Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProtKB - O75604 (UBP2_HUMAN)

Protein

Ubiquitin carboxyl-terminal hydrolase 2

Gene

USP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1 (PubMed:17290220, PubMed:19917254, PubMed:19838211). Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities (By similarity). Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity (PubMed:17290220, PubMed:19838211). Has no deubiquitinase activity against p53/TP53 (PubMed:17290220). Prevents MDM2-mediated degradation of MDM4 (PubMed:17290220). Plays a role in the G1/S cell-cycle progression in normal and cancer cells (PubMed:19917254). Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (By similarity). Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability (By similarity). Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and ARNTL/BMAL1 (By similarity). Plays a role in the regulation of myogenic differentiation of embryonic muscle cells (By similarity).By similarity3 Publications
Isoform 4: Circadian clock output effector that regulates Ca2+ absorption in the small intestine. Probably functions by regulating protein levels of the membrane scaffold protein NHERF4 in a rhythmic manner, and is therefore likely to control Ca2+ membrane permeability mediated by the Ca2+ channel TRPV6 in the intestine.By similarity

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).

Activity regulationi

Cleavage is inhibited by ubiquitin in a dosage-dependent manner. Cleavage is blocked by ubiquitin aldehyde.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei276NucleophilePROSITE-ProRule annotation1
Metal bindingi425Zinc1 Publication1
Metal bindingi428Zinc1 Publication1
Metal bindingi476Zinc1 Publication1
Metal bindingi479Zinc1 Publication1
Active sitei557Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • cyclin binding Source: UniProtKB
  • cysteine-type endopeptidase activity Source: ProtInc
  • identical protein binding Source: Ensembl
  • metal ion binding Source: UniProtKB-KW
  • thiol-dependent ubiquitin-specific protease activity Source: FlyBase
  • thiol-dependent ubiquitinyl hydrolase activity Source: Reactome
  • ubiquitin protein ligase binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processBiological rhythms, Cell cycle, Myogenesis, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5689880 Ub-specific processing proteases
R-HSA-6804757 Regulation of TP53 Degradation

Protein family/group databases

MEROPSiC19.013
MoonDBiO75604 Predicted

Names & Taxonomyi

Protein namesi
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 namesi
Name:USP2
Synonyms:UBP41
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000036672.15
HGNCiHGNC:12618 USP2
MIMi604725 gene
neXtProtiNX_O75604

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, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi276C → A: Loss of enzymatic activity. Increases the steady-state level of CCND1. 1 Publication1
Mutagenesisi549H → A: Loss of enzymatic activity. Increases the steady-state level of MDM2 and MDM4 that leads to attenuation of MDM2-mediated degradation of p53/TP53 and MDM4. Increases the level of p53/TP53 and MDM4 ubiquitin conjugates. 2 Publications1

Organism-specific databases

DisGeNETi9099
OpenTargetsiENSG00000036672
PharmGKBiPA37244

Chemistry databases

ChEMBLiCHEMBL1293227

Polymorphism and mutation databases

BioMutaiUSP2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806161 – 605Ubiquitin carboxyl-terminal hydrolase 2Add BLAST605

Proteomic databases

MaxQBiO75604
PaxDbiO75604
PeptideAtlasiO75604
PRIDEiO75604
ProteomicsDBi50112
50113 [O75604-2]
50114 [O75604-3]
50115 [O75604-4]

PTM databases

iPTMnetiO75604
PhosphoSitePlusiO75604

Expressioni

Tissue specificityi

Expressed in mesangial cells of the kidney and in different types of glomerulonephritides (at protein level).1 Publication

Inductioni

Down-regulated by cisplatin (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000036672 Expressed in 183 organ(s), highest expression level in muscle of leg
CleanExiHS_USP2
ExpressionAtlasiO75604 baseline and differential
GenevisibleiO75604 HS

