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Q80U87 (UBP8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1080 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Contains 1 USP domain.

Sequence caution

The sequence BAC65477.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10801080Ubiquitin carboxyl-terminal hydrolase 8
PRO_0000080628

Regions

Domain33 – 11684MIT
Domain195 – 313119Rhodanese
Domain739 – 1071333USP
Motif405 – 4139SH3-binding

Sites

Active site7481Nucleophile
Active site10291Proton acceptor By similarity

Amino acid modifications

Modified residue1601Phosphoserine By similarity
Modified residue4461Phosphoserine By similarity
Modified residue5691Phosphothreonine By similarity
Modified residue6801Phosphoserine Ref.12 Ref.13
Modified residue6811Phosphoserine By similarity
Modified residue9071Phosphothreonine Ref.14

Experimental info

Mutagenesis4051P → A: Abolishes interaction with the SH3 domain of STAM2. Ref.1
Mutagenesis4061Q → A: Does not affect interaction with the SH3 domain of STAM2. Ref.1
Mutagenesis4071V → A: Reduces interaction with the SH3 domain of STAM2. Ref.1
Mutagenesis4081D → A: Reduces interaction with the SH3 domain of STAM2. Ref.1
Mutagenesis4091R → A: Abolishes interaction with the SH3 domain of STAM2. Ref.1
Mutagenesis4101T → A: Does not affect interaction with the SH3 domain of STAM2. Ref.1
Mutagenesis4111K → A: Does not affect interaction with the SH3 domain of STAM2. Ref.1
Mutagenesis4121K → A: Abolishes interaction with the SH3 domain of STAM2. Ref.1
Mutagenesis4131P → A: Abolishes interaction with the SH3 domain of STAM2. Ref.1
Mutagenesis6801S → A: Abolishes the interaction with YWHAE and leads to accumulation in the nucleus. Ref.12 Ref.13
Mutagenesis7481C → A: Impairs deubiquitination of EPS15, RNF128 and RNF41. Ref.6 Ref.7 Ref.9 Ref.10
Mutagenesis9071T → A: Reduces stabilization activity on RNF41. Ref.14
Sequence conflict1391Q → P in AAD38869. Ref.2
Sequence conflict1511K → R in BAB18534. Ref.1
Sequence conflict3491T → A in BAB18534. Ref.1
Sequence conflict3701E → G in BAB18534. Ref.1
Sequence conflict5571D → N in BAB18534. Ref.1
Sequence conflict5761P → L in BAB18534. Ref.1
Sequence conflict8371F → S in BAB18534. Ref.1
Sequence conflict865 – 8739DLQAAEHAW → EPAGGRARL in BAB18534. Ref.1
Sequence conflict885 – 8862VA → RL in BAB18534. Ref.1
Sequence conflict8941S → A in BAB18534. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q80U87 [UniParc].

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

FASTA1,080122,611
        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' 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. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., 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]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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.
RefSeqNP_062703.2. NM_019729.3.
UniGeneMm.272629.
Mm.490069.

3D structure databases

ProteinModelPortalQ80U87.
SMRQ80U87. Positions 6-132, 181-316, 718-1072.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid220000. 11 interactions.
IntActQ80U87. 7 interactions.
MINTMINT-144852.

Protein family/group databases

MEROPSC19.011.

PTM databases

PhosphoSiteQ80U87.

Proteomic databases

PaxDbQ80U87.
PRIDEQ80U87.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000028841; ENSMUSP00000028841; ENSMUSG00000027363.
GeneID84092.
KEGGmmu:84092.
UCSCuc008meb.2. mouse.

Organism-specific databases

CTD9101.
MGIMGI:1934029. Usp8.
RougeSearch...

Phylogenomic databases

eggNOGCOG5533.
GeneTreeENSGT00750000117363.
HOGENOMHOG000231497.
HOVERGENHBG012631.
KOK11839.
OrthoDBEOG7FR7GN.

Gene expression databases

ArrayExpressQ80U87.
BgeeQ80U87.
CleanExMM_USP8.
GenevestigatorQ80U87.

Family and domain databases

Gene3D3.40.250.10. 1 hit.
InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR001763. Rhodanese-like_dom.
IPR028889. UCH/PAN2.
IPR015063. USP8_dimer.
[Graphical view]
PfamPF00581. Rhodanese. 1 hit.
PF00443. UCH. 1 hit.
PF08969. USP8_dimer. 1 hit.
[Graphical view]
SMARTSM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMSSF52821. SSF52821. 1 hit.
PROSITEPS50206. RHODANESE_3. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio350878.
PROQ80U87.
SOURCESearch...

Entry information

Entry nameUBP8_MOUSE
AccessionPrimary (citable) accession number: Q80U87
Secondary accession number(s): A2AI53 expand/collapse secondary AC list , Q80YP2, Q8R0D3, Q9EQU1, Q9WVP5
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: April 16, 2014
This is version 103 of the entry and version 2 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