Ubiquitin carboxyl-terminal hydrolase 8

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Q80U87 (UBP8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 95. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase 8
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme 8
Ubiquitin isopeptidase Y
Short name=mUBPy
Ubiquitin thioesterase 8
Ubiquitin-specific-processing protease 8

Gene names

Name:	Usp8
Synonyms:	Kiaa0055, Ubpy

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1080 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controles tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1 By similarity. Ref.2 Ref.6 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.17
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	Forms a ternary complex with RNF128 and OTUB1. Interacts (via C-terminal UCH catalytic domain) with OTUB1 isoform 1. Interacts with STAM2 (via SH3 domain). Interacts with DNAJB3, EGFR, EPS15, RASGRF1, RNF41, YWHAE, YWHAG and YWHAZ. Interacts with NBR1, RASGRF1, RNF41 and IST1 By similarity. Associates with the ESCRT-0 complex and with microtubules. Interacts with BIRC6/bruce and KIF23/MKLP1. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13
Subcellular location	Cytoplasm. Nucleus. Endosome membrane; Peripheral membrane protein By similarity. Cell membrane; Peripheral membrane protein By similarity Ref.9 Ref.12 Ref.13.
Tissue specificity	Highly expressed in testis. Expressed at intermediate level in brain. Ref.2 Ref.8
Domain	The MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation By similarity. The rhodanese domain is sufficent for RNF41-binding.
Post-translational modification	Phosphorylation of Ser-680 is essential for interaction with YWHAE and for cytosol localization. Undergoes dephosphorylation at Ser-680 in the M phase. Tyrosine-phosphorylated in its N-terminal half in an EGFR-dependent manner. Ref.11 Ref.12 Ref.13 Ref.14 Ubiquitinated. Inactive form is mostly monoubiquitinated, but polyubiquitination happens too. Ubiquitination is increased in EGF-stimulated cells. Ubiquitination of active form is undetectable, suggesting a possibility that USP8 deubiquitinates itself, thereby regulating its own function. Ref.9
Sequence similarities	Belongs to the peptidase C19 family. Contains 1 MIT domain. Contains 1 rhodanese domain.
Sequence caution	The sequence BAC65477.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Cell cycle Ubl conjugation pathway
Cellular component	Cell membrane Cytoplasm Endosome Membrane Nucleus
Domain	SH3-binding
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Inferred from physical interaction Ref.2. Source: MGI cell cycle Inferred from electronic annotation. Source: UniProtKB-KW endosome organization Inferred from mutant phenotype Ref.10. Source: UniProtKB protein deubiquitination Inferred from direct assay Ref.9 Ref.10. Source: UniProtKB ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytosol Inferred from direct assay Ref.9. Source: UniProtKB extrinsic to endosome membrane Inferred from direct assay Ref.9. Source: UniProtKB midbody Inferred from direct assay PubMed 18388320. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro ubiquitin-specific protease activity Inferred from direct assay Ref.9 Ref.10. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1080

1080

Ubiquitin carboxyl-terminal hydrolase 8

PRO_0000080628

Regions

Domain

33 – 116

MIT

Domain

195 – 313

119

Rhodanese

Motif

405 – 413

SH3-binding

Sites

Active site

748

Nucleophile

Active site

1029

Proton acceptor By similarity

Amino acid modifications

Modified residue

160

Phosphoserine By similarity

Modified residue

446

Phosphoserine By similarity

Modified residue

569

Phosphothreonine By similarity

Modified residue

680

Phosphoserine Ref.12 Ref.13 Ref.16

Modified residue

681

Phosphoserine By similarity

Modified residue

907

Phosphothreonine Ref.14

Experimental info

Mutagenesis

405

P → A: Abolishes interaction with the SH3 domain of STAM2. Ref.1

Mutagenesis

406

Q → A: Does not affect interaction with the SH3 domain of STAM2. Ref.1

Mutagenesis

407

V → A: Reduces interaction with the SH3 domain of STAM2. Ref.1

Mutagenesis

408

D → A: Reduces interaction with the SH3 domain of STAM2. Ref.1

Mutagenesis

409

R → A: Abolishes interaction with the SH3 domain of STAM2. Ref.1

Mutagenesis

410

T → A: Does not affect interaction with the SH3 domain of STAM2. Ref.1

Mutagenesis

411

K → A: Does not affect interaction with the SH3 domain of STAM2. Ref.1

Mutagenesis

412

K → A: Abolishes interaction with the SH3 domain of STAM2. Ref.1

Mutagenesis

413

P → A: Abolishes interaction with the SH3 domain of STAM2. Ref.1

Mutagenesis

680

S → A: Abolishes the interaction with YWHAE and leads to accumulation in the nucleus. Ref.12 Ref.13

Mutagenesis

748

C → A: Impairs deubiquitination of EPS15, RNF128 and RNF41. Ref.6 Ref.7 Ref.9 Ref.10

Mutagenesis

907

T → A: Reduces stabilization activity on RNF41. Ref.14

Sequence conflict

139

Q → P in AAD38869. Ref.2

Sequence conflict

151

K → R in BAB18534. Ref.1

Sequence conflict

349

T → A in BAB18534. Ref.1

Sequence conflict

370

E → G in BAB18534. Ref.1

Sequence conflict

557

D → N in BAB18534. Ref.1

Sequence conflict

576

P → L in BAB18534. Ref.1

Sequence conflict

837

F → S in BAB18534. Ref.1

Sequence conflict

865 – 873

DLQAAEHAW → EPAGGRARL in BAB18534. Ref.1

Sequence conflict

885 – 886

VA → RL in BAB18534. Ref.1

Sequence conflict

894

S → A in BAB18534. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

Q80U87 [UniParc].

Last modified March 1, 2004. Version 2.
Checksum: 7F458E3B1AF0B7FA
Show »

FASTA

1,080

122,611

        10         20         30         40         50         60 
MPAVASVPKE LYLSSSLKDL NKKTEVKPEK TSTKNYIHSA QKIFKTAEEC RLDRDEERAY 

        70         80         90        100        110        120 
VLYMKYVAVY NLIKKRPDFK QQQDYYLSIL GPANIKKAIE EAERLSESLK LRYEEAEVRK 

       130        140        150        160        170        180 
QLEEKDRREE EQLQQQKRQE MGREDSGAAA KRSVENLLDS KTKTQRINGE KSEGAAAAER 

       190        200        210        220        230        240 
GAITAKELYT MMMDKNTSLI IMDARKIQDY QHSCILDSLS VPEEAISPGV TASWIEANLS 

       250        260        270        280        290        300 
DDSKDTWKKR GSVDYVVLLD WFSSAKDLLL GTTLRSLKDA LFKWESKTVL RHEPLVLEGG 

       310        320        330        340        350        360 
YENWLLCYPQ FTTNAKVTPP PRSRAEEVSV SLDFTYPSLE EPVPSKLPTQ MPPPPIETNE 

       370        380        390        400        410        420 
KALLVTDQDE KLRLSTQPAL AGPGAAPRAE ASPIIQPAPA TKSVPQVDRT KKPSVKLPED 

       430        440        450        460        470        480 
HRIKSENTDQ SGRVLSDRST KPVFPSPTTM LTDEEKARIH QETALLMEKN KQEKELWDKQ 

       490        500        510        520        530        540 
QKEQKEKLRR EEQERKAGKT QDADERDSTE NQHKAKDGQE KKDSKQTKTE DRELSADGAQ 

       550        560        570        580        590        600 
EATGTQRQSK SEHEASDAKV PVEGKRCPTS EAQKRPADVS PASVSGELNA GKAQREPLTR 

       610        620        630        640        650        660 
ARSEEMGRIV PGLPLGWAKF LDPITGTFRY YHSPTNTVHM YPPEMAPSSA PPSTPPTHKV 

       670        680        690        700        710        720 
KPQVPAERDR EPSKLKRSYS SPDITQALQE EEKRRPAVTP MVNRENKPPC YPKAEISRLS 

       730        740        750        760        770        780 
ASQIRNLNPV FGGSGPALTG LRNLGNTCYM NSILQCLCNA PHLADYFNRN CYQDDINRSN 

       790        800        810        820        830        840 
LLGHKGEVAE EFGIIMKALW TGQYRYISPK DFKVTIGKIN DQFAGSSQQD SQELLLFLMD 

       850        860        870        880        890        900 
GLHEDLNKAD NRKRHKEENN EHLDDLQAAE HAWQKHKQLN ESIIVALFQG QFKSTVQCLT 

       910        920        930        940        950        960 
CRRRSRTFEA FMYLSLPLAS TSKCTLQDCL RLFSKEEKLT DNNRFYCSHC RARRDSLKKI 

       970        980        990       1000       1010       1020 
EIWKLPPVLL VHLKRFSYDG RWKQKLQTSV DFPLENLDLS QYVIGPKNSL KKYNLFSVSN 

      1030       1040       1050       1060       1070       1080 
HYGGLDGGHY TAYCKNAARQ RWFKFDDHEV SDISVSSVRS SAAYILFYTS LGPRITDVAT

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP." Kato M., Miyazawa K., Kitamura N. J. Biol. Chem. 275:37481-37487(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SH3-BINDING, INTERACTION WITH STAM2, MUTAGENESIS OF PRO-405; GLN-406; VAL-407; ASP-408; ARG-409; THR-410; LYS-411; LYS-412 AND PRO-413.
[2]	"Cloning and characterization of mouse UBPy, a deubiquitinating enzyme that interacts with the ras guanine nucleotide exchange factor CDC25(Mm)/Ras-GRF1." Gnesutta N., Ceriani M., Innocenti M., Mauri I., Zippel R., Sturani E., Borgonovo B., Berruti G., Martegani E. J. Biol. Chem. 276:39448-39454(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH RASGRF1. Tissue: Embryo.
[3]	"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]. Tissue: Brain.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[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]. Strain: C57BL/6. Tissue: Brain and Kidney.
[6]	"Stabilization of the E3 ubiquitin ligase Nrdp1 by the deubiquitinating enzyme USP8." Wu X., Yen L., Irwin L., Sweeney C., Carraway K.L. III Mol. Cell. Biol. 24:7748-7757(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH RNF41, FUNCTION, MUTAGENESIS OF CYS-748.
[7]	"Two isoforms of otubain 1 regulate T cell anergy via GRAIL." Soares L., Seroogy C., Skrenta H., Anandasabapathy N., Lovelace P., Chung C.D., Engleman E., Fathman C.G. Nat. Immunol. 5:45-54(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH OTUB1 AND RNF128, MUTAGENESIS OF CYS-748.
[8]	"The deubiquitinating enzyme mUBPy interacts with the sperm-specific molecular chaperone MSJ-1: the relation with the proteasome, acrosome, and centrosome in mouse male germ cells." Berruti G., Martegani E. Biol. Reprod. 72:14-21(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INTERACTION WITH DNAJB3.
[9]	"Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes." Mizuno E., Iura T., Mukai A., Yoshimori T., Kitamura N., Komada M. Mol. Biol. Cell 16:5163-5174(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, MUTAGENESIS OF CYS-748.
[10]	"A deubiquitinating enzyme UBPY regulates the level of protein ubiquitination on endosomes." Mizuno E., Kobayashi K., Yamamoto A., Kitamura N., Komada M. Traffic 7:1017-1031(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-748, INTERACTION WITH ESP15.
[11]	"UBPY-mediated epidermal growth factor receptor (EGFR) de-ubiquitination promotes EGFR degradation." Alwan H.A., van Leeuwen J.E. J. Biol. Chem. 282:1658-1669(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH EGFR, FUNCTION.
[12]	"Identification of 14-3-3epsilon substrates from embryonic murine brain." Ballif B.A., Cao Z., Schwartz D., Carraway K.L. III, Gygi S.P. J. Proteome Res. 5:2372-2379(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-680, INTERACTION WITH YWHAE, MUTAGENESIS OF SER-680, SUBCELLULAR LOCATION.
[13]	"14-3-3-dependent inhibition of the deubiquitinating activity of UBPY and its cancellation in the M phase." Mizuno E., Kitamura N., Komada M. Exp. Cell Res. 313:3624-3634(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-680, INTERACTION WITH YWHAE; YWHAG AND YWHAZ, MUTAGENESIS OF SER-680, SUBCELLULAR LOCATION.
[14]	"Neuregulin-induced ErbB3 downregulation is mediated by a protein stability cascade involving the E3 ubiquitin ligase Nrdp1." Cao Z., Wu X., Yen L., Sweeney C., Carraway K.L. III Mol. Cell. Biol. 27:2180-2188(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT THR-907, MUTAGENESIS OF THR-907.
[15]	"Essential role of ubiquitin-specific protease 8 for receptor tyrosine kinase stability and endocytic trafficking in vivo." Niendorf S., Oksche A., Kisser A., Lohler J., Prinz M., Schorle H., Feller S., Lewitzky M., Horak I., Knobeloch K.P. Mol. Cell. Biol. 27:5029-5039(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-680, MASS SPECTROMETRY. Tissue: Melanoma.
[17]	"USP8, a regulator of endosomal sorting, is involved in mouse acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules." Berruti G., Ripolone M., Ceriani M. Biol. Reprod. 82:930-939(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ASSOCIATION WITH THE ESCRT-0 COMPLEX, MICROTUBULE-BINDING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB045709 mRNA. Translation: BAB18534.1. AF057146 mRNA. Translation: AAD38869.1. AK122195 mRNA. Translation: BAC65477.1. Different initiation. AL732330 Genomic DNA. Translation: CAM14544.1. BC027052 mRNA. Translation: AAH27052.1. BC050947 mRNA. Translation: AAH50947.1. BC061465 mRNA. Translation: AAH61465.1. BC066126 mRNA. Translation: AAH66126.1.
IPI	IPI00171977.
RefSeq	NP_062703.2. NM_019729.3.
UniGene	Mm.272629. Mm.490069.
3D structure databases
ProteinModelPortal	Q80U87.
SMR	Q80U87. Positions 6-132, 181-316, 718-1072.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q80U87. 2 interactions.
MINT	MINT-144852.
Protein family/group databases
MEROPS	C19.011.
PTM databases
PhosphoSite	Q80U87.
Proteomic databases
PaxDb	Q80U87.
PRIDE	Q80U87.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000028841; ENSMUSP00000028841; ENSMUSG00000027363.
GeneID	84092.
KEGG	mmu:84092.
UCSC	uc008meb.1. mouse.
Organism-specific databases
CTD	9101.
MGI	MGI:1934029. Usp8.
Rouge	Search...
Phylogenomic databases
eggNOG	COG5533.
GeneTree	ENSGT00670000097591.
HOGENOM	HOG000231497.
HOVERGEN	HBG012631.
KO	K11839.
OrthoDB	EOG4XKV6B.
Gene expression databases
ArrayExpress	Q80U87.
Bgee	Q80U87.
CleanEx	MM_USP8.
Genevestigator	Q80U87.
GermOnline	ENSMUSG00000027363. Mus musculus.
Family and domain databases
Gene3D	3.40.250.10. 1 hit.
InterPro	IPR015063. DUF1873. IPR018200. Pept_C19ubi-hydrolase_C_CS. IPR001394. Peptidase_C19. IPR001763. Rhodanese-like_dom. [Graphical view]
Pfam	PF08969. DUF1873. 1 hit. PF00581. Rhodanese. 1 hit. PF00443. UCH. 1 hit. [Graphical view]
SMART	SM00450. RHOD. 1 hit. [Graphical view]
SUPFAM	SSF52821. Rhodanese-like. 1 hit.
PROSITE	PS50206. RHODANESE_3. 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	350878.
SOURCE	Search...

Entry information

Entry name

UBP8_MOUSE

Accession

Primary (citable) accession number: Q80U87
Secondary accession number(s): A2AI53

Q9WVP5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	March 1, 2004
Last modified:	May 1, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents