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P57080

- UBP25_MOUSE

UniProt

P57080 - UBP25_MOUSE

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Protein

Ubiquitin carboxyl-terminal hydrolase 25

Gene

Usp25

Organism
Mus musculus (Mouse)
Status
Reviewed - 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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei178 – 1781NucleophilePROSITE-ProRule annotation
Active sitei608 – 6081Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

  1. ubiquitin-specific protease activity Source: MGI

GO - Biological processi

  1. protein K48-linked deubiquitination Source: Ensembl
  2. protein K63-linked deubiquitination Source: Ensembl
  3. ubiquitin-dependent protein catabolic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

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
ProteomesiUP000000589: Chromosome 16

Organism-specific databases

MGIiMGI:1353655. Usp25.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus 1 Publication
Note: The longer muscle-specific isoform (USP25m) Some transient punctuate nuclear location in myotubes during myocyte development.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. nucleus Source: UniProtKB-KW
  3. proteasome complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10551055Ubiquitin carboxyl-terminal hydrolase 25PRO_0000080654Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki99 – 99Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki99 – 99Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei740 – 7401PhosphotyrosineBy similarity

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

MaxQBiP57080.
PaxDbiP57080.
PRIDEiP57080.

PTM databases

PhosphoSiteiP57080.

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

BgeeiP57080.
CleanExiMM_USP25.
ExpressionAtlasiP57080. baseline and differential.
GenevestigatoriP57080.

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

Protein-protein interaction databases

IntActiP57080. 2 interactions.

Structurei

Secondary structure

1
1055
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi9 – 124Combined sources
Helixi17 – 2711Combined sources
Helixi33 – 4311Combined sources
Helixi47 – 559Combined sources

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1VDLNMR-A1-67[»]
ProteinModelPortaliP57080.
SMRiP57080. Positions 1-138, 169-407, 592-677.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP57080.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 5744UBA-likeAdd
BLAST
Repeati97 – 11620UIM 1Add
BLAST
Repeati123 – 14018UIM 2Add
BLAST
Domaini169 – 658490USPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni77 – 10226SUMO interaction domain (SIM)Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi89 – 957Required for SUMO paralog-specific binding

Sequence similaritiesi

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

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiCOG5077.
GeneTreeiENSGT00390000016082.
HOGENOMiHOG000007956.
HOVERGENiHBG056030.
InParanoidiP57080.
KOiK11849.
OMAiSRSVIHK.
OrthoDBiEOG761BSZ.
PhylomeDBiP57080.
TreeFamiTF329035.

Family and domain databases

InterProiIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR009060. UBA-like.
IPR003903. Ubiquitin-int_motif.
IPR028889. UCH/PAN2.
[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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti394 – 3941E → K in AAF32264. (PubMed:10644437)Curated
Sequence conflicti496 – 4961P → L in AAF32264. (PubMed:10644437)Curated
Sequence conflicti683 – 6831P → L in AAF32264. (PubMed:10644437)Curated
Sequence conflicti841 – 8411H → L in AAF32264. (PubMed:10644437)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
AF170563 mRNA. Translation: AAF32264.1 .
BC048171 mRNA. Translation: AAH48171.1 .
BC063059 mRNA. Translation: AAH63059.1 .
CCDSi CCDS28275.1. [P57080-1 ]
RefSeqi NP_038946.2. NM_013918.2. [P57080-1 ]
UniGenei Mm.40986.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1VDL NMR - A 1-67 [» ]
ProteinModelPortali P57080.
SMRi P57080. Positions 1-138, 169-407, 592-677.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P57080. 2 interactions.

Protein family/group databases

MEROPSi C19.041.

PTM databases

PhosphoSitei P57080.

Proteomic databases

MaxQBi P57080.
PaxDbi P57080.
PRIDEi P57080.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000023580 ; ENSMUSP00000023580 ; ENSMUSG00000022867 . [P57080-1 ]
GeneIDi 30940.
KEGGi mmu:30940.
UCSCi uc007zsb.1. mouse. [P57080-1 ]

Organism-specific databases

CTDi 29761.
MGIi MGI:1353655. Usp25.

Phylogenomic databases

eggNOGi COG5077.
GeneTreei ENSGT00390000016082.
HOGENOMi HOG000007956.
HOVERGENi HBG056030.
InParanoidi P57080.
KOi K11849.
OMAi SRSVIHK.
OrthoDBi EOG761BSZ.
PhylomeDBi P57080.
TreeFami TF329035.

Miscellaneous databases

ChiTaRSi USP25. mouse.
EvolutionaryTracei P57080.
NextBioi 307378.
PROi P57080.
SOURCEi Search...

Gene expression databases

Bgeei P57080.
CleanExi MM_USP25.
ExpressionAtlasi P57080. baseline and differential.
Genevestigatori P57080.

Family and domain databases

InterProi IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR009060. UBA-like.
IPR003903. Ubiquitin-int_motif.
IPR028889. UCH/PAN2.
[Graphical view ]
Pfami PF00443. UCH. 1 hit.
PF02809. UIM. 2 hits.
[Graphical view ]
SMARTi SM00726. UIM. 1 hit.
[Graphical view ]
SUPFAMi SSF46934. SSF46934. 1 hit.
PROSITEi PS50330. UIM. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "USP25, a novel gene encoding a deubiquitinating enzyme, is located in the gene-poor region 21q11.2."
    Valero R., Marfany G., Gonzalez-Angulo O., Gonzalez-Gonzalez G., Puelles L., Gonzalez-Duarte R.
    Genomics 62:395-405(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
    Tissue: Kidney.
  2. "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].
    Strain: C57BL/6.
    Tissue: Brain.
  3. "Solution structure of RSGI RUH-013, a UBA domain in mouse."
    RIKEN structural genomics initiative (RSGI)
    Submitted (SEP-2004) to the PDB data bank
    Cited for: STRUCTURE BY NMR OF 1-67.
  4. "The ubiquitin-specific protease USP25 interacts with three sarcomeric proteins."
    Bosch-Comas A., Lindsten K., Gonzalez-Duarte R., Masucci M.G., Marfany G.
    Cell. Mol. Life Sci. 63:723-734(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING, DEVELOPMENTAL STAGE, POSSIBLE FUNCTION, SUBCELLULAR LOCATION.

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: October 29, 2014
This is version 117 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

External Data

Dasty 3