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Q9Y4E8 (UBP15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
Unph-2
Unph4
Gene names
Name:USP15
Synonyms:KIAA0529
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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 (Ref.23). 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 (Ref.26). 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. Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway. Ref.12 Ref.14 Ref.17 Ref.18 Ref.19 Ref.23 Ref.26

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). Ref.10 Ref.12 Ref.23 Ref.26

Subunit structure

A homodimer structure has been reported; however it is unclear whether the protein form a homodimer in vivo (Ref.30). 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. Interacts with human papillomavirus type 16 protein E6. Ref.12 Ref.19 Ref.23 Ref.26

Subcellular location

Cytoplasm. Nucleus Ref.23.

Tissue specificity

Expressed in skeletal muscle, kidney, heart, placenta, liver, thymus, lung, and ovary, with little or no expression in other tissues.

Post-translational modification

Phosphorylated. Phosphorylation protects against ubiquitination and subsequent degradation by the proteasome. Ref.12

Ubiquitinated, leading to degradation by the proteasome. Ref.12

Sequence similarities

Belongs to the peptidase C19 family.

Contains 1 DUSP domain.

Contains 1 USP domain.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   Molecular functionHydrolase
Protease
Thiol protease
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from direct assay Ref.23. Source: UniProtKB

monoubiquitinated protein deubiquitination

Inferred from direct assay Ref.23. Source: UniProtKB

negative regulation of transforming growth factor beta receptor signaling pathway

Traceable author statement. Source: Reactome

pathway-restricted SMAD protein phosphorylation

Inferred from mutant phenotype Ref.26. Source: UniProtKB

protein deubiquitination

Inferred from direct assay Ref.12Ref.26. Source: UniProtKB

transforming growth factor beta receptor signaling pathway

Inferred from direct assay Ref.23. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcytoplasm

Inferred from direct assay Ref.23. Source: UniProtKB

nucleus

Inferred from direct assay Ref.23. Source: UniProtKB

   Molecular_functionSMAD binding

Inferred from physical interaction Ref.23Ref.26. Source: UniProtKB

cysteine-type endopeptidase activity

Inferred from mutant phenotype Ref.23Ref.26. Source: UniProtKB

identical protein binding

Inferred from physical interaction Ref.30. Source: IntAct

transforming growth factor beta receptor binding

Inferred from physical interaction Ref.26. Source: UniProtKB

ubiquitin thiolesterase activity

Inferred from direct assay Ref.23Ref.26. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from direct assay Ref.12Ref.23Ref.26. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself5EBI-1043104,EBI-1043104

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y4E8-1)

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: Q9Y4E8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     228-256: Missing.
Isoform 3 (identifier: Q9Y4E8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     217-256: DGTWPRGPSTPKSPGASNFSTLPKISPSSLSNNYNNMNNR → QKNEDGTWPRGPSTP
Isoform 4 (identifier: Q9Y4E8-4)

The sequence of this isoform differs from the canonical sequence as follows:
     229-235: SPGASNF → KPLEQSC
     236-981: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 981980Ubiquitin carboxyl-terminal hydrolase 15
PRO_0000080641

Regions

Domain7 – 118112DUSP
Domain289 – 933645USP

Sites

Active site2981Nucleophile
Active site8911Proton acceptor By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.8 Ref.16 Ref.25 Ref.27
Modified residue2291Phosphoserine Ref.13 Ref.15 Ref.20 Ref.21 Ref.24
Modified residue2421Phosphoserine Ref.21
Modified residue9611Phosphoserine Ref.15 Ref.21
Modified residue9651Phosphoserine Ref.15 Ref.21

Natural variations

Alternative sequence217 – 25640DGTWP…NMNNR → QKNEDGTWPRGPSTP in isoform 3.
VSP_005260
Alternative sequence228 – 25629Missing in isoform 2.
VSP_005261
Alternative sequence229 – 2357SPGASNF → KPLEQSC in isoform 4.
VSP_045165
Alternative sequence236 – 981746Missing in isoform 4.
VSP_045166

Experimental info

Mutagenesis2981C → A: Loss of enzyme activity. Ref.19 Ref.23 Ref.26
Mutagenesis8121C → A: Loss of activity towards polyubiquitin. Ref.12 Ref.18
Sequence conflict5591T → A in AAG28973. Ref.9
Sequence conflict7471S → F in AAI25124. Ref.7
Sequence conflict9681N → H in AAG28973. Ref.9

Secondary structure

......................................... 981
Helix Strand Turn

Details...

Sequences

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

Last modified February 12, 2003. Version 3.
Checksum: E81FEB9DE57F7089

FASTA981112,419
        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 IEKEIRKIFS IPDEKETRLW 

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

       250        260        270        280        290        300 
ISPSSLSNNY NNMNNRNVKN 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 KKERTLEVYL 

       490        500        510        520        530        540 
VRMDPLTKPM QYKVVVPKIG NILDLCTALS ALSGIPADKM IVTDIYNHRF HRIFAMDENL 

       550        560        570        580        590        600 
SSIMERDDIY VFEININRTE DTEHVIIPVC LREKFRHSSY THHTGSSLFG QPFLMAVPRN 

       610        620        630        640        650        660 
NTEDKLYNLL LLRMCRYVKI STETEETEGS LHCCKDQNIN GNGPNGIHEE GSPSEMETDE 

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

       730        740        750        760        770        780 
NTDINYIKDD TRHIRFDDRQ LRLDERSFLA LDWDPDLKKR YFDENAAEDF EKHESVEYKP 

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

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

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

       970        980 
SDEDSNDNDN DIENENCMHT N 

« Hide

Isoform 2 [UniParc].

Checksum: 852ED3768FB5725A
Show »

FASTA952109,297
Isoform 3 [UniParc].

Checksum: F9F83D3886404B11
Show »

FASTA956109,796
Isoform 4 [UniParc].

Checksum: F69B0D2783E2A443
Show »

FASTA23527,094

References

« Hide 'large scale' references
[1]"Identification and characterization of a new human deubiquitinating enzyme Unph4."
Kim K.I., Nagase T., Chung C.H.
Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Brain.
[2]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[3]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[4]"A catalogue of genes in the human dermal papilla cells as identified by expressed sequence tags."
Kim M.K., Kim Y.H., Seo J.M., Lee H.M., Chung H.J., Sohn M.Y., Hwang S.Y., Im S.U., Jung E.J., Lee J.H., Kim J.C.
Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Hair follicle dermal papilla.
[5]"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] (ISOFORM 4).
Tissue: Placenta.
[6]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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] (ISOFORMS 2 AND 4).
Tissue: Brain and Lung.
[8]Bienvenut W.V., Matallanas D., Cooper W.N., Kolch W.
Submitted (JUL-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-21; 475-482 AND 924-932, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Mammary carcinoma.
[9]"Cloning and identification of human Unph-2."
Kimura Y., Saya H., Nakao M.
Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-981 (ISOFORM 3).
Tissue: Fetal brain.
[10]"Identification, functional characterization, and chromosomal localization of USP15, a novel human ubiquitin-specific protease related to the UNP oncoprotein, and a systematic nomenclature for human ubiquitin-specific proteases."
Baker R.T., Wang X.-W., Woollatt E., White J.A., Sutherland G.R.
Genomics 59:264-274(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION (ISOFORM 2), CATALYTIC ACTIVITY.
[11]"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: ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
[12]"The zinc finger of the CSN-associated deubiquitinating enzyme USP15 is essential to rescue the E3 ligase Rbx1."
Hetfeld B.K., Helfrich A., Kapelari B., Scheel H., Hofmann K., Guterman A., Glickman M., Schade R., Kloetzel P.M., Dubiel W.
Curr. Biol. 15:1217-1221(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-812, IDENTIFICATION IN A COMPLEX WITH THE COP9 SIGNALOSOME, PHOSPHORYLATION, UBIQUITINATION.
[13]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"CSN controls NF-kappaB by deubiquitinylation of IkappaBalpha."
Schweitzer K., Bozko P.M., Dubiel W., Naumann M.
EMBO J. 26:1532-1541(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229; SER-961 AND SER-965, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"COP9 signalosome interacts ATP-dependently with p97/valosin-containing protein (VCP) and controls the ubiquitination status of proteins bound to p97/VCP."
Cayli S., Klug J., Chapiro J., Frohlich S., Krasteva G., Orel L., Meinhardt A.
J. Biol. Chem. 284:34944-34953(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[18]"The COP9 signalosome mediates beta-catenin degradation by deneddylation and blocks adenomatous polyposis coli destruction via USP15."
Huang X., Langelotz C., Hetfeld-Pechoc B.K., Schwenk W., Dubiel W.
J. Mol. Biol. 391:691-702(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-812.
[19]"The ubiquitin-specific peptidase USP15 regulates human papillomavirus type 16 E6 protein stability."
Vos R.M., Altreuter J., White E.A., Howley P.M.
J. Virol. 83:8885-8892(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-298, INTERACTION WITH HUMAN PAPILLOMAVIRUS TYPE 16 PROTEIN E6.
[20]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[21]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229; SER-242; SER-961 AND SER-965, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"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].
[23]"USP15 is a deubiquitylating enzyme for receptor-activated SMADs."
Inui M., Manfrin A., Mamidi A., Martello G., Morsut L., Soligo S., Enzo E., Moro S., Polo S., Dupont S., Cordenonsi M., Piccolo S.
Nat. Cell Biol. 13:1368-1375(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH SMAD1; SMAD2 AND SMAD3, MUTAGENESIS OF CYS-298.
[24]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-229, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"USP15 stabilizes TGF-beta receptor I and promotes oncogenesis through the activation of TGF-beta signaling in glioblastoma."
Eichhorn P.J., Rodon L., Gonzalez-Junca A., Dirac A., Gili M., Martinez-Saez E., Aura C., Barba I., Peg V., Prat A., Cuartas I., Jimenez J., Garcia-Dorado D., Sahuquillo J., Bernards R., Baselga J., Seoane J.
Nat. Med. 18:429-435(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TGFBR1 AND SMAD7, MUTAGENESIS OF CYS-298.
[27]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"Solution structure of the human ubiquitin-specific protease 15 DUSP domain."
de Jong R.N., Ab E., Diercks T., Truffault V., Danieels M., Kaptein R., Folkers G.E.
J. Biol. Chem. 281:5026-5031(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-120.
[29]"Structure of the USP15 N-terminal domains: a beta-hairpin mediates close association between the DUSP and UBL domains."
Harper S., Besong T.M., Emsley J., Scott D.J., Dreveny I.
Biochemistry 50:7995-8004(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-222.
[30]"Structural variability of the ubiquitin specific protease DUSP-UBL double domains."
Elliott P.R., Liu H., Pastok M.W., Grossmann G.J., Rigden D.J., Clague M.J., Urbe S., Barsukov I.L.
FEBS Lett. 585:3385-3390(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-223.
[31]"Crystal structure of the human ubiquitin-specific protease 15 DUSP domain."
Structural genomics consortium (SGC)
Submitted (APR-2010) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 1-133.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF106069 mRNA. Translation: AAD52099.1.
AB011101 mRNA. Translation: BAA25455.2.
AF153604 mRNA. Translation: AAD41086.1.
AK023703 mRNA. Translation: BAB14648.1.
AK292337 mRNA. Translation: BAF85026.1.
AC048342 Genomic DNA. No translation available.
AC079035 Genomic DNA. No translation available.
AC117370 Genomic DNA. No translation available.
BC020688 mRNA. Translation: AAH20688.1.
BC063454 mRNA. Translation: AAH63454.1.
BC125123 mRNA. Translation: AAI25124.1.
AF013990 mRNA. Translation: AAG28973.1.
RefSeqNP_001239007.1. NM_001252078.1.
NP_001239008.1. NM_001252079.1.
NP_006304.1. NM_006313.2.
UniGeneHs.434951.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1W6VNMR-A1-120[»]
3LMNX-ray2.15A/B1-133[»]
3PPAX-ray2.35A6-223[»]
3PV1X-ray2.60A/B1-223[»]
3T9LX-ray1.50A1-222[»]
4A3OX-ray2.20A/B6-223[»]
4A3PX-ray1.40A6-223[»]
ProteinModelPortalQ9Y4E8.
SMRQ9Y4E8. Positions 6-222, 285-470, 786-934.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115283. 105 interactions.
DIPDIP-50239N.
IntActQ9Y4E8. 35 interactions.
MINTMINT-4542165.
STRING9606.ENSP00000258123.

