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Protein

Ubiquitin carboxyl-terminal hydrolase 4

Gene

Usp4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:98905. Usp4.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Shuttles between the nucleus and cytoplasm. Exported to the cytoplasm in a CRM1-dependent manner and recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor.1 Publication

GO - Cellular componenti

Complete GO annotation...

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.
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.
MINTiMINT-4139272.
STRINGi10090.ENSMUSP00000035237.

Structurei

Secondary structure

1962
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi13 – 21Combined sources9
Turni22 – 25Combined sources4
Beta strandi33 – 38Combined sources6
Helixi39 – 49Combined sources11
Beta strandi51 – 53Combined sources3
Turni56 – 60Combined sources5
Helixi62 – 64Combined sources3
Helixi72 – 74Combined sources3
Beta strandi75 – 77Combined sources3
Turni78 – 81Combined sources4
Turni89 – 91Combined sources3
Beta strandi92 – 97Combined sources6
Helixi98 – 108Combined sources11
Beta strandi118 – 124Combined sources7
Beta strandi126 – 128Combined sources3
Beta strandi130 – 133Combined sources4
Beta strandi138 – 144Combined sources7
Beta strandi147 – 156Combined sources10
Helixi162 – 172Combined sources11
Beta strandi181 – 185Combined sources5
Beta strandi187 – 191Combined sources5
Turni202 – 206Combined sources5
Beta strandi211 – 217Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3JYUX-ray2.37A/B1-229[»]
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
Contains 1 DUSP domain.PROSITE-ProRule annotation
Contains 2 ubiquitin-like domains.Curated
Contains 1 USP domain.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1870. Eukaryota.
COG5560. LUCA.
GeneTreeiENSGT00670000097750.
HOGENOMiHOG000264375.
HOVERGENiHBG000864.
InParanoidiP35123.
KOiK11835.
OMAiAVCERIX.
OrthoDBiEOG091G0157.
TreeFamiTF106276.

Family and domain databases

Gene3Di3.30.2230.10. 1 hit.
InterProiIPR006615. Pept_C19_DUSP.
IPR001394. Peptidase_C19_UCH.
IPR028135. Ub_USP-typ.
IPR028134. USP4/12.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PANTHERiPTHR24006:SF360. PTHR24006:SF360. 2 hits.
PfamiPF06337. DUSP. 1 hit.
PF14836. Ubiquitin_3. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view]
SMARTiSM00695. DUSP. 1 hit.
[Graphical view]
SUPFAMiSSF143791. SSF143791. 1 hit.
PROSITEiPS51283. DUSP. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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.

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3JYUX-ray2.37A/B1-229[»]
ProteinModelPortaliP35123.
SMRiP35123.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204448. 1 interactor.
IntActiP35123. 1 interactor.
MINTiMINT-4139272.
STRINGi10090.ENSMUSP00000035237.

Protein family/group databases

MEROPSiC19.010.

PTM databases

iPTMnetiP35123.
PhosphoSitePlusiP35123.
SwissPalmiP35123.

Proteomic databases

EPDiP35123.
MaxQBiP35123.
PaxDbiP35123.
PeptideAtlasiP35123.
PRIDEiP35123.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7375.
MGIiMGI:98905. Usp4.

Phylogenomic databases

eggNOGiKOG1870. Eukaryota.
COG5560. LUCA.
GeneTreeiENSGT00670000097750.
HOGENOMiHOG000264375.
HOVERGENiHBG000864.
InParanoidiP35123.
KOiK11835.
OMAiAVCERIX.
OrthoDBiEOG091G0157.
TreeFamiTF106276.

Enzyme and pathway databases

ReactomeiR-MMU-5689880. Ub-specific processing proteases.

Miscellaneous databases

EvolutionaryTraceiP35123.
PROiP35123.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032612.
CleanExiMM_USP4.
ExpressionAtlasiP35123. baseline and differential.
GenevisibleiP35123. MM.

Family and domain databases

Gene3Di3.30.2230.10. 1 hit.
InterProiIPR006615. Pept_C19_DUSP.
IPR001394. Peptidase_C19_UCH.
IPR028135. Ub_USP-typ.
IPR028134. USP4/12.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PANTHERiPTHR24006:SF360. PTHR24006:SF360. 2 hits.
PfamiPF06337. DUSP. 1 hit.
PF14836. Ubiquitin_3. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view]
SMARTiSM00695. DUSP. 1 hit.
[Graphical view]
SUPFAMiSSF143791. SSF143791. 1 hit.
PROSITEiPS51283. DUSP. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP4_MOUSE
AccessioniPrimary (citable) accession number: P35123
Secondary accession number(s): O54704, Q8BTL9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 142 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.