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Q8R5H1 (UBP15_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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 15

EC=3.4.19.12
Alternative name(s):
Deubiquitinating enzyme 15
Ubiquitin thioesterase 15
Ubiquitin-specific-processing protease 15
Gene names
Name:Usp15
Synonyms:Kiaa0529
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length981 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling and NF-kappa-B pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes. According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal. Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP By similarity.

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

Identified in a complex with the COP9 signalosome complex (CSN). Interacts with SMAD1, SMAD2 and SMAD3; the interaction is direct. Forms a complex with SMURF2 and SMAD7. Interacts with TGFBR1 By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Tissue specificity

Widely expressed with highest levels in testis, heart and liver. Ref.1

Post-translational modification

Phosphorylated. Phosphorylation protects against ubiquitination and subsequent degradation by the proteasome By similarity.

Ubiquitinated, leading to degradation by the proteasome By similarity.

Sequence similarities

Belongs to the peptidase C19 family.

Contains 1 DUSP domain.

Contains 1 USP domain.

Sequence caution

The sequence BAC65583.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence EDL24441.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q8R5H1-1)

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 2 (identifier: Q8R5H1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     18-25: TLLKTSLR → DAWLKPRSG
     228-256: Missing.
Isoform 3 (identifier: Q8R5H1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     229-981: Missing.
Isoform 4 (identifier: Q8R5H1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     209-227: LVIEQKNEDGTWPRGPSTP → PRCIQFFNFTKDLSFISIK
     228-981: Missing.
Isoform 5 (identifier: Q8R5H1-5)

The sequence of this isoform differs from the canonical sequence as follows:
     228-256: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 981980Ubiquitin carboxyl-terminal hydrolase 15
PRO_0000080642

Regions

Domain7 – 118112DUSP
Domain289 – 933645USP

Sites

Active site2981Nucleophile By similarity UniProtKB Q9Y4E8
Active site8911Proton acceptor By similarity UniProtKB Q9Y4E8

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue2291Phosphoserine Ref.6
Modified residue2421Phosphoserine By similarity
Modified residue9611Phosphoserine By similarity
Modified residue9651Phosphoserine By similarity

Natural variations

Alternative sequence18 – 258TLLKTSLR → DAWLKPRSG in isoform 2. Ref.1
VSP_005262
Alternative sequence209 – 22719LVIEQ…GPSTP → PRCIQFFNFTKDLSFISIK in isoform 4.
VSP_005265
Alternative sequence228 – 981754Missing in isoform 4.
VSP_005266
Alternative sequence228 – 25629Missing in isoform 2 and isoform 5. Ref.1
VSP_005263
Alternative sequence229 – 981753Missing in isoform 3.
VSP_005264

Experimental info

Sequence conflict1301E → G in BAE40593. Ref.3
Sequence conflict1581I → M in BAE36413. Ref.3
Sequence conflict1841M → V in AAH50042. Ref.5
Sequence conflict6621D → G in AAH50042. Ref.5
Sequence conflict8001K → E in AAH50042. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2002. Version 1.
Checksum: 6D5377C3FEA6E40A

FASTA981112,325
        10         20         30         40         50         60 
MAEGGAADLD TQRSDIATLL KTSLRKGDTW YLVDSRWFKQ WKKYVGFDSW DKYQMGDQNV 

        70         80         90        100        110        120 
YPGPIDNSGL LKDGDAQSLK EHLIDELDYI LLPTEGWNKL VSWYTLMEGQ EPIARKVVEQ 

       130        140        150        160        170        180 
GMFVKHCKVE VYLTELKLCE NGNMNNVVTR RFSKADTIDT IEKEIRKIFN IPDEKEARLW 

       190        200        210        220        230        240 
NKYMSNTFEP LNKPDSTIQD AGLYQGQVLV IEQKNEDGTW PRGPSTPKSP GASNFSTLPK 

       250        260        270        280        290        300 
ISPSSLSNNY NNINNRNVKN SNYCLPSYTA YKNYDYSEPG RNNEQPGLCG LSNLGNTCFM 

       310        320        330        340        350        360 
NSAIQCLSNT PPLTEYFLND KYQEELNFDN PLGMRGEIAK SYAELIKQMW SGKFSYVTPR 

       370        380        390        400        410        420 
AFKTQVGRFA PQFSGYQQQD CQELLAFLLD GLHEDLNRIR KKPYIQLKDA DGRPDKVVAE 

       430        440        450        460        470        480 
EAWENHLKRN DSIIVDIFHG LFKSTLVCPE CAKISVTFDP FCYLTLPLPM KKERSLEVYL 

       490        500        510        520        530        540 
VRMDPLAKPM QYKVIVPKIG NILDLCTALS ALSGVPADKM IVTDIYNHRF HRIFAVDENL 

       550        560        570        580        590        600 
SSIMERDDIY VFEININRAE DTEHVVIPVC LREKFRHSSY THHTGSSLFG QPFLMAIPRN 

       610        620        630        640        650        660 
NTEDKLYNLL LLRMCRYVKM STETEETDGH LRCCEDQNIN GNGPNGLHEE GSPSEMETDE 

       670        680        690        700        710        720 
PDDESSQDQE LPSENENSQS EDSVGGDNDS ENGLCTEETC KGQLTGHKKR LFTFQFNNLG 

       730        740        750        760        770        780 
NNDINYIKDD TSHIRFDDRQ LRLDERSFLA LDWDPDLKKR YFDENAAEDF EKHESVEYKP 

       790        800        810        820        830        840 
PKRPFVKLKD CIELFTTKEK LGAEDPWYCP NCKEHQQATK KLDLWSLPPV LVVHLKRFSY 

       850        860        870        880        890        900 
SRYMRDKLDT LVDFPISDLD MSEFLINPNA GPCRYNLIAV SNHYGGMGGG HYTAFAKNKD 

       910        920        930        940        950        960 
DGKWYYFDDS SVSTASEDQI VSKAAYVLFY QRQDTFSGTG FFPLDRETKG ASAATGIPLE 

       970        980 
SDEDSNDNDN DLENENCMHT N 

« Hide

Isoform 2 [UniParc].

Checksum: D56685B92C029188
Show »

FASTA953109,318
Isoform 3 [UniParc].

Checksum: 43F1F4F48122703B
Show »

FASTA22826,305
Isoform 4 [UniParc].

Checksum: A92B80D4BEE7E26E
Show »

FASTA22726,357
Isoform 5 [UniParc].

Checksum: D779A1FB3667963A
Show »

FASTA952109,220

References

« Hide 'large scale' references
[1]"Isolation and characterization of the mouse ubiquitin-specific protease Usp15."
Angelats C., Wang X.-W., Jermiin L.S., Copeland N.G., Jenkins N.A., Baker R.T.
Mamm. Genome 14:31-46(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
Strain: C57BL/6.
[2]"Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H.
DNA Res. 10:35-48(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
Tissue: Brain.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3; 4 AND 5).
Strain: C57BL/6J.
Tissue: Amnion, Corpora quadrigemina, Testis and Thymus.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-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 1).
Tissue: Trophoblast stem cell.
[6]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF468037 mRNA. Translation: AAL77418.1.
AK046332 mRNA. Translation: BAC32683.1.
AK083303 mRNA. Translation: BAC38854.1.
AK133852 mRNA. Translation: BAE21887.1.
AK145749 mRNA. Translation: BAE26626.1.
AK161469 mRNA. Translation: BAE36413.1.
AK168755 mRNA. Translation: BAE40593.1.
AK122301 mRNA. Translation: BAC65583.1. Different initiation.
CH466578 Genomic DNA. Translation: EDL24441.1. Different initiation.
BC050042 mRNA. Translation: AAH50042.1.
CCDSCCDS24217.1. [Q8R5H1-1]
RefSeqNP_081880.2. NM_027604.3. [Q8R5H1-1]
XP_006513287.1. XM_006513224.1. [Q8R5H1-5]
UniGeneMm.244209.
Mm.470032.

3D structure databases

ProteinModelPortalQ8R5H1.
SMRQ8R5H1. Positions 2-222, 285-470, 786-934.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8R5H1. 1 interaction.
MINTMINT-4139191.

Protein family/group databases

MEROPSC19.022.

PTM databases

PhosphoSiteQ8R5H1.

Proteomic databases

MaxQBQ8R5H1.
PaxDbQ8R5H1.
PRIDEQ8R5H1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020334; ENSMUSP00000020334; ENSMUSG00000020124. [Q8R5H1-1]
GeneID14479.
KEGGmmu:14479.
UCSCuc007hgn.1. mouse. [Q8R5H1-1]
uc007hgt.1. mouse. [Q8R5H1-3]
uc011xpf.1. mouse. [Q8R5H1-4]

Organism-specific databases

CTD9958.
MGIMGI:101857. Usp15.
RougeSearch...

Phylogenomic databases

eggNOGCOG5560.
GeneTreeENSGT00670000097750.
HOGENOMHOG000264375.
HOVERGENHBG000864.
InParanoidQ8R5H1.
KOK11835.
OMARYVKTCT.
OrthoDBEOG77Q4VW.
PhylomeDBQ8R5H1.
TreeFamTF106276.

Gene expression databases

ArrayExpressQ8R5H1.
BgeeQ8R5H1.
CleanExMM_USP15.
GenevestigatorQ8R5H1.

Family and domain databases

Gene3D3.30.2230.10. 1 hit.
InterProIPR006615. Pept_C19_DUSP.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR013792. RNA3'P_cycl/enolpyr_Trfase_a/b.
IPR028135. Ub_USP-typ.
IPR029071. Ubiquitin-rel_dom.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF06337. DUSP. 1 hit.
PF14836. Ubiquitin_3. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view]
SMARTSM00695. DUSP. 1 hit.
[Graphical view]
SUPFAMSSF143791. SSF143791. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF55205. SSF55205. 1 hit.
PROSITEPS51283. DUSP. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUSP15. mouse.
NextBio286150.
PROQ8R5H1.
SOURCESearch...

Entry information

Entry nameUBP15_MOUSE
AccessionPrimary (citable) accession number: Q8R5H1
Secondary accession number(s): Q3TGF5 expand/collapse secondary AC list , Q3TTB2, Q3UL25, Q3UZH0, Q80TY6, Q80UK9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 22, 2003
Last sequence update: June 1, 2002
Last modified: July 9, 2014
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot