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Q9UHP3 (UBP25_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:USP25
Synonyms:USP21
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1055 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.7 Ref.8 Ref.9 Ref.10

The muscle-specific isoform (USP25m)may have a role in the regulation of muscular differentiation and function. Ref.2 Ref.7 Ref.8 Ref.9 Ref.10

Catalytic activity

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).

Subunit structure

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. Ref.8 Ref.9 Ref.10 Ref.11

Subcellular location

Cytoplasm Ref.8 Ref.10.

Isoform USP25m: Cytoplasm By similarity. Nucleus By similarity. Note: Some transient punctuate nuclear location in myotubes during myocyte development By similarity. Ref.8 Ref.10

Tissue specificity

Isoform USB25ais 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 USB25bis found in all tissues except heart and skeletal muscle. Isoform USB25mis heart and skeletal muscle specific. Ref.1 Ref.7

Induction

The muscle-specific isoform (USP25m)is up-regulated during myocyte differentiation. Levels increase up to 100-fold towards completion of differentiation. Ref.8

Post-translational modification

Acetylated. Ref.10

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. Ref.9 Ref.10

Preferentially monoubiquitinated but can also be polyubiquitinated. Autodeubiquitinated. Ubiquitination activates the enzymatic activity either by preventing sumoylation or by allowing novel interactions. Ref.9 Ref.10

Phosphorylation in the C-terminal by SYK regulates USP25 cellular levels.

Sequence similarities

Belongs to the peptidase C19 family.

Contains 1 UBA-like domain.

Contains 2 UIM (ubiquitin-interacting motif) repeats.

Contains 1 USP domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform USP25a (identifier: Q9UHP3-2)

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.
Isoform USP25b (identifier: Q9UHP3-1)

The sequence of this isoform differs from the canonical sequence as follows:
     779-779: S → SIMMTPNMQGIIMAIGKSRSVYDRCGPEAGFFK
Isoform USP25m (identifier: Q9UHP3-3)

Also known as: Muscle-specific isoform;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10551055Ubiquitin carboxyl-terminal hydrolase 25
PRO_0000080653

Regions

Domain14 – 5744UBA-like
Repeat97 – 11620UIM 1
Repeat123 – 14018UIM 2
Domain169 – 657489USP
Region77 – 10226SUMO interaction domain (SIM)
Coiled coil541 – 57838 Potential
Coiled coil684 – 71734 Potential
Motif89 – 957Required for SUMO paralog-specific binding

Sites

Active site1781 Ref.10
Active site5991 By similarity
Active site6071 By similarity

Amino acid modifications

Modified residue7401Phosphotyrosine Ref.11
Cross-link99Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.9 Ref.10
Cross-link99Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate

Natural variations

Alternative sequence7791S → SIMMTPNMQGIIMAIGKSRS VYDRCGPEAGFFK in isoform USP25b.
VSP_039632
Alternative sequence7791S → SKPENTTSQPLSNQRVVEVA IPHVGKFMIESKEGGYDDEI MMTPNMQGIIMAIGKSRSVY DRCGPEAGFFK in isoform USP25m.
VSP_039631

Experimental info

Mutagenesis911V → A: No interaction with SUMO3; when associated with A-92. Ref.9
Mutagenesis921I → A: No interaction with SUMO3; when associated with A-91. Ref.9
Mutagenesis991K → R: Abolishes sumoylation. Decreased enzymatic activity. Ref.9 Ref.10
Mutagenesis1781C → S: Abrogates deubiquitinating activity. No effect on homo- or oligomerization. Ref.10
Mutagenesis7401Y → F: No effect on interaction with SYK. Ref.11
Mutagenesis8781T → I: No effect on interaction with SYK. Ref.11
Mutagenesis8801Y → F: No effect on interaction with SYK. Ref.11
Mutagenesis8831I → S: No effect on interaction with SYK. Ref.11
Sequence conflict5441E → K in AAF32263. Ref.1
Sequence conflict5441E → K in ACN76567. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform USP25a [UniParc].

