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Protein

Ubiquitin carboxyl-terminal hydrolase 25

Gene

USP25

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.
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 sitei1781 Publication1
Active sitei599By similarity1
Active sitei607By similarity1

GO - Molecular functioni

  • ATPase binding Source: ParkinsonsUK-UCL
  • peptidase activity Source: ProtInc
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitinyl hydrolase activity Source: Reactome
  • ubiquitin binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • ubiquitin-specific protease activity involved in negative regulation of ERAD pathway Source: ParkinsonsUK-UCL

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-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
USP on chromosome 21
Ubiquitin thioesterase 25
Ubiquitin-specific-processing protease 25
Gene namesi
Name:USP25
Synonyms:USP21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000155313.15
HGNCiHGNC:12624 USP25
MIMi604736 gene
neXtProtiNX_Q9UHP3

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, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91V → A: No interaction with SUMO3; when associated with A-92. 1 Publication1
Mutagenesisi92I → A: No interaction with SUMO3; when associated with A-91. 1 Publication1
Mutagenesisi99K → R: Abolishes sumoylation. Decreased enzymatic activity. 2 Publications1
Mutagenesisi178C → S: Abrogates deubiquitinating activity. No effect on homo- or oligomerization. 1 Publication1
Mutagenesisi740Y → F: No effect on interaction with SYK. 1 Publication1
Mutagenesisi878T → I: No effect on interaction with SYK. 1 Publication1
Mutagenesisi880Y → F: No effect on interaction with SYK. 1 Publication1
Mutagenesisi883I → S: No effect on interaction with SYK. 1 Publication1

Organism-specific databases

DisGeNETi29761
OpenTargetsiENSG00000155313
PharmGKBiPA37249

Polymorphism and mutation databases

DMDMi302393833

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806531 – 1055Ubiquitin carboxyl-terminal hydrolase 25Add BLAST1055

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei85PhosphoserineCombined sources1
Cross-linki99Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki99Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate1 Publication
Modified residuei740Phosphotyrosine1 Publication1

Post-translational modificationi

Acetylated.1 Publication
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.1 Publication
Preferentially monoubiquitinated but can also be polyubiquitinated. Autodeubiquitinated. Ubiquitination activates the enzymatic activity either by preventing sumoylation or by allowing novel interactions.1 Publication
Phosphorylation in the C-terminal by SYK regulates USP25 cellular levels.2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UHP3
MaxQBiQ9UHP3
PaxDbiQ9UHP3
PeptideAtlasiQ9UHP3
PRIDEiQ9UHP3
ProteomicsDBi84385
84386 [Q9UHP3-1]
84387 [Q9UHP3-3]

PTM databases

iPTMnetiQ9UHP3
PhosphoSitePlusiQ9UHP3

Expressioni

Tissue specificityi

Isoform USP25a is found in most adult and fetal tissues; expression is moderately high in testis, pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, but very low in peripheral blood, colon, small intestine, ovary, prostate, thymus and spleen. Isoform USP25b is found in all tissues except heart and skeletal muscle. Isoform USP25m is heart and skeletal muscle specific.2 Publications

Inductioni

The muscle-specific isoform (USP25m) is up-regulated during myocyte differentiation. Levels increase up to 100-fold towards completion of differentiation.1 Publication

Gene expression databases

BgeeiENSG00000155313 Expressed in 225 organ(s), highest expression level in sperm
CleanExiHS_USP21
HS_USP25
ExpressionAtlasiQ9UHP3 baseline and differential
GenevisibleiQ9UHP3 HS

Organism-specific databases

HPAiHPA018297
HPA024142

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 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118895, 53 interactors
IntActiQ9UHP3, 26 interactors
MINTiQ9UHP3
STRINGi9606.ENSP00000285679

Structurei

Secondary structure

11055
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UHP3
SMRiQ9UHP3
ModBaseiSearch...
MobiDBiSearch...

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 – 657USPAdd BLAST489

Region

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

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili541 – 578Sequence analysisAdd BLAST38
Coiled coili684 – 717Sequence analysisAdd BLAST34

Motif

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

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG1863 Eukaryota
COG5077 LUCA
GeneTreeiENSGT00390000016082
HOGENOMiHOG000007956
HOVERGENiHBG056030
InParanoidiQ9UHP3
KOiK11849
OMAiWAYIFDH
OrthoDBiEOG091G00QR
PhylomeDBiQ9UHP3
TreeFamiTF329035

Family and domain databases

InterProiView 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
PfamiView protein in Pfam
PF00443 UCH, 1 hit
PF02809 UIM, 2 hits
SMARTiView protein in SMART
SM00726 UIM, 1 hit
SUPFAMiSSF46934 SSF46934, 1 hit
SSF54001 SSF54001, 2 hits
PROSITEiView protein in PROSITE
PS50330 UIM, 1 hit
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform USP25a (identifier: Q9UHP3-2) [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 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
Length:1,055
Mass (Da):122,218
Last modified:August 10, 2010 - v4
Checksum:i0B9CECDCAD619CF2
GO
Isoform USP25b (identifier: Q9UHP3-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     779-779: S → SIMMTPNMQGIIMAIGKSRSVYDRCGPEAGFFK

Show »
Length:1,087
Mass (Da):125,750
Checksum:i8F852D91651B2C6E
GO
Isoform USP25m (identifier: Q9UHP3-3) [UniParc]FASTAAdd to basket
Also known as: Muscle-specific isoform

The sequence of this isoform differs from the canonical sequence as follows:
     779-779: S → SKPENTTSQPLSNQRVVEVAIPHVGKFMIESKEGGYDDEIMMTPNMQGIIMAIGKSRSVYDRCGPEAGFFK

Show »
Length:1,125
Mass (Da):129,963
Checksum:i85236A294FFEFD60
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q96B65Q96B65_HUMAN
USP25 protein
USP25
450Annotation score:
H7C253H7C253_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP25
204Annotation score:
H7C1T8H7C1T8_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP25
229Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti544E → K in AAF32263 (PubMed:10644437).Curated1
Sequence conflicti544E → K in ACN76567 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_039632779S → SIMMTPNMQGIIMAIGKSRS VYDRCGPEAGFFK in isoform USP25b. 1 Publication1
Alternative sequenceiVSP_039631779S → SKPENTTSQPLSNQRVVEVA IPHVGKFMIESKEGGYDDEI MMTPNMQGIIMAIGKSRSVY DRCGPEAGFFK in isoform USP25m. 1 Publication1

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
CCDSiCCDS33515.1 [Q9UHP3-2]
CCDS63336.1 [Q9UHP3-3]
CCDS63337.1 [Q9UHP3-1]
RefSeqiNP_001269970.1, NM_001283041.1 [Q9UHP3-3]
NP_001269971.1, NM_001283042.1 [Q9UHP3-1]
NP_037528.3, NM_013396.4 [Q9UHP3-2]
UniGeneiHs.743994

Genome annotation databases

EnsembliENST00000285679; ENSP00000285679; ENSG00000155313 [Q9UHP3-2]
ENST00000285681; ENSP00000285681; ENSG00000155313 [Q9UHP3-1]
ENST00000400183; ENSP00000383044; ENSG00000155313 [Q9UHP3-3]
GeneIDi29761
KEGGihsa:29761
UCSCiuc002yjy.3 human [Q9UHP3-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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
CCDSiCCDS33515.1 [Q9UHP3-2]
CCDS63336.1 [Q9UHP3-3]
CCDS63337.1 [Q9UHP3-1]
RefSeqiNP_001269970.1, NM_001283041.1 [Q9UHP3-3]
NP_001269971.1, NM_001283042.1 [Q9UHP3-1]
NP_037528.3, NM_013396.4 [Q9UHP3-2]
UniGeneiHs.743994

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MUXNMR-A1-146[»]
5GP7X-ray1.50B1046-1055[»]
5O71X-ray3.28A1-714[»]
ProteinModelPortaliQ9UHP3
SMRiQ9UHP3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118895, 53 interactors
IntActiQ9UHP3, 26 interactors
MINTiQ9UHP3
STRINGi9606.ENSP00000285679

Protein family/group databases

MEROPSiC19.041

PTM databases

iPTMnetiQ9UHP3
PhosphoSitePlusiQ9UHP3

Polymorphism and mutation databases

DMDMi302393833

Proteomic databases

EPDiQ9UHP3
MaxQBiQ9UHP3
PaxDbiQ9UHP3
PeptideAtlasiQ9UHP3
PRIDEiQ9UHP3
ProteomicsDBi84385
84386 [Q9UHP3-1]
84387 [Q9UHP3-3]

Protocols and materials databases

DNASUi29761
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000285679; ENSP00000285679; ENSG00000155313 [Q9UHP3-2]
ENST00000285681; ENSP00000285681; ENSG00000155313 [Q9UHP3-1]
ENST00000400183; ENSP00000383044; ENSG00000155313 [Q9UHP3-3]
GeneIDi29761
KEGGihsa:29761
UCSCiuc002yjy.3 human [Q9UHP3-2]

Organism-specific databases

CTDi29761
DisGeNETi29761
EuPathDBiHostDB:ENSG00000155313.15
GeneCardsiUSP25
HGNCiHGNC:12624 USP25
HPAiHPA018297
HPA024142
MIMi604736 gene
neXtProtiNX_Q9UHP3
OpenTargetsiENSG00000155313
PharmGKBiPA37249
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1863 Eukaryota
COG5077 LUCA
GeneTreeiENSGT00390000016082
HOGENOMiHOG000007956
HOVERGENiHBG056030
InParanoidiQ9UHP3
KOiK11849
OMAiWAYIFDH
OrthoDBiEOG091G00QR
PhylomeDBiQ9UHP3
TreeFamiTF329035

Enzyme and pathway databases

ReactomeiR-HSA-5689880 Ub-specific processing proteases

Miscellaneous databases

ChiTaRSiUSP25 human
GenomeRNAii29761
PROiPR:Q9UHP3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155313 Expressed in 225 organ(s), highest expression level in sperm
CleanExiHS_USP21
HS_USP25
ExpressionAtlasiQ9UHP3 baseline and differential
GenevisibleiQ9UHP3 HS

Family and domain databases

InterProiView 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
PfamiView protein in Pfam
PF00443 UCH, 1 hit
PF02809 UIM, 2 hits
SMARTiView protein in SMART
SM00726 UIM, 1 hit
SUPFAMiSSF46934 SSF46934, 1 hit
SSF54001 SSF54001, 2 hits
PROSITEiView protein in PROSITE
PS50330 UIM, 1 hit
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBP25_HUMAN
AccessioniPrimary (citable) accession number: Q9UHP3
Secondary accession number(s): C0LSZ0, Q6DHZ9, Q9H9W1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 10, 2010
Last modified: September 12, 2018
This is version 175 of the entry and version 4 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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