Q9R085 (UBP15_RAT) 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 carboxyl-terminal hydrolase of 109 kDa
Ubiquitin thioesterase 15
Ubiquitin-specific-processing protease 15

Gene names

Name:	Usp15
Synonyms:	ubp109

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	952 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. 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). Ref.1
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. Nucleus Ref.1.
Tissue specificity	Highly expressed in testis and spleen, and at lower level in other tissues. 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.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Molecular function	Hydrolase Protease Thiol protease
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB monoubiquitinated protein deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB pathway-restricted SMAD protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB transforming growth factor beta receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from direct assay Ref.1. Source: UniProtKB nucleus Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	cysteine-type endopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin thiolesterase activity Inferred from direct assay Ref.1. Source: UniProtKB ubiquitin-specific protease activity Inferred from direct assay Ref.1. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 952	951	Ubiquitin carboxyl-terminal hydrolase 15		PRO_0000420490
Regions
	Domain	7 – 118	112	DUSP
Sites
	Active site	269	1	Nucleophile By similarity
	Active site	862	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	932	1	Phosphoserine By similarity
	Modified residue	936	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9R085 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 6BE7449FD93CF658	FASTA	952	109,255
	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 PRGPSAPNVK 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 MKKERSLEVY LVRMDPLAKP MQYKVIVPKI GNILDLCTAL 490 500 510 520 530 540 SALSGVPADK MIVTDIYNHR FHRIFAMDEN LSSIMERDDI YVFEININRT EDTEHVVIPV 550 560 570 580 590 600 CLREKFRHSS YTHHTGSSLF GQPFLMAVPR NNTEDKLYNL LLLRMCRYVK MSTETEETDG 610 620 630 640 650 660 PLRCCEDQNI NGNGPNGIHE EGSPSEMETD EPDDESSQDQ ELPSENENSQ SEDSVGGDND 670 680 690 700 710 720 SENGLCTEET CKGRLTGHKK RLFTFQFNNL GNTDINYIKD DTRHIRFDDR QLRLDERSFL 730 740 750 760 770 780 ALDWDPDLKK RYFDENAAED FEKHESVEYK PPKRPFVKLK DCIELFTTKE KLGAEDPWYC 790 800 810 820 830 840 PNCKEHQQAT KKLDLWSLPP VLVVHLKRFS YSRYMRDKLD TLVDFPISDL DMSEFLINPN 850 860 870 880 890 900 AGPCRYNLIA VSNHYGGMGG GHYTAFAKNK DDGKWYYFDD SSVSSASEDQ IVSKAAYVLF 910 920 930 940 950 YQRQDTFSGT GFFPLDRETK GASAATGVPL ESDEDSNDND NDLENENCMH TN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Tissue-specificity, functional characterization and subcellular localization of a rat ubiquitin-specific processing protease, UBP109, whose mRNA expression is developmentally regulated." Park K.C., Choi E.J., Min S.W., Chung S.S., Kim H., Suzuki T., Tanaka K., Chung C.H. Biochem. J. 349:443-453(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Skeletal muscle.
[2]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF106657 mRNA. Translation: AAF14188.1.
IPI	IPI00205801.
RefSeq	NP_660185.1. NM_145184.1.
UniGene	Rn.161933.
3D structure databases
HSSP	HSSP built from PDB template 1NB8 based on UniProtKB Q93009.
ProteinModelPortal	Q9R085.
SMR	Q9R085. Positions 1-120.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000034485.
Protein family/group databases
MEROPS	C19.022.
PTM databases
PhosphoSite	Q9R085.
Proteomic databases
PRIDE	Q9R085.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	171329.
KEGG	rno:171329.
Organism-specific databases
CTD	9958.
RGD	628795. Usp15.
Phylogenomic databases
eggNOG	COG5560.
HOGENOM	HOG000264375.
HOVERGEN	HBG000864.
KO	K11835.
OrthoDB	EOG4DNF3R.
Gene expression databases
Genevestigator	Q9R085.
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
NextBio	35574809.

Entry information

Entry name

UBP15_RAT

Accession

Primary (citable) accession number: Q9R085
Secondary accession number(s): E9PSP9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2012
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program