Last modified August 10, 2010. Version 4.
Checksum: 0B9CECDCAD619CF2

FASTA1,055122,218
        10         20         30         40         50         60 
MTVEQNVLQQ SAAQKHQQTF LNQLREITGI NDTQILQQAL KDSNGNLELA VAFLTAKNAK 

        70         80         90        100        110        120 
TPQQEETTYY QTALPGNDRY ISVGSQADTN VIDLTGDDKD DLQRAIALSL AESNRAFRET 

       130        140        150        160        170        180 
GITDEEQAIS RVLEASIAEN KACLKRTPTE VWRDSRNPYD RKRQDKAPVG LKNVGNTCWF 

       190        200        210        220        230        240 
SAVIQSLFNL LEFRRLVLNY KPPSNAQDLP RNQKEHRNLP FMRELRYLFA LLVGTKRKYV 

       250        260        270        280        290        300 
DPSRAVEILK DAFKSNDSQQ QDVSEFTHKL LDWLEDAFQM KAEEETDEEK PKNPMVELFY 

       310        320        330        340        350        360 
GRFLAVGVLE GKKFENTEMF GQYPLQVNGF KDLHECLEAA MIEGEIESLH SENSGKSGQE 

       370        380        390        400        410        420 
HWFTELPPVL TFELSRFEFN QALGRPEKIH NKLEFPQVLY LDRYMHRNRE ITRIKREEIK 

       430        440        450        460        470        480 
RLKDYLTVLQ QRLERYLSYG SGPKRFPLVD VLQYALEFAS SKPVCTSPVD DIDASSPPSG 

       490        500        510        520        530        540 
SIPSQTLPST TEQQGALSSE LPSTSPSSVA AISSRSVIHK PFTQSRIPPD LPMHPAPRHI 

       550        560        570        580        590        600 
TEEELSVLES CLHRWRTEIE NDTRDLQESI SRIHRTIELM YSDKSMIQVP YRLHAVLVHE 

       610        620        630        640        650        660 
GQANAGHYWA YIFDHRESRW MKYNDIAVTK SSWEELVRDS FGGYRNASAY CLMYINDKAQ 

       670        680        690        700        710        720 
FLIQEEFNKE TGQPLVGIET LPPDLRDFVE EDNQRFEKEL EEWDAQLAQK ALQEKLLASQ 

       730        740        750        760        770        780 
KLRESETSVT TAQAAGDPEY LEQPSRSDFS KHLKEETIQI ITKASHEHED KSPETVLQSA 

       790        800        810        820        830        840 
IKLEYARLVK LAQEDTPPET DYRLHHVVVY FIQNQAPKKI IEKTLLEQFG DRNLSFDERC 

       850        860        870        880        890        900 
HNIMKVAQAK LEMIKPEEVN LEEYEEWHQD YRKFRETTMY LIIGLENFQR ESYIDSLLFL 

       910        920        930        940        950        960 
ICAYQNNKEL LSKGLYRGHD EELISHYRRE CLLKLNEQAA ELFESGEDRE VNNGLIIMNE 

       970        980        990       1000       1010       1020 
FIVPFLPLLL VDEMEEKDIL AVEDMRNRWC SYLGQEMEPH LQEKLTDFLP KLLDCSMEIK 

      1030       1040       1050 
SFHEPPKLPS YSTHELCERF ARIMLSLSRT PADGR 

« Hide

Isoform USP25b [UniParc].

Checksum: 8F852D91651B2C6E
Show »

FASTA1,087125,750
Isoform USP25m (Muscle-specific isoform) [UniParc].

Checksum: 85236A294FFEFD60
Show »

