay Ref.1. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin thiolesterase activity Inferred from mutant phenotype Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5U349-1)

Also known as: Ubp69; Ubp-t2;

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.

Note: Stimulates both membrane fusion during myogenesis and accumulation of muscle-specific proteins.

Isoform 2 (identifier: Q5U349-2)

Also known as: Ubp45; Ubp-t1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-271: MSQLSSTLKR...RSTSPGRDTM → MRTSYTVTLP...FVGLLLNKAK

Note: Inhibits both membrane fusion during myogenesis and accumulation of muscle-specific proteins.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 618	618	Ubiquitin carboxyl-terminal hydrolase 2		PRO_0000395966
Regions
	Region	1 – 213	213	Necessary for interaction with MDM4 By similarity
	Region	416 – 516	101	Necessary for interaction with MDM4 By similarity
Sites
	Active site	289	1	Nucleophile
	Active site	570	1	Proton acceptor By similarity
	Metal binding	438	1	Zinc By similarity
	Metal binding	441	1	Zinc By similarity
	Metal binding	489	1	Zinc By similarity
	Metal binding	492	1	Zinc By similarity
Natural variations
	Alternative sequence	1 – 271	271	MSQLS…GRDTM → MRTSYTVTLPEEPPAAPFPA LAKELRPRSPLSPSLLLSTF VGLLLNKAK in isoform 2.		VSP_039561
Experimental info
	Mutagenesis	289	1	C → S: Loss of enzymatic activity. Reduces both membrane fusion during myogenesis and accumulation of muscle-specific proteins. Ref.2
	Sequence conflict	172	1	F → S in AAF17574. Ref.1
	Sequence conflict	202	1	A → T in AAF14190. Ref.2
	Sequence conflict	260	1	P → A in AAF17574. Ref.1
	Sequence conflict	607	1	L → F in AAF14189. Ref.2
	Sequence conflict	607	1	L → F in AAF14190. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Ubp69) (Ubp-t2) [UniParc]. Last modified December 7, 2004. Version 1. Checksum: B8B2091192CA4944	FASTA	618	69,363
	10 20 30 40 50 60 MSQLSSTLKR YTESSRYTDA PYAKSGYGTY TPSSYGANLA ASFLEKEKLG FKPVSPTSFL 70 80 90 100 110 120 PRPRTYGPSS ILDCDRGRPL LRSDITGGSK RSESQTRGNE RPSGSGLNGG SGFPYGVTSN 130 140 150 160 170 180 SLSYLPMNAR DQGVTLGQKK SNSQSDLARD FSSLRTSDSY RTSDGYRASD GFRIDPGNLG 190 200 210 220 230 240 RSPMLARTRK ELCALQGLYQ AASRSEYLTD YLENYGRKGS APQVLTQAPP SRVPEVLSPT 250 260 270 280 290 300 YRPSGRYTLW EKNKGQASGP SRSTSPGRDT MNSKSAQGLA GLRNLGNTCF MNSILQCLSN 310 320 330 340 350 360 TRELRDYCLQ RLYMRDLGHT SSAHTALMEE FAKLIQTIWT SSPNDVVSPS EFKTQIQRYA 370 380 390 400 410 420 PRFVGYNQQD AQEFLRFLLD GLHNEVNRVA ARPKPSPESL DHLPDEEKGR QMWRKYLERE 430 440 450 460 470 480 DSRIGDLFVG QLKSSLTCTD CGYCSTVFDP FWDLSLPIAK RGYPEVTLMD CMRLFTKEDV 490 500 510 520 530 540 LDGDEKPTCC RCRARKRCIK KFSVQRFPKI LVLHLKRFSE SRIRTSKLTT FVNFPLRDLD 550 560 570 580 590 600 LREFASENTN HAVYNLYAVS NHSGTTMGGH YTAYCRSPVT GEWHTFNDSS VTPMSSSQVR 610 TSDAYLLFYE LASPPSRM
	Isoform 2 (Ubp45) (Ubp-t1) [UniParc]. Checksum: ED7C91FB5A0964E3	FASTA	396	45,164
	10 20 30 40 50 60 MRTSYTVTLP EEPPAAPFPA LAKELRPRSP LSPSLLLSTF VGLLLNKAKN SKSAQGLAGL 70 80 90 100 110 120 RNLGNTCFMN SILQCLSNTR ELRDYCLQRL YMRDLGHTSS AHTALMEEFA KLIQTIWTSS 130 140 150 160 170 180 PNDVVSPSEF KTQIQRYAPR FVGYNQQDAQ EFLRFLLDGL HNEVNRVAAR PKPSPESLDH 190 200 210 220 230 240 LPDEEKGRQM WRKYLEREDS RIGDLFVGQL KSSLTCTDCG YCSTVFDPFW DLSLPIAKRG 250 260 270 280 290 300 YPEVTLMDCM RLFTKEDVLD GDEKPTCCRC RARKRCIKKF SVQRFPKILV LHLKRFSESR 310 320 330 340 350 360 IRTSKLTTFV NFPLRDLDLR EFASENTNHA VYNLYAVSNH SGTTMGGHYT AYCRSPVTGE 370 380 390 WHTFNDSSVT PMSSSQVRTS DAYLLFYELA SPPSRM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Divergent N-terminal sequences target an inducible testis deubiquitinating enzyme to distinct subcellular structures." Lin H., Keriel A., Morales C.R., Bedard N., Zhao Q., Hingamp P., Lefrancois S., Combaret L., Wing S.S. Mol. Cell. Biol. 20:6568-6578(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY. Tissue: Testis.
[2]	"Antagonistic regulation of myogenesis by two deubiquitinating enzymes, UBP45 and UBP69." Park K.C., Kim J.H., Choi E.J., Min S.W., Rhee S., Baek S.H., Chung S.S., Bang O., Park D., Chiba T., Tanaka K., Chung C.H. Proc. Natl. Acad. Sci. U.S.A. 99:9733-9738(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION, INDUCTION, MUTAGENESIS OF CYS-289, TISSUE SPECIFICITY. Tissue: Skeletal muscle.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[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 1). Tissue: Heart.
[5]	"Expression of USP2-69 in mesangial cells in vivo and in vitro." Wang S., Wu H., Liu Y., Sun J., Zhao Z., Chen Q., Guo M., Ma D., Zhang Z. Pathol. Int. 60:184-192(2010) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION BY IL-1.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF202453 mRNA. Translation: AAF17574.1. AF202454 mRNA. Translation: AAF17575.1. AF106658 mRNA. Translation: AAF14189.1. AF106659 mRNA. Translation: AAF14190.1. CH473975 Genomic DNA. Translation: EDL95274.1. CH473975 Genomic DNA. Translation: EDL95276.1. CH473975 Genomic DNA. Translation: EDL95277.1. BC085719 mRNA. Translation: AAH85719.1.
IPI	IPI00213304. IPI00213307.
RefSeq	NP_446226.2. NM_053774.2.
UniGene	Rn.203590.
3D structure databases
HSSP	HSSP built from PDB template 1NBF based on UniProtKB Q93009.
ProteinModelPortal	Q5U349.
SMR	Q5U349. Positions 276-613.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48683N.
STRING	10116.ENSRNOP00000009975.
Protein family/group databases
MEROPS	C19.013.
Proteomic databases
PaxDb	Q5U349.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000009975; ENSRNOP00000009975; ENSRNOG00000006663. ENSRNOT00000036051; ENSRNOP00000030257; ENSRNOG00000006663.
GeneID	115771.
KEGG	rno:115771.
UCSC	RGD:621073. rat.
Organism-specific databases
CTD	9099.
RGD	621073. Usp2.
Phylogenomic databases
eggNOG	COG5533.
GeneTree	ENSGT00670000098024.
HOGENOM	HOG000231498.
HOVERGEN	HBG011164.
InParanoid	Q9R083.
KO	K11833.
OMA	SASHRSY.
OrthoDB	EOG47M1XH.
Gene expression databases
ArrayExpress	Q5U349.
Genevestigator	Q5U349.
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	618951.

Entry information

Entry name

UBP2_RAT

Accession

Primary (citable) accession number: Q5U349
Secondary accession number(s): Q9QXL3 , Q9QXL4, Q9R083, Q9R084

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 10, 2010
Last sequence update:	December 7, 2004
Last modified:	April 3, 2013
This is version 60 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program