Q9Y4E8 (UBP15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	981 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.22). 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.24). 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.16 Ref.17 Ref.18 Ref.22 Ref.24
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.22 Ref.24
Subunit structure	A homodimer structure has been reported; however it is unclear whether the protein form a homodimer in vivo (Ref.27). 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.18 Ref.22 Ref.24
Subcellular location	Cytoplasm. Nucleus Ref.22.
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.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Hydrolase Protease Thiol protease
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from direct assay Ref.22. Source: UniProtKB monoubiquitinated protein deubiquitination Inferred from direct assay Ref.22. 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.24. Source: UniProtKB transforming growth factor beta receptor signaling pathway Inferred from direct assay Ref.22. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from direct assay Ref.22. Source: UniProtKB nucleus Inferred from direct assay Ref.22. Source: UniProtKB
Molecular_function	cysteine-type endopeptidase activity Inferred from mutant phenotype Ref.22Ref.24. Source: UniProtKB ubiquitin thiolesterase activity Inferred from direct assay Ref.22Ref.24. Source: UniProtKB ubiquitin-specific protease activity Inferred from direct assay Ref.12Ref.22Ref.24. Source: UniProtKB
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 981

980

Ubiquitin carboxyl-terminal hydrolase 15

PRO_0000080641

Regions

Domain

7 – 118

112

DUSP

Sites

Active site

298

1

Nucleophile

Active site

891

1

Proton acceptor By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8

Modified residue

229

1

Phosphoserine Ref.13 Ref.15 Ref.19 Ref.20 Ref.23

Modified residue

242

1

Phosphoserine Ref.20

Modified residue

961

1

Phosphoserine Ref.15 Ref.20

Modified residue

965

1

Phosphoserine Ref.15 Ref.20

Natural variations

Alternative sequence

217 – 256

40

DGTWP…NMNNR → QKNEDGTWPRGPSTP in isoform 3.

VSP_005260

Alternative sequence

228 – 256

29

Missing in isoform 2.

VSP_005261

Alternative sequence

229 – 235

7

SPGASNF → KPLEQSC in isoform 4.

VSP_045165

Alternative sequence

236 – 981

746

Missing in isoform 4.

VSP_045166

Experimental info

Mutagenesis

298

1

C → A: Loss of enzyme activity. Ref.18 Ref.22 Ref.24

Mutagenesis

812

1

C → A: Loss of activity towards polyubiquitin. Ref.12 Ref.17

Sequence conflict

559

1

T → A in AAG28973. Ref.9

Sequence conflict

747

1

S → F in AAI25124. Ref.7

Sequence conflict

968

1

N → H in AAG28973. Ref.9

Secondary structure

1

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981

Helix Strand Turn

Details...

Beta strand

4 – 6

3

Helix

9 – 19

11

Beta strand

29 – 34

6

Helix

35 – 45

11

Turn

46 – 48

3

Turn

53 – 56

4

Helix

58 – 60

3

Helix

68 – 70

3

Beta strand

73 – 76

4

Turn

86 – 88

3

Beta strand

89 – 93

5

Helix

94 – 104

11

Beta strand

114 – 120

7

Beta strand

127 – 129

3

Beta strand

134 – 140

7

Beta strand

143 – 152

10

Helix

158 – 168

11

Beta strand

173 – 175

3

Beta strand

177 – 184

8

Beta strand

187 – 190

4

Helix

198 – 201

4

Beta strand

208 – 213

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 12, 2003. Version 3. Checksum: E81FEB9DE57F7089	FASTA	981	112,419
	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
	Isoform 2 [UniParc]. Checksum: 852ED3768FB5725A	FASTA	952	109,297
	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 PRGPSTPNVK NSNYCLPSYT 250 260 270 280 290 300 AYKNYDYSEP GRNNEQPGLC GLSNLGNTCF MNSAIQCLSN TPPLTEYFLN DKYQEELNFD 310 320 330 340 350 360 NPLGMRGEIA KSYAELIKQM WSGKFSYVTP RAFKTQVGRF APQFSGYQQQ DCQELLAFLL 370 380 390 400 410 420 DGLHEDLNRI RKKPYIQLKD ADGRPDKVVA EEAWENHLKR NDSIIVDIFH GLFKSTLVCP 430 440 450 460 470 480 ECAKISVTFD PFCYLTLPLP MKKERTLEVY LVRMDPLTKP MQYKVVVPKI GNILDLCTAL 490 500 510 520 530 540 SALSGIPADK MIVTDIYNHR FHRIFAMDEN LSSIMERDDI YVFEININRT EDTEHVIIPV 550 560 570 580 590 600 CLREKFRHSS YTHHTGSSLF GQPFLMAVPR NNTEDKLYNL LLLRMCRYVK ISTETEETEG 610 620 630 640 650 660 SLHCCKDQNI NGNGPNGIHE EGSPSEMETD EPDDESSQDQ ELPSENENSQ SEDSVGGDND 670 680 690 700 710 720 SENGLCTEDT CKGQLTGHKK RLFTFQFNNL GNTDINYIKD DTRHIRFDDR QLRLDERSFL 730 740 750 760 770 780 ALDWDPDLKK RYFDENAAED FEKHESVEYK PPKKPFVKLK DCIELFTTKE KLGAEDPWYC 790 800 810 820 830 840 PNCKEHQQAT KKLDLWSLPP VLVVHLKRFS YSRYMRDKLD TLVDFPINDL DMSEFLINPN 850 860 870 880 890 900 AGPCRYNLIA VSNHYGGMGG GHYTAFAKNK DDGKWYYFDD SSVSTASEDQ IVSKAAYVLF 910 920 930 940 950 YQRQDTFSGT GFFPLDRETK GASAATGIPL ESDEDSNDND NDIENENCMH TN
	Isoform 3 [UniParc]. Checksum: F9F83D3886404B11	FASTA	956	109,796
	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 IEQKNEQKNE DGTWPRGPST PNVKNSNYCL 250 260 270 280 290 300 PSYTAYKNYD YSEPGRNNEQ PGLCGLSNLG NTCFMNSAIQ CLSNTPPLTE YFLNDKYQEE 310 320 330 340 350 360 LNFDNPLGMR GEIAKSYAEL IKQMWSGKFS YVTPRAFKTQ VGRFAPQFSG YQQQDCQELL 370 380 390 400 410 420 AFLLDGLHED LNRIRKKPYI QLKDADGRPD KVVAEEAWEN HLKRNDSIIV DIFHGLFKST 430 440 450 460 470 480 LVCPECAKIS VTFDPFCYLT LPLPMKKERT LEVYLVRMDP LTKPMQYKVV VPKIGNILDL 490 500 510 520 530 540 CTALSALSGI PADKMIVTDI YNHRFHRIFA MDENLSSIME RDDIYVFEIN INRTEDTEHV 550 560 570 580 590 600 IIPVCLREKF RHSSYTHHTG SSLFGQPFLM AVPRNNTEDK LYNLLLLRMC RYVKISTETE 610 620 630 640 650 660 ETEGSLHCCK DQNINGNGPN GIHEEGSPSE METDEPDDES SQDQELPSEN ENSQSEDSVG 670 680 690 700 710 720 GDNDSENGLC TEDTCKGQLT GHKKRLFTFQ FNNLGNTDIN YIKDDTRHIR FDDRQLRLDE 730 740 750 760 770 780 RSFLALDWDP DLKKRYFDEN AAEDFEKHES VEYKPPKKPF VKLKDCIELF TTKEKLGAED 790 800 810 820 830 840 PWYCPNCKEH QQATKKLDLW SLPPVLVVHL KRFSYSRYMR DKLDTLVDFP INDLDMSEFL 850 860 870 880 890 900 INPNAGPCRY NLIAVSNHYG GMGGGHYTAF AKNKDDGKWY YFDDSSVSTA SEDQIVSKAA 910 920 930 940 950 YVLFYQRQDT FSGTGFFPLD RETKGASAAT GIPLESDEDS NDNDNDIENE NCMHTN
	Isoform 4 [UniParc]. Checksum: F69B0D2783E2A443	FASTA	235	27,094
	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 NKYMSNTFEP LNKPDSTIQD AGLYQGQVLV IEQKNEDGTW PRGPSTPKKP LEQSC

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[20]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[21]	"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].
[22]	"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.
[23]	"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, MASS SPECTROMETRY.
[24]	"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.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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.

IPI

IPI00000728.
IPI00219504.
IPI01015293.

RefSeq

NP_001239007.1. NM_001252078.1.
NP_001239008.1. NM_001252079.1.
NP_006304.1. NM_006313.2.

UniGene

Hs.434951.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W6V	NMR	-	A	1-120	[»]
3LMN	X-ray	2.15	A/B	1-133	[»]
3PPA	X-ray	2.35	A	6-223	[»]
3PV1	X-ray	2.60	A/B	1-223	[»]
3T9L	X-ray	1.50	A	1-222	[»]
4A3O	X-ray	2.20	A/B	6-223	[»]
4A3P	X-ray	1.40	A	6-223	[»]

ProteinModelPortal

Q9Y4E8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y4E8. 32 interactions.

STRING

9606.ENSP00000258123.

Protein family/group databases

MEROPS

C19.022.

PTM databases

PhosphoSite

Q9Y4E8.

Polymorphism databases

DMDM

28381406.

Proteomic databases

PaxDb

Q9Y4E8.

PRIDE

Q9Y4E8.

Protocols and materials databases

DNASU

9958.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000280377; ENSP00000280377; ENSG00000135655.
ENST00000312635; ENSP00000309240; ENSG00000135655.
ENST00000353364; ENSP00000258123; ENSG00000135655.

GeneID

9958.

KEGG

hsa:9958.

UCSC

uc001srb.2. human.
uc001src.2. human.

Organism-specific databases

CTD

9958.

GeneCards

GC12P062706.

H-InvDB

HIX0010773.

HGNC

HGNC:12613. USP15.

HPA

HPA006237.

MIM

604731. gene.

neXtProt

NX_Q9Y4E8.

PharmGKB

PA37239.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5560.

HOGENOM

HOG000264375.

HOVERGEN

HBG000864.

InParanoid

Q9Y4E8.

KO

K11835.

OMA

RMDPLAK.

OrthoDB

EOG4DNF3R.

PhylomeDB

Q9Y4E8.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q9Y4E8.

Bgee

Q9Y4E8.

CleanEx

HS_USP15.

Genevestigator

Q9Y4E8.

GermOnline

ENSG00000135655. Homo sapiens.

Family and domain databases

InterPro

IPR006615. Pept_C19_DUSP.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19.
IPR013792. RNA3'P_cycl/enolpyr_Trfase_a/b.
[Graphical view]

Pfam

PF06337. DUSP. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view]

SMART

SM00695. DUSP. 1 hit.
[Graphical view]

SUPFAM

SSF55205. RNA3'_cycl/enolpyr_transf_A/B. 1 hit.

PROSITE

PS51283. DUSP. 1 hit.
PS00972. UCH_2_1. 1 hit.
PS00973. UCH_2_2. 1 hit.
PS50235. UCH_2_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

USP15. human.

EvolutionaryTrace

Q9Y4E8.

GenomeRNAi

9958.

NextBio

37576.

SOURCE

Search...

Entry information

Entry name

UBP15_HUMAN

Accession

Primary (citable) accession number: Q9Y4E8
Secondary accession number(s): Q08AL5 , Q9H8G9, Q9HCA6, Q9UNP0, Q9Y5B5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	February 12, 2003
Last modified:	May 1, 2013
This is version 130 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.