UniProtKB - O75604 (UBP2_HUMAN)
Ubiquitin carboxyl-terminal hydrolase 2
USP2
Functioni
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). EC:3.4.19.12
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 276 | NucleophilePROSITE-ProRule annotation | 1 | |
Metal bindingi | 425 | Zinc1 Publication | 1 | |
Metal bindingi | 428 | Zinc1 Publication | 1 | |
Metal bindingi | 476 | Zinc1 Publication | 1 | |
Metal bindingi | 479 | Zinc1 Publication | 1 | |
Active sitei | 557 | Proton acceptorPROSITE-ProRule annotation | 1 |
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
- ubiquitin protein ligase binding Source: UniProtKB
GO - Biological processi
- cell cycle Source: UniProtKB-KW
- circadian behavior Source: UniProtKB
- circadian regulation of gene expression Source: UniProtKB
- entrainment of circadian clock by photoperiod Source: UniProtKB
- locomotor rhythm Source: UniProtKB
- muscle organ development Source: UniProtKB-KW
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of mitotic cell cycle Source: UniProtKB
- protein deubiquitination Source: UniProtKB
- protein stabilization Source: UniProtKB
- ubiquitin-dependent protein catabolic process Source: InterPro
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Biological rhythms, Cell cycle, Myogenesis, Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | O75604 |
Reactomei | R-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
MEROPSi | C19.013 |
MoonDBi | O75604, 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000036672.15 |
HGNCi | HGNC:12618, USP2 |
MIMi | 604725, gene |
neXtProti | NX_O75604 |
Subcellular locationi
Other locations
- Cytoplasm By similarity
- 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
Nucleus
- Nucleus By similarity
Other locations
- Membrane By similarity; Peripheral membrane protein Curated
- Cytoplasm By similarity
Note: Predominantly expressed at membranes.By similarity
Cytoskeleton
- centrosome Source: Ensembl
Nucleus
- nucleoplasm Source: Reactome
Other locations
- cytoplasm Source: GO_Central
- membrane Source: UniProtKB-SubCell
- perinuclear region of cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, Membrane, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 276 | C → A: Loss of enzymatic activity. Increases the steady-state level of CCND1. 1 Publication | 1 | |
Mutagenesisi | 549 | H → 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 Publications | 1 |
Organism-specific databases
DisGeNETi | 9099 |
OpenTargetsi | ENSG00000036672 |
PharmGKBi | PA37244 |
Miscellaneous databases
Pharosi | O75604, Tbio |
Chemistry databases
ChEMBLi | CHEMBL1293227 |
Polymorphism and mutation databases
BioMutai | USP2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080616 | 1 – 605 | Ubiquitin carboxyl-terminal hydrolase 2Add BLAST | 605 |
Proteomic databases
MassIVEi | O75604 |
MaxQBi | O75604 |
PaxDbi | O75604 |
PeptideAtlasi | O75604 |
PRIDEi | O75604 |
ProteomicsDBi | 22761 50112 [O75604-1] 50113 [O75604-2] 50114 [O75604-3] 50115 [O75604-4] |
PTM databases
iPTMneti | O75604 |
PhosphoSitePlusi | O75604 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000036672, Expressed in hindlimb stylopod muscle and 198 other tissues |
ExpressionAtlasi | O75604, baseline and differential |
Genevisiblei | O75604, HS |
Organism-specific databases
HPAi | ENSG00000036672, Tissue enhanced (skeletal) |
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 PublicationsBinary interactionsi
O75604
GO - Molecular functioni
- cyclin binding Source: UniProtKB
- identical protein binding Source: Ensembl
- ubiquitin protein ligase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 114553, 199 interactors |
CORUMi | O75604 |
DIPi | DIP-29134N |
IntActi | O75604, 115 interactors |
MINTi | O75604 |
STRINGi | 9606.ENSP00000260187 |
Chemistry databases
BindingDBi | O75604 |
Miscellaneous databases
RNActi | O75604, protein |
Structurei
Secondary structure
3D structure databases
SMRi | O75604 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O75604 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 267 – 599 | USPAdd BLAST | 333 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 200 | Necessary for interaction with MDM41 PublicationAdd BLAST | 200 | |
Regioni | 403 – 503 | Necessary for interaction with MDM41 PublicationAdd BLAST | 101 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1868, Eukaryota |
GeneTreei | ENSGT00940000161289 |
HOGENOMi | CLU_008279_1_2_1 |
InParanoidi | O75604 |
OMAi | AFINLTN |
OrthoDBi | 1283205at2759 |
PhylomeDBi | O75604 |
TreeFami | TF106277 |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS00972, USP_1, 1 hit PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PJ34 | E9PJ34_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP2 | 137 | Annotation score: | ||
E9PSH6 | E9PSH6_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP2 | 167 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Sequence conflicti | 421 | S → G in BAB71388 (PubMed:14702039).Curated | 1 | ||
Sequence conflicti | 501 | H → R in BAB71388 (PubMed:14702039).Curated | 1 | ||
Sequence conflicti | 594 | L → H in AAC28392 (Ref. 1) Curated | 1 | ||
Sequence conflicti | 602 – 605 | PSRM → TSPI in AAC28392 (Ref. 1) Curated | 4 | ||
Isoform 3 (identifier: O75604-3) | |||||
Sequence conflicti | 10 | Y → S in AAH41366 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051519 | 174 | R → Q. Corresponds to variant dbSNP:rs33929148Ensembl. | 1 | |
Natural variantiVAR_051520 | 383 | N → S. Corresponds to variant dbSNP:rs45533837Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_039559 | 1 – 258 | MSQLS…GRDGM → MLVPGSTRPYSKKRQ in isoform 3. 1 PublicationAdd BLAST | 258 | |
Alternative sequenceiVSP_039560 | 1 – 258 | MSQLS…GRDGM → MRTSYTVTLPEDPPAAPFPA LAKELRPRSPLSPSLLLSTF VGLLLNKAK in isoform 4. 2 PublicationsAdd BLAST | 258 | |
Alternative sequenceiVSP_005256 | 1 – 252 | Missing in isoform 2. 1 PublicationAdd BLAST | 252 | |
Alternative sequenceiVSP_005257 | 253 – 258 | PGRDGM → MLNKAK in isoform 2. 1 Publication | 6 |
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 |
CCDSi | CCDS58189.1 [O75604-3] CCDS8422.1 [O75604-1] CCDS8423.1 [O75604-4] |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000260187; ENSP00000260187; ENSG00000036672 [O75604-1] ENST00000455332; ENSP00000407842; ENSG00000036672 [O75604-3] ENST00000525735; ENSP00000436952; ENSG00000036672 [O75604-4] |
GeneIDi | 9099 |
KEGGi | hsa:9099 |
UCSCi | uc001pwl.5, human [O75604-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar 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 |
CCDSi | CCDS58189.1 [O75604-3] CCDS8422.1 [O75604-1] CCDS8423.1 [O75604-4] |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2HD5 | X-ray | 1.85 | A | 258-605 | [»] | |
2IBI | X-ray | 2.20 | A | 251-605 | [»] | |
3NHE | X-ray | 1.26 | A | 258-605 | [»] | |
3V6C | X-ray | 1.70 | A | 258-605 | [»] | |
3V6E | X-ray | 2.10 | A | 258-605 | [»] | |
5XU8 | X-ray | 1.81 | A | 258-605 | [»] | |
5XVE | X-ray | 1.24 | A | 258-605 | [»] | |
6DGF | X-ray | 2.34 | A | 250-605 | [»] | |
SMRi | O75604 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114553, 199 interactors |
CORUMi | O75604 |
DIPi | DIP-29134N |
IntActi | O75604, 115 interactors |
MINTi | O75604 |
STRINGi | 9606.ENSP00000260187 |
Chemistry databases
BindingDBi | O75604 |
ChEMBLi | CHEMBL1293227 |
Protein family/group databases
MEROPSi | C19.013 |
MoonDBi | O75604, Predicted |
PTM databases
iPTMneti | O75604 |
PhosphoSitePlusi | O75604 |
Polymorphism and mutation databases
BioMutai | USP2 |
Proteomic databases
MassIVEi | O75604 |
MaxQBi | O75604 |
PaxDbi | O75604 |
PeptideAtlasi | O75604 |
PRIDEi | O75604 |
ProteomicsDBi | 22761 50112 [O75604-1] 50113 [O75604-2] 50114 [O75604-3] 50115 [O75604-4] |
Protocols and materials databases
Antibodypediai | 1707, 402 antibodies |
DNASUi | 9099 |
Genome annotation databases
Ensembli | ENST00000260187; ENSP00000260187; ENSG00000036672 [O75604-1] ENST00000455332; ENSP00000407842; ENSG00000036672 [O75604-3] ENST00000525735; ENSP00000436952; ENSG00000036672 [O75604-4] |
GeneIDi | 9099 |
KEGGi | hsa:9099 |
UCSCi | uc001pwl.5, human [O75604-1] |
Organism-specific databases
CTDi | 9099 |
DisGeNETi | 9099 |
EuPathDBi | HostDB:ENSG00000036672.15 |
GeneCardsi | USP2 |
HGNCi | HGNC:12618, USP2 |
HPAi | ENSG00000036672, Tissue enhanced (skeletal) |
MIMi | 604725, gene |
neXtProti | NX_O75604 |
OpenTargetsi | ENSG00000036672 |
PharmGKBi | PA37244 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1868, Eukaryota |
GeneTreei | ENSGT00940000161289 |
HOGENOMi | CLU_008279_1_2_1 |
InParanoidi | O75604 |
OMAi | AFINLTN |
OrthoDBi | 1283205at2759 |
PhylomeDBi | O75604 |
TreeFami | TF106277 |
Enzyme and pathway databases
PathwayCommonsi | O75604 |
Reactomei | R-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
BioGRID-ORCSi | 9099, 5 hits in 847 CRISPR screens |
ChiTaRSi | USP2, human |
EvolutionaryTracei | O75604 |
GeneWikii | USP2 |
GenomeRNAii | 9099 |
Pharosi | O75604, Tbio |
PROi | PR:O75604 |
RNActi | O75604, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000036672, Expressed in hindlimb stylopod muscle and 198 other tissues |
ExpressionAtlasi | O75604, baseline and differential |
Genevisiblei | O75604, HS |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS00972, USP_1, 1 hit PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | UBP2_HUMAN | |
Accessioni | O75604Primary (citable) accession number: O75604 Secondary accession number(s): B0YJB8 Q9BQ21 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | March 27, 2002 | |
Last modified: | December 2, 2020 | |
This is version 189 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Peptidase families
Classification of peptidase families and list of entries