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Protein

Ubiquitin carboxyl-terminal hydrolase 25

Gene

Usp25

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Deubiquitinating enzyme that hydrolyzes ubiquitin moieties conjugated to substrates and thus, functions to process newly synthesized Ubiquitin, to recycle ubiquitin molecules or to edit polyubiquitin chains and prevents proteasomal degradation of substrates. Hydrolyzes both 'Lys-48'- and 'Lys-63'-linked tetraubiquitin chains (By similarity).By similarity
The muscle-specific isoform (USP25m) may have a role in the regulation of muscular differentiation and function.

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).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei178NucleophilePROSITE-ProRule annotation1
Active sitei608Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-5689880. Ub-specific processing proteases.

Protein family/group databases

MEROPSiC19.041.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 25 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 25
Ubiquitin thioesterase 25
Ubiquitin-specific-processing protease 25
Short name:
mUSP25
Gene namesi
Name:Usp25
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1353655. Usp25.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • endoplasmic reticulum Source: MGI
  • nucleus Source: UniProtKB-SubCell
  • proteasome complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806541 – 1055Ubiquitin carboxyl-terminal hydrolase 25Add BLAST1055

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei85PhosphoserineBy similarity1
Cross-linki99Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki99Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei740PhosphotyrosineBy similarity1

Post-translational modificationi

Acetylated.By similarity
Sumoylation impairs binding to and hydrolysis of ubiquitin chains. Sumoylated preferentially with SUMO2 or SUMO3. Desumoylated by SENP1. Regulated by ubiquitination on the same residue (By similarity).By similarity
Preferentially monoubiquitinated but can also be polyubiquitinated. Autodeubiquitinated. Ubiquitination activates the enzymatic activity either by preventing sumoylation or by allowing novel interactions (By similarity).By similarity
Phosphorylation in the C-terminal by SYK regulates USP25 cellular levels.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP57080.
MaxQBiP57080.
PaxDbiP57080.
PeptideAtlasiP57080.
PRIDEiP57080.

PTM databases

iPTMnetiP57080.
PhosphoSitePlusiP57080.

Expressioni

Tissue specificityi

Highly expressed in testis especially in primary and secondary spematocytes and in immature spermatids. Also found in brain, skeletal muscle, liver and heart.1 Publication

Developmental stagei

At E13.5 and E16.5, expression in the brain correlates with the proliferate ventricular zone and post-mitotic neurons of the intermediate zone, particularly in the forebrain. More marked expression at E16.5 in the telencephalic septum and in the pallium. In myocytes, expressed throughout differentiation of myotubes.2 Publications

Gene expression databases

BgeeiENSMUSG00000022867.
CleanExiMM_USP25.
GenevisibleiP57080. MM.

Interactioni

Subunit structurei

Homodimer or oligomer (By similarity). 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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi206017. 1 interactor.
IntActiP57080. 2 interactors.
STRINGi10090.ENSMUSP00000023580.

Structurei

Secondary structure

11055
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 12Combined sources4
Helixi17 – 27Combined sources11
Helixi33 – 43Combined sources11
Helixi47 – 55Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1VDLNMR-A1-67[»]
ProteinModelPortaliP57080.
SMRiP57080.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP57080.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 57UBA-likeAdd BLAST44
Domaini97 – 116UIM 1PROSITE-ProRule annotationAdd BLAST20
Domaini123 – 140UIM 2PROSITE-ProRule annotationAdd BLAST18
Domaini169 – 658USPAdd BLAST490

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni77 – 102SUMO interaction domain (SIM)Add BLAST26

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi89 – 95Required for SUMO paralog-specific binding7

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated
Contains 1 UBA-like domain.Curated
Contains 2 UIM (ubiquitin-interacting motif) domains.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG1863. Eukaryota.
COG5077. LUCA.
GeneTreeiENSGT00390000016082.
HOGENOMiHOG000007956.
HOVERGENiHBG056030.
InParanoidiP57080.
KOiK11849.
OMAiNMQGIIM.
OrthoDBiEOG091G00QR.
PhylomeDBiP57080.
TreeFamiTF329035.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR009060. UBA-like.
IPR003903. UIM_dom.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
PF02809. UIM. 2 hits.
[Graphical view]
SMARTiSM00726. UIM. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
PROSITEiPS50330. UIM. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

This entry describes 1 isoform i produced by alternative splicing. AlignAdd to basket

Note: A longer muscle-specific isoform, USP25m, also exists.
Isoform 1 (identifier: P57080-1) [UniParc]FASTAAdd to basket