Organism-specific databases

HPAiHPA006777
HPA007222

Interactioni

Subunit structurei

Homooligomer (By similarity). Found in trimeric complex with MDM2 and MDM4 and USP2. 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. Interacts with PER1 (By similarity). Interacts with KCNQ1; counteracts the NEDD4L-specific down-regulation of I(Ks) and restore plasma membrane localization of KCNQ1 (PubMed:22024150). Isoform 4: Interacts with PDZD3 and CLTC (By similarity).By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi114553, 109 interactors
CORUMiO75604
DIPiDIP-29134N
IntActiO75604, 116 interactors
MINTiO75604
STRINGi9606.ENSP00000260187

Chemistry databases

BindingDBiO75604

Structurei

Secondary structure

1605
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO75604
SMRiO75604
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75604

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini267 – 599USPAdd BLAST333

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 200Necessary for interaction with MDM41 PublicationAdd BLAST200
Regioni403 – 503Necessary for interaction with MDM41 PublicationAdd BLAST101

Domaini

The different N-terminus extensions of isoform 1 and isoform 4 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 similaritiesi

Belongs to the peptidase C19 family. USP2 subfamily.Curated

Phylogenomic databases

eggNOGiKOG1868 Eukaryota
ENOG410XP8T LUCA
GeneTreeiENSGT00860000133682
HOGENOMiHOG000231498
HOVERGENiHBG011164
InParanoidiO75604
KOiK11833
OMAiCLSNTKP
OrthoDBiEOG091G0120
PhylomeDBiO75604
TreeFamiTF106277

Family and domain databases

InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00443 UCH, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O75604-1) [UniParc]FASTAAdd to basket
Also known as: USP2a, 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.

« Hide
        10         20         30         40         50
MSQLSSTLKR YTESARYTDA HYAKSGYGAY TPSSYGANLA ASLLEKEKLG 
        60         70         80         90        100
FKPVPTSSFL TRPRTYGPSS LLDYDRGRPL LRPDITGGGK RAESQTRGTE 
       110        120        130        140        150
RPLGSGLSGG SGFPYGVTNN CLSYLPINAY DQGVTLTQKL DSQSDLARDF 
       160        170        180        190        200
SSLRTSDSYR IDPRNLGRSP MLARTRKELC TLQGLYQTAS CPEYLVDYLE 
       210        220        230        240        250
NYGRKGSASQ VPSQAPPSRV PEIISPTYRP IGRYTLWETG KGQAPGPSRS 
       260        270        280        290        300
SSPGRDGMNS KSAQGLAGLR NLGNTCFMNS ILQCLSNTRE LRDYCLQRLY 
       310        320        330        340        350
MRDLHHGSNA HTALVEEFAK LIQTIWTSSP NDVVSPSEFK TQIQRYAPRF 
       360        370        380        390        400
VGYNQQDAQE FLRFLLDGLH NEVNRVTLRP KSNPENLDHL PDDEKGRQMW 
       410        420        430        440        450
RKYLEREDSR IGDLFVGQLK SSLTCTDCGY CSTVFDPFWD LSLPIAKRGY 
       460        470        480        490        500
PEVTLMDCMR LFTKEDVLDG DEKPTCCRCR GRKRCIKKFS IQRFPKILVL 
       510        520        530        540        550
HLKRFSESRI RTSKLTTFVN FPLRDLDLRE FASENTNHAV YNLYAVSNHS 
       560        570        580        590        600
GTTMGGHYTA YCRSPGTGEW HTFNDSSVTP MSSSQVRTSD AYLLFYELAS 

PPSRM
Length:605
Mass (Da):68,072
Last modified:March 27, 2002 - v2
Checksum:iAFF4DA9344D21812
GO
Isoform 2 (identifier: O75604-2) [UniParc]FASTAAdd to basket
Also known as: USP2b

The sequence of this isoform differs from the canonical sequence as follows:
     1-252: Missing.
     253-258: PGRDGM → MLNKAK

Note: No experimental confirmation available.
Show »
Length:353
Mass (Da):40,638
Checksum:i7CDF2F9A300B864F
GO
Isoform 3 (identifier: O75604-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-258: MSQLSSTLKR...RSSSPGRDGM → MLVPGSTRPYSKKRQ

Show »
Length:362
Mass (Da):41,682
Checksum:i5C93CA5F03D43293
GO
Isoform 4 (identifier: O75604-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-258: MSQLSSTLKR...RSSSPGRDGM → MRTSYTVTLP...FVGLLLNKAK

Show »
Length:396
Mass (Da):45,241
Checksum:i2A5B0403419F0655
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PJ34E9PJ34_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP2
137Annotation score:
E9PSH6E9PSH6_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP2
167Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti421S → G in BAB71388 (PubMed:14702039).Curated1
Sequence conflicti501H → R in BAB71388 (PubMed:14702039).Curated1
Sequence conflicti594L → H in AAC28392 (Ref. 1) Curated1
Sequence conflicti602 – 605PSRM → TSPI in AAC28392 (Ref. 1) Curated4
Isoform 3 (identifier: O75604-3)
Sequence conflicti10Y → S in AAH41366 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051519174R → Q. Corresponds to variant dbSNP:rs33929148Ensembl.1
Natural variantiVAR_051520383N → S. Corresponds to variant dbSNP:rs45533837Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0395591 – 258MSQLS…GRDGM → MLVPGSTRPYSKKRQ in isoform 3. 1 PublicationAdd BLAST258
Alternative sequenceiVSP_0395601 – 258MSQLS…GRDGM → MRTSYTVTLPEDPPAAPFPA LAKELRPRSPLSPSLLLSTF VGLLLNKAK in isoform 4. 2 PublicationsAdd BLAST258
Alternative sequenceiVSP_0052561 – 252Missing in isoform 2. 1 PublicationAdd BLAST252
Alternative sequenceiVSP_005257253 – 258PGRDGM → MLNKAK in isoform 2. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF079564 mRNA Translation: AAC28392.1
AF440755 mRNA Translation: AAN65363.1
AK057225 mRNA Translation: BAB71388.1
AK292255 mRNA Translation: BAF84944.1
EF445044 Genomic DNA Translation: ACA06096.1
EF445044 Genomic DNA Translation: ACA06097.1
AP003396 Genomic DNA No translation available.
CH471065 Genomic DNA Translation: EAW67484.1
CH471065 Genomic DNA Translation: EAW67485.1
CH471065 Genomic DNA Translation: EAW67486.1
BC002854 mRNA Translation: AAH02854.1
BC002955 mRNA Translation: AAH02955.1
BC041366 mRNA Translation: AAH41366.1
CCDSiCCDS58189.1 [O75604-3]
CCDS8422.1 [O75604-1]
CCDS8423.1 [O75604-4]
RefSeqiNP_001230688.1, NM_001243759.1 [O75604-3]
NP_004196.4, NM_004205.4 [O75604-1]
NP_741994.1, NM_171997.2 [O75604-4]
XP_005271778.1, XM_005271721.4 [O75604-1]
XP_005271779.1, XM_005271722.2 [O75604-1]
UniGeneiHs.524085

Genome annotation databases

EnsembliENST00000260187; ENSP00000260187; ENSG00000036672 [O75604-1]
ENST00000455332; ENSP00000407842; ENSG00000036672 [O75604-3]
ENST00000525735; ENSP00000436952; ENSG00000036672 [O75604-4]
GeneIDi9099
KEGGihsa:9099
UCSCiuc001pwl.5 human [O75604-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF079564 mRNA Translation: AAC28392.1
AF440755 mRNA Translation: AAN65363.1
AK057225 mRNA Translation: BAB71388.1
AK292255 mRNA Translation: BAF84944.1
EF445044 Genomic DNA Translation: ACA06096.1
EF445044 Genomic DNA Translation: ACA06097.1
AP003396 Genomic DNA No translation available.
CH471065 Genomic DNA Translation: EAW67484.1
CH471065 Genomic DNA Translation: EAW67485.1
CH471065 Genomic DNA Translation: EAW67486.1
BC002854 mRNA Translation: AAH02854.1
BC002955 mRNA Translation: AAH02955.1
BC041366 mRNA Translation: AAH41366.1
CCDSiCCDS58189.1 [O75604-3]
CCDS8422.1 [O75604-1]
CCDS8423.1 [O75604-4]
RefSeqiNP_001230688.1, NM_001243759.1 [O75604-3]
NP_004196.4, NM_004205.4 [O75604-1]
NP_741994.1, NM_171997.2 [O75604-4]
XP_005271778.1, XM_005271721.4 [O75604-1]
XP_005271779.1, XM_005271722.2 [O75604-1]
UniGeneiHs.524085

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HD5X-ray1.85A258-605[»]
2IBIX-ray2.20A251-605[»]
3NHEX-ray1.26A258-605[»]
3V6CX-ray1.70A258-605[»]
3V6EX-ray2.10A258-605[»]
5XU8X-ray1.81A258-605[»]
5XVEX-ray1.24A258-605[»]
ProteinModelPortaliO75604
SMRiO75604
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114553, 109 interactors
CORUMiO75604
DIPiDIP-29134N
IntActiO75604, 116 interactors
MINTiO75604
STRINGi9606.ENSP00000260187

Chemistry databases

BindingDBiO75604
ChEMBLiCHEMBL1293227

Protein family/group databases

MEROPSiC19.013
MoonDBiO75604 Predicted

PTM databases

iPTMnetiO75604
PhosphoSitePlusiO75604

Polymorphism and mutation databases

BioMutaiUSP2

Proteomic databases

MaxQBiO75604
PaxDbiO75604
PeptideAtlasiO75604
PRIDEiO75604
ProteomicsDBi50112
50113 [O75604-2]
50114 [O75604-3]
50115 [O75604-4]

Protocols and materials databases

DNASUi9099
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000260187; ENSP00000260187; ENSG00000036672 [O75604-1]
ENST00000455332; ENSP00000407842; ENSG00000036672 [O75604-3]
ENST00000525735; ENSP00000436952; ENSG00000036672 [O75604-4]
GeneIDi9099
KEGGihsa:9099
UCSCiuc001pwl.5 human [O75604-1]

Organism-specific databases

CTDi9099
DisGeNETi9099
EuPathDBiHostDB:ENSG00000036672.15
GeneCardsiUSP2
HGNCiHGNC:12618 USP2
HPAiHPA006777
HPA007222
MIMi604725 gene
neXtProtiNX_O75604
OpenTargetsiENSG00000036672
PharmGKBiPA37244
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1868 Eukaryota
ENOG410XP8T LUCA
GeneTreeiENSGT00860000133682
HOGENOMiHOG000231498
HOVERGENiHBG011164
InParanoidiO75604
KOiK11833
OMAiCLSNTKP
OrthoDBiEOG091G0120
PhylomeDBiO75604
TreeFamiTF106277

Enzyme and pathway databases

ReactomeiR-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5689880 Ub-specific processing proteases
R-HSA-6804757 Regulation of TP53 Degradation

Miscellaneous databases

ChiTaRSiUSP2 human
EvolutionaryTraceiO75604
GeneWikiiUSP2
GenomeRNAii9099
PROiPR:O75604
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000036672 Expressed in 183 organ(s), highest expression level in muscle of leg
CleanExiHS_USP2
ExpressionAtlasiO75604 baseline and differential
GenevisibleiO75604 HS

Family and domain databases

InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00443 UCH, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBP2_HUMAN
AccessioniPrimary (citable) accession number: O75604
Secondary accession number(s): B0YJB8
, E9PPM2, Q8IUM2, Q8IW04, Q96MB9, Q9BQ21
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: March 27, 2002
Last modified: November 7, 2018
This is version 174 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again