UniProtKB - Q9UHP3 (UBP25_HUMAN)
Ubiquitin carboxyl-terminal hydrolase 25
USP25
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
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 178 | 1 Publication | 1 | |
Active sitei | 599 | By similarity | 1 | |
Active sitei | 607 | By similarity | 1 |
GO - Molecular functioni
- ATPase binding Source: ParkinsonsUK-UCL
- cysteine-type endopeptidase activity Source: GO_Central
- peptidase activity Source: ProtInc
- SUMO binding Source: UniProtKB
- thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
- ubiquitin binding Source: ParkinsonsUK-UCL
- ubiquitin-like protein-specific protease activity Source: ParkinsonsUK-UCL
- ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
GO - Biological processi
- cellular protein modification process Source: ProtInc
- negative regulation of ERAD pathway Source: ParkinsonsUK-UCL
- protein deubiquitination Source: ParkinsonsUK-UCL
- protein K48-linked deubiquitination Source: UniProtKB
- protein K63-linked deubiquitination Source: UniProtKB
- proteolysis Source: ProtInc
- ubiquitin-dependent protein catabolic process Source: InterPro
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Ubl conjugation pathway |
Enzyme and pathway databases
PathwayCommonsi | Q9UHP3 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases |
Protein family/group databases
MEROPSi | C19.041 |
Names & Taxonomyi
Protein namesi | Recommended name: Ubiquitin carboxyl-terminal hydrolase 25 (EC:3.4.19.12)Alternative name(s): Deubiquitinating enzyme 25 USP on chromosome 21 Ubiquitin thioesterase 25 Ubiquitin-specific-processing protease 25 |
Gene namesi | Name:USP25 Synonyms:USP21 |
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
HGNCi | HGNC:12624, USP25 |
MIMi | 604736, gene |
neXtProti | NX_Q9UHP3 |
VEuPathDBi | HostDB:ENSG00000155313.15 |
Subcellular locationi
Other locations
- Cytoplasm 2 Publications
Cytosol
- cytosol Source: HPA
Endoplasmic reticulum
- endoplasmic reticulum Source: ParkinsonsUK-UCL
Nucleus
- nucleus Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 91 | V → A: No interaction with SUMO3; when associated with A-92. 1 Publication | 1 | |
Mutagenesisi | 92 | I → A: No interaction with SUMO3; when associated with A-91. 1 Publication | 1 | |
Mutagenesisi | 99 | K → R: Abolishes sumoylation. Decreased enzymatic activity. 2 Publications | 1 | |
Mutagenesisi | 178 | C → S: Abrogates deubiquitinating activity. No effect on homo- or oligomerization. 1 Publication | 1 | |
Mutagenesisi | 740 | Y → F: No effect on interaction with SYK. 1 Publication | 1 | |
Mutagenesisi | 878 | T → I: No effect on interaction with SYK. 1 Publication | 1 | |
Mutagenesisi | 880 | Y → F: No effect on interaction with SYK. 1 Publication | 1 | |
Mutagenesisi | 883 | I → S: No effect on interaction with SYK. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 29761 |
OpenTargetsi | ENSG00000155313 |
PharmGKBi | PA37249 |
Miscellaneous databases
Pharosi | Q9UHP3, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4295975 |
Genetic variation databases
BioMutai | USP25 |
DMDMi | 302393833 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080653 | 1 – 1055 | Ubiquitin carboxyl-terminal hydrolase 25Add BLAST | 1055 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 85 | PhosphoserineCombined sources | 1 | |
Cross-linki | 99 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||
Cross-linki | 99 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication | ||
Modified residuei | 740 | Phosphotyrosine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q9UHP3 |
jPOSTi | Q9UHP3 |
MassIVEi | Q9UHP3 |
MaxQBi | Q9UHP3 |
PaxDbi | Q9UHP3 |
PeptideAtlasi | Q9UHP3 |
PRIDEi | Q9UHP3 |
ProteomicsDBi | 84385 [Q9UHP3-2] 84386 [Q9UHP3-1] 84387 [Q9UHP3-3] |
PTM databases
iPTMneti | Q9UHP3 |
PhosphoSitePlusi | Q9UHP3 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000155313, Expressed in sperm and 239 other tissues |
ExpressionAtlasi | Q9UHP3, baseline and differential |
Genevisiblei | Q9UHP3, HS |
Organism-specific databases
HPAi | ENSG00000155313, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer or oligomer.
Interacts with ACTA1 (via its C-terminus); the interaction occurs for all isoforms but is strongest for isoform USP25m in muscle differentiating cells.
Interacts (isoform USP25m only) with MYBPC1; the interaction prevents proteasomal degradation of MYBPC1.
Interacts (isoform USP25m only) with FLNC (via filament repeats 17-18, 20-21 and 24).
Interacts with GAPDH.
Interacts with SUMO3; the interaction sumoylates efficiently USP25.
Interacts with SUMO2; the interaction sumoylates efficiently USP25.
Interacts with SUMO1; the interaction only weakly sumoylates USP25.
Interacts with SYK; phosphorylates USP25 and regulates USP25 intracellular levels.
4 PublicationsBinary interactionsi
Hide detailsQ9UHP3
GO - Molecular functioni
- ATPase binding Source: ParkinsonsUK-UCL
- SUMO binding Source: UniProtKB
- ubiquitin binding Source: ParkinsonsUK-UCL
- ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
Protein-protein interaction databases
BioGRIDi | 118895, 75 interactors |
IntActi | Q9UHP3, 38 interactors |
MINTi | Q9UHP3 |
STRINGi | 9606.ENSP00000383044 |
Chemistry databases
BindingDBi | Q9UHP3 |
Miscellaneous databases
RNActi | Q9UHP3, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | Q9UHP3 |
SMRi | Q9UHP3 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 14 – 57 | UBA-likeAdd BLAST | 44 | |
Domaini | 97 – 116 | UIM 1PROSITE-ProRule annotationAdd BLAST | 20 | |
Domaini | 123 – 140 | UIM 2PROSITE-ProRule annotationAdd BLAST | 18 | |
Domaini | 169 – 657 | USPAdd BLAST | 489 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 77 – 102 | SUMO interaction domain (SIM)Add BLAST | 26 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 541 – 578 | Sequence analysisAdd BLAST | 38 | |
Coiled coili | 684 – 717 | Sequence analysisAdd BLAST | 34 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 89 – 95 | Required for SUMO paralog-specific binding | 7 |
Sequence similaritiesi
Keywords - Domaini
Coiled coil, RepeatPhylogenomic databases
eggNOGi | KOG1863, Eukaryota |
GeneTreei | ENSGT00940000157962 |
HOGENOMi | CLU_012188_0_0_1 |
InParanoidi | Q9UHP3 |
OMAi | XAIKLEY |
OrthoDBi | 194025at2759 |
PhylomeDBi | Q9UHP3 |
TreeFami | TF329035 |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR009060, UBA-like_sf IPR003903, UIM_dom IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit PF02809, UIM, 2 hits |
SMARTi | View protein in SMART SM00726, UIM, 1 hit |
SUPFAMi | SSF46934, SSF46934, 1 hit SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS50330, UIM, 1 hit PS00972, USP_1, 1 hit PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 3 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
MTVEQNVLQQ SAAQKHQQTF LNQLREITGI NDTQILQQAL KDSNGNLELA
60 70 80 90 100
VAFLTAKNAK TPQQEETTYY QTALPGNDRY ISVGSQADTN VIDLTGDDKD
110 120 130 140 150
DLQRAIALSL AESNRAFRET GITDEEQAIS RVLEASIAEN KACLKRTPTE
160 170 180 190 200
VWRDSRNPYD RKRQDKAPVG LKNVGNTCWF SAVIQSLFNL LEFRRLVLNY
210 220 230 240 250
KPPSNAQDLP RNQKEHRNLP FMRELRYLFA LLVGTKRKYV DPSRAVEILK
260 270 280 290 300
DAFKSNDSQQ QDVSEFTHKL LDWLEDAFQM KAEEETDEEK PKNPMVELFY
310 320 330 340 350
GRFLAVGVLE GKKFENTEMF GQYPLQVNGF KDLHECLEAA MIEGEIESLH
360 370 380 390 400
SENSGKSGQE HWFTELPPVL TFELSRFEFN QALGRPEKIH NKLEFPQVLY
410 420 430 440 450
LDRYMHRNRE ITRIKREEIK RLKDYLTVLQ QRLERYLSYG SGPKRFPLVD
460 470 480 490 500
VLQYALEFAS SKPVCTSPVD DIDASSPPSG SIPSQTLPST TEQQGALSSE
510 520 530 540 550
LPSTSPSSVA AISSRSVIHK PFTQSRIPPD LPMHPAPRHI TEEELSVLES
560 570 580 590 600
CLHRWRTEIE NDTRDLQESI SRIHRTIELM YSDKSMIQVP YRLHAVLVHE
610 620 630 640 650
GQANAGHYWA YIFDHRESRW MKYNDIAVTK SSWEELVRDS FGGYRNASAY
660 670 680 690 700
CLMYINDKAQ FLIQEEFNKE TGQPLVGIET LPPDLRDFVE EDNQRFEKEL
710 720 730 740 750
EEWDAQLAQK ALQEKLLASQ KLRESETSVT TAQAAGDPEY LEQPSRSDFS
760 770 780 790 800
KHLKEETIQI ITKASHEHED KSPETVLQSA IKLEYARLVK LAQEDTPPET
810 820 830 840 850
DYRLHHVVVY FIQNQAPKKI IEKTLLEQFG DRNLSFDERC HNIMKVAQAK
860 870 880 890 900
LEMIKPEEVN LEEYEEWHQD YRKFRETTMY LIIGLENFQR ESYIDSLLFL
910 920 930 940 950
ICAYQNNKEL LSKGLYRGHD EELISHYRRE CLLKLNEQAA ELFESGEDRE
960 970 980 990 1000
VNNGLIIMNE FIVPFLPLLL VDEMEEKDIL AVEDMRNRWC SYLGQEMEPH
1010 1020 1030 1040 1050
LQEKLTDFLP KLLDCSMEIK SFHEPPKLPS YSTHELCERF ARIMLSLSRT
PADGR
The sequence of this isoform differs from the canonical sequence as follows:
779-779: S → SIMMTPNMQGIIMAIGKSRSVYDRCGPEAGFFK
The sequence of this isoform differs from the canonical sequence as follows:
779-779: S → SKPENTTSQPLSNQRVVEVAIPHVGKFMIESKEGGYDDEIMMTPNMQGIIMAIGKSRSVYDRCGPEAGFFK
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ96B65 | Q96B65_HUMAN | USP25 protein | USP25 | 450 | Annotation score: | ||
H7C253 | H7C253_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP25 | 204 | Annotation score: | ||
H7C1T8 | H7C1T8_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP25 | 229 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 544 | E → K in AAF32263 (PubMed:10644437).Curated | 1 | |
Sequence conflicti | 544 | E → K in ACN76567 (Ref. 3) Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_039632 | 779 | S → SIMMTPNMQGIIMAIGKSRS VYDRCGPEAGFFK in isoform USP25b. 1 Publication | 1 | |
Alternative sequenceiVSP_039631 | 779 | S → SKPENTTSQPLSNQRVVEVA IPHVGKFMIESKEGGYDDEI MMTPNMQGIIMAIGKSRSVY DRCGPEAGFFK in isoform USP25m. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF170562 mRNA Translation: AAF32263.1 AF134213 mRNA Translation: AAF24998.1 FJ763652 mRNA Translation: ACN76567.1 CH471079 Genomic DNA Translation: EAX10041.1 BC075792 mRNA Translation: AAH75792.1 AK022574 mRNA Translation: BAB14107.1 |
CCDSi | CCDS33515.1 [Q9UHP3-2] CCDS63336.1 [Q9UHP3-3] CCDS63337.1 [Q9UHP3-1] |
RefSeqi | NP_001269970.1, NM_001283041.1 [Q9UHP3-3] NP_001269971.1, NM_001283042.1 [Q9UHP3-1] NP_037528.3, NM_013396.4 [Q9UHP3-2] |
Genome annotation databases
Ensembli | ENST00000285679; ENSP00000285679; ENSG00000155313 [Q9UHP3-2] ENST00000285681; ENSP00000285681; ENSG00000155313 [Q9UHP3-1] ENST00000400183; ENSP00000383044; ENSG00000155313 [Q9UHP3-3] |
GeneIDi | 29761 |
KEGGi | hsa:29761 |
UCSCi | uc002yjy.3, human [Q9UHP3-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF170562 mRNA Translation: AAF32263.1 AF134213 mRNA Translation: AAF24998.1 FJ763652 mRNA Translation: ACN76567.1 CH471079 Genomic DNA Translation: EAX10041.1 BC075792 mRNA Translation: AAH75792.1 AK022574 mRNA Translation: BAB14107.1 |
CCDSi | CCDS33515.1 [Q9UHP3-2] CCDS63336.1 [Q9UHP3-3] CCDS63337.1 [Q9UHP3-1] |
RefSeqi | NP_001269970.1, NM_001283041.1 [Q9UHP3-3] NP_001269971.1, NM_001283042.1 [Q9UHP3-1] NP_037528.3, NM_013396.4 [Q9UHP3-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2MUX | NMR | - | A | 1-146 | [»] | |
5GP7 | X-ray | 1.50 | B | 1046-1055 | [»] | |
5O71 | X-ray | 3.28 | A | 1-714 | [»] | |
6H4J | X-ray | 3.07 | A/B | 157-706 | [»] | |
6H4K | X-ray | 2.05 | A | 765-1055 | [»] | |
6HEL | X-ray | 2.94 | A/B | 157-714 | [»] | |
6HEM | X-ray | 1.72 | A | 748-1048 | [»] | |
BMRBi | Q9UHP3 | |||||
SMRi | Q9UHP3 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 118895, 75 interactors |
IntActi | Q9UHP3, 38 interactors |
MINTi | Q9UHP3 |
STRINGi | 9606.ENSP00000383044 |
Chemistry databases
BindingDBi | Q9UHP3 |
ChEMBLi | CHEMBL4295975 |
Protein family/group databases
MEROPSi | C19.041 |
PTM databases
iPTMneti | Q9UHP3 |
PhosphoSitePlusi | Q9UHP3 |
Genetic variation databases
BioMutai | USP25 |
DMDMi | 302393833 |
Proteomic databases
EPDi | Q9UHP3 |
jPOSTi | Q9UHP3 |
MassIVEi | Q9UHP3 |
MaxQBi | Q9UHP3 |
PaxDbi | Q9UHP3 |
PeptideAtlasi | Q9UHP3 |
PRIDEi | Q9UHP3 |
ProteomicsDBi | 84385 [Q9UHP3-2] 84386 [Q9UHP3-1] 84387 [Q9UHP3-3] |
Protocols and materials databases
Antibodypediai | 5805, 238 antibodies |
DNASUi | 29761 |
Genome annotation databases
Ensembli | ENST00000285679; ENSP00000285679; ENSG00000155313 [Q9UHP3-2] ENST00000285681; ENSP00000285681; ENSG00000155313 [Q9UHP3-1] ENST00000400183; ENSP00000383044; ENSG00000155313 [Q9UHP3-3] |
GeneIDi | 29761 |
KEGGi | hsa:29761 |
UCSCi | uc002yjy.3, human [Q9UHP3-2] |
Organism-specific databases
CTDi | 29761 |
DisGeNETi | 29761 |
GeneCardsi | USP25 |
HGNCi | HGNC:12624, USP25 |
HPAi | ENSG00000155313, Low tissue specificity |
MIMi | 604736, gene |
neXtProti | NX_Q9UHP3 |
OpenTargetsi | ENSG00000155313 |
PharmGKBi | PA37249 |
VEuPathDBi | HostDB:ENSG00000155313.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1863, Eukaryota |
GeneTreei | ENSGT00940000157962 |
HOGENOMi | CLU_012188_0_0_1 |
InParanoidi | Q9UHP3 |
OMAi | XAIKLEY |
OrthoDBi | 194025at2759 |
PhylomeDBi | Q9UHP3 |
TreeFami | TF329035 |
Enzyme and pathway databases
PathwayCommonsi | Q9UHP3 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases |
Miscellaneous databases
BioGRID-ORCSi | 29761, 3 hits in 880 CRISPR screens |
ChiTaRSi | USP25, human |
GenomeRNAii | 29761 |
Pharosi | Q9UHP3, Tbio |
PROi | PR:Q9UHP3 |
RNActi | Q9UHP3, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000155313, Expressed in sperm and 239 other tissues |
ExpressionAtlasi | Q9UHP3, baseline and differential |
Genevisiblei | Q9UHP3, HS |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR009060, UBA-like_sf IPR003903, UIM_dom IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit PF02809, UIM, 2 hits |
SMARTi | View protein in SMART SM00726, UIM, 1 hit |
SUPFAMi | SSF46934, SSF46934, 1 hit SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS50330, UIM, 1 hit PS00972, USP_1, 1 hit PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | UBP25_HUMAN | |
Accessioni | Q9UHP3Primary (citable) accession number: Q9UHP3 Secondary accession number(s): C0LSZ0, Q6DHZ9, Q9H9W1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | August 10, 2010 | |
Last modified: | February 10, 2021 | |
This is version 194 of the entry and version 4 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
- 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 21
Human chromosome 21: entries, gene names and cross-references to MIM - Peptidase families
Classification of peptidase families and list of entries