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P35123 (UBP4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Usp4
Synonyms:Unp
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length962 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Plays a role in the regulation of quality control in the ER By similarity.

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

Interacts with RB1 (both dephosphorylated and hypophosphorylated forms). Interacts with ADORA2A (via cytoplasmic C-terminus); the interaction is direct By similarity. Interacts with RB1, RBL1 and RBL2. Ref.5

Subcellular location

Cytoplasm. Nucleus. 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. Ref.6

Tissue specificity

Expressed in brain, kidney, liver and spleen (at protein level). Ref.6

Developmental stage

Overexpression leads to oncogenic transformation of NIH 3T3 cells.

Domain

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

Post-translational modification

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

Sequence similarities

Belongs to the peptidase C19 family. USP4 subfamily.

Contains 1 DUSP domain.

Contains 2 ubiquitin-like domains.

Contains 1 USP domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 962962Ubiquitin carboxyl-terminal hydrolase 4
PRO_0000080622

Regions

Domain11 – 122112DUSP
Domain142 – 22685Ubiquitin-like 1
Domain302 – 922621USP
Domain483 – 57189Ubiquitin-like 2
Region405 – 4073Necessary for interaction with RBL2
Region459 – 4635Necessary for interaction with RB1 and RBL2
Motif133 – 1419Nuclear export signal
Motif766 – 7716Nuclear localization signal

Sites

Active site3111Nucleophile By similarity
Active site8801Proton acceptor By similarity
Metal binding4611Zinc By similarity
Metal binding4641Zinc By similarity
Metal binding7981Zinc By similarity
Metal binding8011Zinc By similarity

Experimental info

Mutagenesis4611C → Q: Reduces the interaction with RB1. Ref.5
Mutagenesis770 – 7712KK → NS: Reduces nuclear localization. Ref.6
Sequence conflict123 – 1242EH → DD in AAB82339. Ref.1
Sequence conflict123 – 1242EH → DD in AAC53587. Ref.2
Sequence conflict2921P → A in AAB82339. Ref.1

Secondary structure

......................................... 962
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P35123 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 95F95BE86186DA52

FASTA962108,343
        10         20         30         40         50         60 
MAEGRGSRER PDVETQKTEL GALMGTTLQR GAQWYLIDSR WFKQWKKYVG FDSWDMYNVG 

        70         80         90        100        110        120 
EHNLFPGPID NSGLFSDPES QTLKEHLIDE LDYVLVPAEA WNKLLNWYGC VEGQQPIVRK 

       130        140        150        160        170        180 
VVEHGLFVKH CKVEVYLLEL KLCENSDPTN VLSCHFSKAD TIATIEKEMR KLFNIPAERE 

       190        200        210        220        230        240 
TRLWNKYMSN TYEQLSKLDN TIQDAGLYQG QVLVIEPQNE DGTWPRQSLQ SKSSTAPSRN 

       250        260        270        280        290        300 
FTTSSKPSAS PYCSVSASLI ANGDSTNSSG MHSSGVSRGG SGFSASYNCQ EPPSPHIQPG 

       310        320        330        340        350        360 
LCGLGNLGNT CFMNSALQCL SNTAPLTEYF LKDEYEAEIN RDNPLGMKGE IAEAYAELIK 

       370        380        390        400        410        420 
QMWSGRDTHV APRMFKTQVG RFAPQFSGYQ QQDSQELLAF ILDGLHEDLN RVKKKPYLEP 

       430        440        450        460        470        480 
KDANGRPDAV VAKEAWENHR LRNDSVIVDT FHGLFKSTLV CPECAKVSVT FDPFCYLTLP 

       490        500        510        520        530        540 
LPLKKDRIME VFLVPADPQC RPIQYRVTVP LMGAISDLCE ALSKLSGIAA ENMVVTDVYN 

       550        560        570        580        590        600 
HRFHKIFQMD EGLSHITPRD DIFVYEVCNT SMDGSECITL PVYFREKKSR PSSASSGAVL 

       610        620        630        640        650        660 
YGQPLLVSVP KHKLTLESLY QAVCDRISRY IKQPLPDEFL SSPLEPGACN GSRSSYEGDE 

       670        680        690        700        710        720 
EEEMDHQEEG KEQLSEVEGS GEDDQGDDHS ESAQKVKGQP RHKRLFTFSL VNSCGTADIN 

       730        740        750        760        770        780 
SLATDGKLLK LNSRSTLAID WDSETRSLYF DEQESEACEK HLSMSQPQKK KKAAVALREC 

       790        800        810        820        830        840 
IELFTTMETL GEHDPWYCPT CKKHQQATKK FDLWSLPKIL VVHLKRFSYN RYWRDKLDTV 

       850        860        870        880        890        900 
VEFPVRALNM SEFVCDRSAR PYVYDLIAVS NHYGAMGVGH YTAYAKNRLN GKWYYFDDSS 

       910        920        930        940        950        960 
VSLASEDQIV TKAAYVLFYQ RRDDECSSTS SLGSFPGSDG GVKLSSSHQG MGDEEAYNMD 


TN 

« Hide

References

« Hide 'large scale' references
[1]"Unp, a mouse gene related to the tre oncogene."
Gupta K., Copeland N.G., Gilbert D.J., Jenkins N.A., Gray D.A.
Oncogene 8:2307-2310(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA].
[2]"Genomic structure of Unp, a murine gene encoding a ubiquitin-specific protease."
di Fruscio M., Gilchrist C.A., Baker R.T., Gray D.A.
Biochim. Biophys. Acta 1398:9-17(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129.
Tissue: Testis.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Bone marrow and Spleen.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Association of UNP, a ubiquitin-specific protease, with the pocket proteins pRb, p107 and p130."
Blanchette P., Gilchrist C.A., Baker R.T., Gray D.A.
Oncogene 20:5533-5537(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RB1; RBL1 AND RBL2, MUTAGENESIS OF CYS-461.
[6]"Nuclear-cytoplasmic shuttling of the oncogenic mouse UNP/USP4 deubiquitylating enzyme."
Soboleva T.A., Jans D.A., Johnson-Saliba M., Baker R.T.
J. Biol. Chem. 280:745-752(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 770-GLN--LYS-771, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"Crystal structure of the N-terminal domains of the ubiquitin specific peptidase 4 (USP4)."
Structural genomics consortium (SGC)
Submitted (NOV-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.37 ANGSTROMS) OF 1-229.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRI58376.
RefSeqNP_035808.2. NM_011678.2.
UniGeneMm.3974.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3JYUX-ray2.37A/B1-229[»]
ProteinModelPortalP35123.
SMRP35123. Positions 7-226, 297-483, 775-924.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP35123. 1 interaction.
MINTMINT-4139272.

Protein family/group databases

MEROPSC19.010.

PTM databases

PhosphoSiteP35123.

Proteomic databases

PaxDbP35123.
PRIDEP35123.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000035237; ENSMUSP00000035237; ENSMUSG00000032612.
GeneID22258.
KEGGmmu:22258.
UCSCuc009rph.2. mouse.

Organism-specific databases

CTD7375.
MGIMGI:98905. Usp4.

Phylogenomic databases

eggNOGCOG5560.
GeneTreeENSGT00670000097750.
HOGENOMHOG000264375.
HOVERGENHBG000864.
InParanoidQ8BTL9.
KOK11835.
OMACERISRY.
OrthoDBEOG77Q4VW.
TreeFamTF106276.

Gene expression databases

ArrayExpressP35123.
BgeeP35123.
CleanExMM_USP4.
GenevestigatorP35123.

Family and domain databases

Gene3D3.30.2230.10. 1 hit.
InterProIPR006615. Pept_C19_DUSP.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028135. Ub_USP-typ.
IPR028889. UCH/PAN2.
IPR028134. USP.
[Graphical view]
PANTHERPTHR24006:SF34. PTHR24006:SF34. 1 hit.
PfamPF06337. DUSP. 1 hit.
PF14836. Ubiquitin_3. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view]
SMARTSM00695. DUSP. 1 hit.
[Graphical view]
SUPFAMSSF143791. SSF143791. 1 hit.
PROSITEPS51283. DUSP. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP35123.
NextBio302345.
PROP35123.
SOURCESearch...

Entry information

Entry nameUBP4_MOUSE
AccessionPrimary (citable) accession number: P35123
Secondary accession number(s): O54704, Q8BTL9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 118 of the entry and version 3 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot