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Protein

Ubiquitin carboxyl-terminal hydrolase 8

Gene

Usp8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity9 Publications

Catalytic activityi

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).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei748Nucleophile1
Active sitei1029Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processCell cycle, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-1358803 Downregulation of ERBB2:ERBB3 signaling
R-MMU-4641263 Regulation of FZD by ubiquitination
R-MMU-5689880 Ub-specific processing proteases
R-MMU-6807004 Negative regulation of MET activity

Protein family/group databases

MEROPSiC19.011

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 8 (EC:3.4.19.121 Publication)
Alternative name(s):
Deubiquitinating enzyme 8
Ubiquitin isopeptidase Y
Short name:
mUBPy
Ubiquitin thioesterase 8
Ubiquitin-specific-processing protease 8
Gene namesi
Name:Usp8
Synonyms:Kiaa0055, Ubpy
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1934029 Usp8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi405P → A: Abolishes interaction with the SH3 domain of STAM2. 1 Publication1
Mutagenesisi406Q → A: Does not affect interaction with the SH3 domain of STAM2. 1 Publication1
Mutagenesisi407V → A: Reduces interaction with the SH3 domain of STAM2. 1 Publication1
Mutagenesisi408D → A: Reduces interaction with the SH3 domain of STAM2. 1 Publication1
Mutagenesisi409R → A: Abolishes interaction with the SH3 domain of STAM2. 1 Publication1
Mutagenesisi410T → A: Does not affect interaction with the SH3 domain of STAM2. 1 Publication1
Mutagenesisi411K → A: Does not affect interaction with the SH3 domain of STAM2. 1 Publication1
Mutagenesisi412K → A: Abolishes interaction with the SH3 domain of STAM2. 1 Publication1
Mutagenesisi413P → A: Abolishes interaction with the SH3 domain of STAM2. 1 Publication1
Mutagenesisi680S → A: Abolishes the interaction with YWHAE and leads to accumulation in the nucleus. 2 Publications1
Mutagenesisi748C → A: Impairs deubiquitination of EPS15, RNF128 and RNF41. 4 Publications1
Mutagenesisi907T → A: Reduces stabilization activity on RNF41. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806281 – 1080Ubiquitin carboxyl-terminal hydrolase 8Add BLAST1080

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei160PhosphoserineBy similarity1
Modified residuei392PhosphoserineBy similarity1
Modified residuei446PhosphoserineBy similarity1
Modified residuei569PhosphothreonineBy similarity1
Modified residuei680Phosphoserine2 Publications1
Modified residuei681PhosphoserineBy similarity1
Modified residuei907Phosphothreonine1 Publication1

Post-translational modificationi

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.4 Publications
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.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ80U87
MaxQBiQ80U87
PaxDbiQ80U87
PRIDEiQ80U87

PTM databases

iPTMnetiQ80U87
PhosphoSitePlusiQ80U87

Expressioni

Tissue specificityi

Highly expressed in testis. Expressed at intermediate level in brain.2 Publications

Gene expression databases

BgeeiENSMUSG00000027363
CleanExiMM_USP8
ExpressionAtlasiQ80U87 baseline and differential
GenevisibleiQ80U87 MM

Interactioni

Subunit structurei

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.By similarity9 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi220000, 10 interactors
IntActiQ80U87, 7 interactors
MINTiQ80U87
STRINGi10090.ENSMUSP00000106046

Structurei

Secondary structure

11080
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi704 – 706Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UJ0X-ray1.70B699-709[»]
ProteinModelPortaliQ80U87
SMRiQ80U87
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 116MITAdd BLAST84
Domaini195 – 313RhodanesePROSITE-ProRule annotationAdd BLAST119
Domaini739 – 1071USPAdd BLAST333

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi405 – 413SH3-binding9

Domaini

The MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation.By similarity
The rhodanese domain is sufficient for RNF41-binding.

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG1868 Eukaryota
ENOG410XP8T LUCA
GeneTreeiENSGT00860000133682
HOGENOMiHOG000231497
HOVERGENiHBG012631
InParanoidiQ80U87
KOiK11839

Family and domain databases

Gene3Di3.40.250.10, 1 hit
InterProiView protein in InterPro
IPR001394 Peptidase_C19_UCH
IPR001763 Rhodanese-like_dom
IPR036873 Rhodanese-like_dom_sf
IPR015063 USP8_dimer
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00581 Rhodanese, 1 hit
PF00443 UCH, 1 hit
PF08969 USP8_dimer, 1 hit
SMARTiView protein in SMART
SM00450 RHOD, 1 hit
SUPFAMiSSF52821 SSF52821, 1 hit
PROSITEiView protein in PROSITE
PS50206 RHODANESE_3, 1 hit
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequencei

Sequence statusi: Complete.

Q80U87-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPAVASVPKE LYLSSSLKDL NKKTEVKPEK TSTKNYIHSA QKIFKTAEEC
60 70 80 90 100
RLDRDEERAY VLYMKYVAVY NLIKKRPDFK QQQDYYLSIL GPANIKKAIE
110 120 130 140 150
EAERLSESLK LRYEEAEVRK QLEEKDRREE EQLQQQKRQE MGREDSGAAA
160 170 180 190 200
KRSVENLLDS KTKTQRINGE KSEGAAAAER GAITAKELYT MMMDKNTSLI
210 220 230 240 250
IMDARKIQDY QHSCILDSLS VPEEAISPGV TASWIEANLS DDSKDTWKKR
260 270 280 290 300
GSVDYVVLLD WFSSAKDLLL GTTLRSLKDA LFKWESKTVL RHEPLVLEGG
310 320 330 340 350
YENWLLCYPQ FTTNAKVTPP PRSRAEEVSV SLDFTYPSLE EPVPSKLPTQ
360 370 380 390 400
MPPPPIETNE KALLVTDQDE KLRLSTQPAL AGPGAAPRAE ASPIIQPAPA
410 420 430 440 450
TKSVPQVDRT KKPSVKLPED HRIKSENTDQ SGRVLSDRST KPVFPSPTTM
460 470 480 490 500
LTDEEKARIH QETALLMEKN KQEKELWDKQ QKEQKEKLRR EEQERKAGKT
510 520 530 540 550
QDADERDSTE NQHKAKDGQE KKDSKQTKTE DRELSADGAQ EATGTQRQSK
560 570 580 590 600
SEHEASDAKV PVEGKRCPTS EAQKRPADVS PASVSGELNA GKAQREPLTR
610 620 630 640 650
ARSEEMGRIV PGLPLGWAKF LDPITGTFRY YHSPTNTVHM YPPEMAPSSA
660 670 680 690 700
PPSTPPTHKV KPQVPAERDR EPSKLKRSYS SPDITQALQE EEKRRPAVTP
710 720 730 740 750
MVNRENKPPC YPKAEISRLS ASQIRNLNPV FGGSGPALTG LRNLGNTCYM
760 770 780 790 800
NSILQCLCNA PHLADYFNRN CYQDDINRSN LLGHKGEVAE EFGIIMKALW
810 820 830 840 850
TGQYRYISPK DFKVTIGKIN DQFAGSSQQD SQELLLFLMD GLHEDLNKAD
860 870 880 890 900
NRKRHKEENN EHLDDLQAAE HAWQKHKQLN ESIIVALFQG QFKSTVQCLT
910 920 930 940 950
CRRRSRTFEA FMYLSLPLAS TSKCTLQDCL RLFSKEEKLT DNNRFYCSHC
960 970 980 990 1000
RARRDSLKKI EIWKLPPVLL VHLKRFSYDG RWKQKLQTSV DFPLENLDLS
1010 1020 1030 1040 1050
QYVIGPKNSL KKYNLFSVSN HYGGLDGGHY TAYCKNAARQ RWFKFDDHEV
1060 1070 1080
SDISVSSVRS SAAYILFYTS LGPRITDVAT
Length:1,080
Mass (Da):122,611
Last modified:March 1, 2004 - v2
Checksum:i7F458E3B1AF0B7FA
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti139Q → P in AAD38869 (PubMed:11500497).Curated1
Sequence conflicti151K → R in BAB18534 (PubMed:10982817).Curated1
Sequence conflicti349T → A in BAB18534 (PubMed:10982817).Curated1
Sequence conflicti370E → G in BAB18534 (PubMed:10982817).Curated1
Sequence conflicti557D → N in BAB18534 (PubMed:10982817).Curated1
Sequence conflicti576P → L in BAB18534 (PubMed:10982817).Curated1
Sequence conflicti837F → S in BAB18534 (PubMed:10982817).Curated1
Sequence conflicti865 – 873DLQAAEHAW → EPAGGRARL in BAB18534 (PubMed:10982817).Curated9
Sequence conflicti885 – 886VA → RL in BAB18534 (PubMed:10982817).Curated2
Sequence conflicti894S → A in BAB18534 (PubMed:10982817).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB045709 mRNA Translation: BAB18534.1
AF057146 mRNA Translation: AAD38869.1
AK122195 mRNA Translation: BAC65477.1 Different initiation.
AL732330 Genomic DNA No translation available.
BC027052 mRNA Translation: AAH27052.1
BC050947 mRNA Translation: AAH50947.1
BC061465 mRNA Translation: AAH61465.1
BC066126 mRNA Translation: AAH66126.1
CCDSiCCDS16687.1
RefSeqiNP_062703.2, NM_019729.3
UniGeneiMm.272629
Mm.490069

Genome annotation databases

EnsembliENSMUST00000028841; ENSMUSP00000028841; ENSMUSG00000027363
GeneIDi84092
KEGGimmu:84092
UCSCiuc008meb.2 mouse

Similar proteinsi

Entry informationi

Entry nameiUBP8_MOUSE
AccessioniPrimary (citable) accession number: Q80U87
Secondary accession number(s): A2AI53
, Q80YP2, Q8R0D3, Q9EQU1, Q9WVP5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: May 23, 2018
This is version 140 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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