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
MTVEQNVLQQ SAAQKHQQTF LNQLREITGI NDAQILQQAL KDSNGNLELA
60 70 80 90 100
VAFLTAKNAK TPPQEETGYY QTALPGNDRY ISVGSQADAN VIDLTGDDKD
110 120 130 140 150
DLQRAIALSL AESNRAFRET GITDEEQAIS RVLEASIAEN KACLKRTPIE
160 170 180 190 200
VWRDSRNPYD RKRQEKAPVG 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
GRFLAMGVLE GKKFENTEMF GQYPLQVNGF KDLHECLEAA MIEGEIESLH
360 370 380 390 400
SDNSGKSGQE HWFTELPPVL TFELSRFEFN QALGRPEKIH NKLEFPQVLY
410 420 430 440 450
LDRYMHRNRE ITRIKREEIK RLKDYLTVLQ QRLERYLSYG SGPKRFPLVD
460 470 480 490 500
VLQYALEFAS SKPVCTSPVD DIDASSSASG PLPSQSLPST TEQQGPCASD
510 520 530 540 550
LPGSSSPASG AALPLRSVIH KPFTQSRIPP DLPMHPAPRH ITEEELCVLE
560 570 580 590 600
SCLHRWRTEI ENDTRDLQES ISRIHRTIEL MYSDKSMIQV PYRLHAVLVH
610 620 630 640 650
EGQANAGHYW AYIFDHRESR WMKYNDIAVT KSSWEELVRD SFGGYRNASA
660 670 680 690 700
YCLMYIDDKA QFLIQEEFNK ETGQALVGME TLPPDLRDFV EEDNQRFEKE
710 720 730 740 750
LEEWDTQLAQ RSLQEKLLAA PKLREAEASA TTAQAGGADY LEQPSRSDLS
760 770 780 790 800
KHWKEETLRV IAKASHDLED KGPETVLQSA IKLEYSRLVK LAQEDTPPET
810 820 830 840 850
DYRLHHVLVY FIQNQAPKKI IEKTLLEQFG DRNLSFDERC HNIMKVAQAK
860 870 880 890 900
LEMIKPEEVN LEEYEEWHAD YKKFRETTMY LITGLENFQR ESYIDSLLFL
910 920 930 940 950
LCAYQNNKEL LSKGPYRGHD GELISHYRRE CLLKLNEQAA ELFESGEDGD
960 970 980 990 1000
VNNGLIIMNE FIVPFLPLLL VDDMEEKDIL AVEDMRNRWC SYLGQEMEAN
1010 1020 1030 1040 1050
LQEKLTDFLP KLLDCSTEIK GFHEPPKLPS YSAHELCERF ARIMLSLSRT

PADGR
Length:1,055
Mass (Da):121,420
Last modified:April 13, 2004 - v2
Checksum:i103E34EC3FA8A72B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti394E → K in AAF32264 (PubMed:10644437).Curated1
Sequence conflicti496P → L in AAF32264 (PubMed:10644437).Curated1
Sequence conflicti683P → L in AAF32264 (PubMed:10644437).Curated1
Sequence conflicti841H → L in AAF32264 (PubMed:10644437).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF170563 mRNA. Translation: AAF32264.1.
BC048171 mRNA. Translation: AAH48171.1.
BC063059 mRNA. Translation: AAH63059.1.
CCDSiCCDS28275.1. [P57080-1]
RefSeqiNP_038946.2. NM_013918.2. [P57080-1]
UniGeneiMm.40986.

Genome annotation databases

EnsembliENSMUST00000023580; ENSMUSP00000023580; ENSMUSG00000022867. [P57080-1]
GeneIDi30940.
KEGGimmu:30940.
UCSCiuc007zsb.1. mouse. [P57080-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF170563 mRNA. Translation: AAF32264.1.
BC048171 mRNA. Translation: AAH48171.1.
BC063059 mRNA. Translation: AAH63059.1.
CCDSiCCDS28275.1. [P57080-1]
RefSeqiNP_038946.2. NM_013918.2. [P57080-1]
UniGeneiMm.40986.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1VDLNMR-A1-67[»]
ProteinModelPortaliP57080.
SMRiP57080.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi206017. 1 interactor.
IntActiP57080. 2 interactors.
STRINGi10090.ENSMUSP00000023580.

Protein family/group databases

MEROPSiC19.041.

PTM databases

iPTMnetiP57080.
PhosphoSitePlusiP57080.

Proteomic databases

EPDiP57080.
MaxQBiP57080.
PaxDbiP57080.
PeptideAtlasiP57080.
PRIDEiP57080.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000023580; ENSMUSP00000023580; ENSMUSG00000022867. [P57080-1]
GeneIDi30940.
KEGGimmu:30940.
UCSCiuc007zsb.1. mouse. [P57080-1]

Organism-specific databases

CTDi29761.
MGIiMGI:1353655. Usp25.

Phylogenomic databases

eggNOGiKOG1863. Eukaryota.
COG5077. LUCA.
GeneTreeiENSGT00390000016082.
HOGENOMiHOG000007956.
HOVERGENiHBG056030.
InParanoidiP57080.
KOiK11849.
OMAiNMQGIIM.
OrthoDBiEOG091G00QR.
PhylomeDBiP57080.
TreeFamiTF329035.

Enzyme and pathway databases

ReactomeiR-MMU-5689880. Ub-specific processing proteases.

Miscellaneous databases

ChiTaRSiUsp25. mouse.
EvolutionaryTraceiP57080.
PROiP57080.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022867.
CleanExiMM_USP25.
GenevisibleiP57080. MM.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR009060. UBA-like.
IPR003903. UIM_dom.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
PF02809. UIM. 2 hits.
[Graphical view]
SMARTiSM00726. UIM. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
PROSITEiPS50330. UIM. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP25_MOUSE
AccessioniPrimary (citable) accession number: P57080
Secondary accession number(s): Q80ZT9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: April 13, 2004
Last modified: November 30, 2016
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.