FASTA1,125129,963

References

« Hide 'large scale' references
[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] (ISOFORMS USP25A AND USP25B), TISSUE SPECIFICITY.
Tissue: Fetal brain.
[2]"Narrowing of the region of allelic loss in 21q11-21 in squamous non-small cell lung carcinoma and cloning of a novel ubiquitin-specific protease gene from the deleted segment."
Groet J., Ives J.H., Jones T.A., Danton M., Flomen R.H., Sheer D., Hrascan R., Pavelic K., Nizetic D.
Genes Chromosomes Cancer 27:153-161(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM USP25A), FUNCTION.
[3]Valero R., Bosch-Comas A., Denuc A., Gonzalez-Duarte R., Marfany G.
Submitted (FEB-2009) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM USP25M).
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORM USP25A).
Tissue: Placenta.
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 319-1055 (ISOFORM USP25A).
[7]"Characterization of alternatively spliced products and tissue-specific isoforms of USP28 and USP25."
Valero R., Bayes M., Francisca Sanchez-Font M., Gonzalez-Angulo O., Gonzalez-Duarte R., Marfany G.
Genome Biol. 2:RESEARCH0043.1-RESEARCH0043.10(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, FUNCTION, TISSUE SPECIFICITY.
[8]"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, INTERACTION WITH ACTA1; FLNC; GAPDH AND MYBPC1, INDUCTION, SUBCELLULAR LOCATION, POSSIBLE FUNCTION.
[9]"Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25."
Meulmeester E., Kunze M., Hsiao H.H., Urlaub H., Melchior F.
Mol. Cell 30:610-619(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-99, FUNCTION, INTERACTION WITH SUMO1; SUMO3 AND UBIQUITIN, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF VAL-91; ILE-92 AND LYS-99.
[10]"The UBA-UIM domains of the USP25 regulate the enzyme ubiquitination state and modulate substrate recognition."
Denuc A., Bosch-Comas A., Gonzalez-Duarte R., Marfany G.
PLoS ONE 4:E5571-E5571(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-99, DEUBIQUITINATION, ACTIVE SITE CYS-178, ACETYLATION, PHOSPHORYLATION, SUMOYLATION, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, MUTAGENESIS OF LYS-99 AND CYS-178.
[11]"Functional interaction between the ubiquitin-specific protease 25 and the SYK tyrosine kinase."
Cholay M., Reverdy C., Benarous R., Colland F., Daviet L.
Exp. Cell Res. 316:667-675(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SYK, PHOSPHORYLATION AT TYR-740, MUTAGENESIS OF TYR-740; THR-878; TYR-880 AND ILE-883.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001269970.1. NM_001283041.1.
NP_001269971.1. NM_001283042.1.
NP_037528.3. NM_013396.4.
UniGeneHs.743994.

3D structure databases

ProteinModelPortalQ9UHP3.
SMRQ9UHP3. Positions 1-138, 140-411, 591-676.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118895. 34 interactions.
IntActQ9UHP3. 18 interactions.
MINTMINT-1188384.
STRING9606.ENSP00000285679.

Protein family/group databases

MEROPSC19.041.

PTM databases

PhosphoSiteQ9UHP3.

Polymorphism databases

DMDM302393833.

Proteomic databases

PaxDbQ9UHP3.
PRIDEQ9UHP3.

Protocols and materials databases

DNASU29761.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000285679; ENSP00000285679; ENSG00000155313. [Q9UHP3-2]
ENST00000285681; ENSP00000285681; ENSG00000155313. [Q9UHP3-1]
ENST00000400183; ENSP00000383044; ENSG00000155313. [Q9UHP3-3]
GeneID29761.
KEGGhsa:29761.
UCSCuc002yjy.1. human. [Q9UHP3-2]
uc002yjz.1. human. [Q9UHP3-1]
uc011aby.1. human. [Q9UHP3-3]

Organism-specific databases

CTD29761.
GeneCardsGC21P017102.
HGNCHGNC:12624. USP25.
HPAHPA018297.
HPA024142.
MIM604736. gene.
neXtProtNX_Q9UHP3.
PharmGKBPA37249.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5077.
HOGENOMHOG000007956.
HOVERGENHBG056030.
InParanoidQ9UHP3.
KOK11849.
OMASRSVIHK.
OrthoDBEOG761BSZ.
PhylomeDBQ9UHP3.
TreeFamTF329035.

Gene expression databases

ArrayExpressQ9UHP3.
BgeeQ9UHP3.
CleanExHS_USP21.
HS_USP25.
GenevestigatorQ9UHP3.

Family and domain databases

InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR009060. UBA-like.
IPR003903. Ubiquitin-int_motif.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF00443. UCH. 1 hit.
PF02809. UIM. 2 hits.
[Graphical view]
SMARTSM00726. UIM. 1 hit.
[Graphical view]
SUPFAMSSF46934. SSF46934. 1 hit.
PROSITEPS50330. UIM. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUSP25. human.
GenomeRNAi29761.
NextBio52254.
PROQ9UHP3.
SOURCESearch...

Entry information

Entry nameUBP25_HUMAN
AccessionPrimary (citable) accession number: Q9UHP3
Secondary accession number(s): C0LSZ0, Q6DHZ9, Q9H9W1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 10, 2010
Last modified: April 16, 2014
This is version 138 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM