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Protein

Ubiquitin carboxyl-terminal hydrolase 4

Gene

Usp4

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

Functioni

Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3. This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP. May also play a role in the regulation of quality control in the ER.By similarity

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).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei311NucleophilePROSITE-ProRule annotation1
Metal bindingi461ZincBy similarity1
Metal bindingi464ZincBy similarity1
Metal bindingi798ZincBy similarity1
Metal bindingi801ZincBy similarity1
Active sitei880Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-5357786 TNFR1-induced proapoptotic signaling
R-MMU-5357905 Regulation of TNFR1 signaling
R-MMU-5357956 TNFR1-induced NFkappaB signaling pathway
R-MMU-5689880 Ub-specific processing proteases

Protein family/group databases

MEROPSiC19.010

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 4 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 4
Ubiquitin thioesterase 4
Ubiquitin-specific-processing protease 4
Ubiquitous nuclear protein
Gene namesi
Name:Usp4
Synonyms:Unp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:98905 Usp4

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

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi461C → Q: Reduces the interaction with RB1. 1 Publication1
Mutagenesisi770 – 771KK → NS: Reduces nuclear localization. 1 Publication2

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806221 – 962Ubiquitin carboxyl-terminal hydrolase 4Add BLAST962

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei655PhosphoserineBy similarity1
Modified residuei675PhosphoserineCombined sources1
Modified residuei680PhosphoserineCombined sources1

Post-translational modificationi

Monoubiquitinated by TRIM21. Ubiquitination does not lead to its proteasomal degradation. Autodeubiquitinated (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP35123
MaxQBiP35123
PaxDbiP35123
PeptideAtlasiP35123
PRIDEiP35123

PTM databases

iPTMnetiP35123
PhosphoSitePlusiP35123
SwissPalmiP35123

Expressioni

Tissue specificityi

Expressed in brain, kidney, liver and spleen (at protein level).1 Publication

Developmental stagei

Overexpression leads to oncogenic transformation of NIH 3T3 cells.

Gene expression databases

BgeeiENSMUSG00000032612 Expressed in 296 organ(s), highest expression level in primary oocyte
CleanExiMM_USP4
ExpressionAtlasiP35123 baseline and differential
GenevisibleiP35123 MM

Interactioni

Subunit structurei

Interacts with RB1 (both dephosphorylated and hypophosphorylated forms). Interacts with RBL1 and RBL2. Interacts with ADORA2A (via cytoplasmic C-terminus); the interaction is direct. Interacts with SART3; recruits USP4 to its substrate PRPF3.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204448, 1 interactor
IntActiP35123, 1 interactor
MINTiP35123
STRINGi10090.ENSMUSP00000035237

Structurei

Secondary structure

1962
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP35123
SMRiP35123
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35123

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 122DUSPPROSITE-ProRule annotationAdd BLAST112
Domaini142 – 226Ubiquitin-like 1Add BLAST85
Domaini302 – 922USPAdd BLAST621
Domaini483 – 571Ubiquitin-like 2Add BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni27 – 216Necessary for interaction with SART3By similarityAdd BLAST190
Regioni405 – 407Necessary for interaction with RBL21 Publication3
Regioni459 – 463Necessary for interaction with RB1 and RBL21 Publication5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi133 – 141Nuclear export signal9
Motifi766 – 771Nuclear localization signal6

Domaini

The Ubiquitin-like domain 2 inserts into the catalytic domain and competes with the ubiquitin substrate, partially inhibiting DUB activity.By similarity

Sequence similaritiesi

Belongs to the peptidase C19 family. USP4 subfamily.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1870 Eukaryota
COG5560 LUCA
GeneTreeiENSGT00670000097750
HOGENOMiHOG000264375
HOVERGENiHBG000864
InParanoidiP35123
KOiK11835
OMAiHVSMLQP
OrthoDBiEOG091G0157
TreeFamiTF106276

Family and domain databases

InterProiView protein in InterPro
IPR035927 DUSP-like_sf
IPR038765 Papain_like_cys_pep_sf
IPR006615 Pept_C19_DUSP
IPR001394 Peptidase_C19_UCH
IPR028135 Ub_USP-typ
IPR028134 USP4
IPR018200 USP_CS
IPR028889 USP_dom
PANTHERiPTHR43913 PTHR43913, 1 hit
PfamiView protein in Pfam
PF06337 DUSP, 1 hit
PF14836 Ubiquitin_3, 1 hit
PF00443 UCH, 1 hit
SMARTiView protein in SMART
SM00695 DUSP, 1 hit
SUPFAMiSSF143791 SSF143791, 1 hit
SSF54001 SSF54001, 2 hits
PROSITEiView protein in PROSITE
PS51283 DUSP, 1 hit
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.iShow all

P35123-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAEGRGSRER PDVETQKTEL GALMGTTLQR GAQWYLIDSR WFKQWKKYVG
60 70 80 90 100
FDSWDMYNVG EHNLFPGPID NSGLFSDPES QTLKEHLIDE LDYVLVPAEA
110 120 130 140 150
WNKLLNWYGC VEGQQPIVRK VVEHGLFVKH CKVEVYLLEL KLCENSDPTN
160 170 180 190 200
VLSCHFSKAD TIATIEKEMR KLFNIPAERE TRLWNKYMSN TYEQLSKLDN
210 220 230 240 250
TIQDAGLYQG QVLVIEPQNE DGTWPRQSLQ SKSSTAPSRN FTTSSKPSAS
260 270 280 290 300
PYCSVSASLI ANGDSTNSSG MHSSGVSRGG SGFSASYNCQ EPPSPHIQPG
310 320 330 340 350
LCGLGNLGNT CFMNSALQCL SNTAPLTEYF LKDEYEAEIN RDNPLGMKGE
360 370 380 390 400
IAEAYAELIK QMWSGRDTHV APRMFKTQVG RFAPQFSGYQ QQDSQELLAF
410 420 430 440 450
ILDGLHEDLN RVKKKPYLEP KDANGRPDAV VAKEAWENHR LRNDSVIVDT
460 470 480 490 500
FHGLFKSTLV CPECAKVSVT FDPFCYLTLP LPLKKDRIME VFLVPADPQC
510 520 530 540 550
RPIQYRVTVP LMGAISDLCE ALSKLSGIAA ENMVVTDVYN HRFHKIFQMD
560 570 580 590 600
EGLSHITPRD DIFVYEVCNT SMDGSECITL PVYFREKKSR PSSASSGAVL
610 620 630 640 650
YGQPLLVSVP KHKLTLESLY QAVCDRISRY IKQPLPDEFL SSPLEPGACN
660 670 680 690 700
GSRSSYEGDE EEEMDHQEEG KEQLSEVEGS GEDDQGDDHS ESAQKVKGQP
710 720 730 740 750
RHKRLFTFSL VNSCGTADIN SLATDGKLLK LNSRSTLAID WDSETRSLYF
760 770 780 790 800
DEQESEACEK HLSMSQPQKK KKAAVALREC IELFTTMETL GEHDPWYCPT
810 820 830 840 850
CKKHQQATKK FDLWSLPKIL VVHLKRFSYN RYWRDKLDTV VEFPVRALNM
860 870 880 890 900
SEFVCDRSAR PYVYDLIAVS NHYGAMGVGH YTAYAKNRLN GKWYYFDDSS
910 920 930 940 950
VSLASEDQIV TKAAYVLFYQ RRDDECSSTS SLGSFPGSDG GVKLSSSHQG
960
MGDEEAYNMD TN
Length:962
Mass (Da):108,343
Last modified:July 27, 2011 - v3
Checksum:i95F95BE86186DA52
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A6YW28A0A0A6YW28_MOUSE
Ubiquitin carboxyl-terminal hydrola...
Usp4 mCG_13020
915Annotation score:
A0A0A6YVY7A0A0A6YVY7_MOUSE
Ubiquitin carboxyl-terminal hydrola...
Usp4
734Annotation score:
A0A0A6YW63A0A0A6YW63_MOUSE
Ubiquitin carboxyl-terminal hydrola...
Usp4
190Annotation score:
A0A0A6YWM7A0A0A6YWM7_MOUSE
Ubiquitin carboxyl-terminal hydrola...
Usp4
394Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti123 – 124EH → DD in AAB82339 (PubMed:8336951).Curated2
Sequence conflicti123 – 124EH → DD in AAC53587 (PubMed:9602026).Curated2
Sequence conflicti292P → A in AAB82339 (PubMed:8336951).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L00681 mRNA Translation: AAB82339.1
AF026469 Genomic DNA Translation: AAC53587.1
AK089425 mRNA Translation: BAC40877.1
AK143582 mRNA Translation: BAE25450.1
AK149964 mRNA Translation: BAE29198.1
AK169933 mRNA Translation: BAE41468.1
AK171271 mRNA Translation: BAE42357.1
CH466560 Genomic DNA Translation: EDL21282.1
CCDSiCCDS23523.1
PIRiI58376
RefSeqiNP_035808.2, NM_011678.2
UniGeneiMm.3974

Genome annotation databases

EnsembliENSMUST00000035237; ENSMUSP00000035237; ENSMUSG00000032612
GeneIDi22258
KEGGimmu:22258
UCSCiuc009rph.2 mouse

Similar proteinsi

Entry informationi

Entry nameiUBP4_MOUSE
AccessioniPrimary (citable) accession number: P35123
Secondary accession number(s): O54704, Q8BTL9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: July 27, 2011
Last modified: September 12, 2018
This is version 150 of the entry and version 3 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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