Protein family/group databases

MEROPSC19.022.

PTM databases

PhosphoSiteQ9Y4E8.

Polymorphism databases

DMDM28381406.

Proteomic databases

PaxDbQ9Y4E8.
PRIDEQ9Y4E8.

Protocols and materials databases

DNASU9958.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000280377; ENSP00000280377; ENSG00000135655. [Q9Y4E8-1]
ENST00000312635; ENSP00000309240; ENSG00000135655. [Q9Y4E8-4]
ENST00000353364; ENSP00000258123; ENSG00000135655. [Q9Y4E8-2]
GeneID9958.
KEGGhsa:9958.
UCSCuc001sra.3. human.
uc001srb.2. human. [Q9Y4E8-2]
uc001src.2. human. [Q9Y4E8-1]

Organism-specific databases

CTD9958.
GeneCardsGC12P062706.
H-InvDBHIX0010773.
HGNCHGNC:12613. USP15.
HPAHPA006237.
MIM604731. gene.
neXtProtNX_Q9Y4E8.
PharmGKBPA37239.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5560.
HOGENOMHOG000264375.
HOVERGENHBG000864.
InParanoidQ9Y4E8.
KOK11835.
OMAQMWSGKY.
OrthoDBEOG77Q4VW.
PhylomeDBQ9Y4E8.
TreeFamTF106276.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

ArrayExpressQ9Y4E8.
BgeeQ9Y4E8.
CleanExHS_USP15.
GenevestigatorQ9Y4E8.

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.
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.
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. human.
EvolutionaryTraceQ9Y4E8.
GeneWikiUSP15.
GenomeRNAi9958.
NextBio37576.
PROQ9Y4E8.
SOURCESearch...

Entry information

Entry nameUBP15_HUMAN
AccessionPrimary (citable) accession number: Q9Y4E8
Secondary accession number(s): Q08AL5 expand/collapse secondary AC list , Q9H8G9, Q9HCA6, Q9UNP0, Q9Y5B5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: February 12, 2003
Last modified: April 16, 2014
This is version 139 of the entry and version 3 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM