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Protein

Ubiquitin carboxyl-terminal hydrolase 4

Gene

USP4

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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 bindingi799ZincBy similarity1
Metal bindingi802ZincBy similarity1
Active sitei881Proton 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-BTA-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
Gene namesi
Name:USP4
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 22

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • 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. The relative amounts found in the nucleus and cytoplasm vary according to the cell type.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003016681 – 963Ubiquitin carboxyl-terminal hydrolase 4Add BLAST963

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei675PhosphoserineBy similarity1
Modified residuei680PhosphoserineBy similarity1

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

PaxDbiA6QR55.
PRIDEiA6QR55.

Expressioni

Gene expression databases

BgeeiENSBTAG00000011899.

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 similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000015787.

Structurei

3D structure databases

ProteinModelPortaliA6QR55.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 122DUSPPROSITE-ProRule annotationAdd BLAST112
Domaini142 – 226Ubiquitin-like 1Add BLAST85
Domaini302 – 923USPAdd BLAST622
Domaini483 – 571Ubiquitin-like 2Add BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni27 – 216Necessary for interaction with SART3By similarityAdd BLAST190
Regioni405 – 407Necessary for interaction with RBL2By similarity3
Regioni459 – 463Necessary for interaction with RB1 and RBL2By similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi133 – 141Nuclear export signalBy similarity9
Motifi767 – 772Nuclear localization signalBy similarity6

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.
InParanoidiA6QR55.
KOiK11835.
OMAiMEIFLVP.
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.

A6QR55-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEGGGYRER PDAETQKSEL GALMRTTLQR GAQWYLIDSR WFKQWKKYVG
60 70 80 90 100
FDSWDMYNVG EHNLYPGPID 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
TVQDAGLYQG QVLVIEPQNE DGTWPRQTQQ SKSSTAPSRN FTTSPKSSAS
260 270 280 290 300
PYSSVSASPI ANGDSTNTSG MHSSGVSRGG SGFSASYNCQ ESPLTHVQPG
310 320 330 340 350
LCGLGNLGNT CFMNSALQCL SNTAPLTDYF LKDEYEAEIN RDNPLGMKGE
360 370 380 390 400
IAEAYAELIK QMWSGRDAHV APRMFKTQVG RFAPQFSGYQ QQDSQELLAF
410 420 430 440 450
LLDGLHEDLN RVKKKPYLEL KDANGRPDAV VAKEAWENHR LRNDSVIVDT
460 470 480 490 500
FHGLFKSTLV CPECAKVSVT FDPFCYLTLP LPLKKDRVME IFLVPADPRC
510 520 530 540 550
RPTQYRVVVP LMGAVSDLCE ALSKLSGIAA ENMVVTDVYN HRFHKIFQMD
560 570 580 590 600
EGLNHIMPRD DIFVYEVCST SPDGSECVTL PVYFRERKSR PSSTSTGAVL
610 620 630 640 650
YGQPLLVSVP KHKLTLESLY QAVCERISRY IKQPLPDESG SSPLELGACN
660 670 680 690 700
GSRSGCAGED EEEMEHQEEG REQLSETEGS GDDEPGSDHG EATQKKNKGR
710 720 730 740 750
PCPRRLFTFS LVNSYGTADI NSLATDGKLL KLNSRSTLAI DWDSETRSCY
760 770 780 790 800
YNEQESETYE KHVSMLQPQK KKKTAVALRD CIELFTTMET LGEHDPWYCP
810 820 830 840 850
NCKKHQQATK KFDLWSLPKI LVVHLKRFSY NRYWRDKLDT VVEFPVRGLN
860 870 880 890 900
MSEFVCDPSA RPYVYDLIAV SNHYGAMGVG HYTAYAKNKL NGKWYYFDDS
910 920 930 940 950
NVSLACEDQI VTKAAYVLFY QRRDDEFHKT PSLSFPGSSD GGARPSSSQQ
960
GTGDDETYSM DTN
Length:963
Mass (Da):108,510
Last modified:August 21, 2007 - v1
Checksum:i6D132FFE8C371A60
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC150120 mRNA. Translation: AAI50121.1.
RefSeqiNP_001093789.1. NM_001100319.1.
UniGeneiBt.52457.

Genome annotation databases

EnsembliENSBTAT00000015787; ENSBTAP00000015787; ENSBTAG00000011899.
GeneIDi508042.
KEGGibta:508042.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC150120 mRNA. Translation: AAI50121.1.
RefSeqiNP_001093789.1. NM_001100319.1.
UniGeneiBt.52457.

3D structure databases

ProteinModelPortaliA6QR55.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000015787.

Protein family/group databases

MEROPSiC19.010.

Proteomic databases

PaxDbiA6QR55.
PRIDEiA6QR55.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000015787; ENSBTAP00000015787; ENSBTAG00000011899.
GeneIDi508042.
KEGGibta:508042.

Organism-specific databases

CTDi7375.

Phylogenomic databases

eggNOGiKOG1870. Eukaryota.
COG5560. LUCA.
GeneTreeiENSGT00670000097750.
HOGENOMiHOG000264375.
HOVERGENiHBG000864.
InParanoidiA6QR55.
KOiK11835.
OMAiMEIFLVP.
OrthoDBiEOG091G0157.
TreeFamiTF106276.

Enzyme and pathway databases

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

Gene expression databases

BgeeiENSBTAG00000011899.

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_BOVIN
AccessioniPrimary (citable) accession number: A6QR55
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: August 21, 2007
Last modified: October 5, 2016
This is version 68 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. 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.