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P54578 (UBP14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ubiquitin carboxyl-terminal hydrolase 14

EC=3.4.19.12
Alternative name(s):
Deubiquitinating enzyme 14
Ubiquitin thioesterase 14
Ubiquitin-specific-processing protease 14
Gene names
Name:USP14
Synonyms:TGT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length494 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs). Ref.8 Ref.10 Ref.11

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). Ref.17

Subunit structure

Homodimer Potential. Associates with the 26S proteasome. Interacts with FANCC, CXCR4 and ERN1. Ref.6 Ref.10 Ref.11

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein Ref.11.

Sequence similarities

Belongs to the peptidase C19 family. USP14/UBP6 subfamily.

Contains 1 ubiquitin-like domain.

Contains 1 USP domain.

Caution

Was originally (Ref.1) thought to be a guanine tRNA-ribosyltransferase.

Sequence caution

The sequence CR976282 differs from that shown. Reason: Frameshift at position 288.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentCell membrane
Cytoplasm
Membrane
Proteasome
   Coding sequence diversityAlternative splicing
   Molecular functionHydrolase
Protease
Thiol protease
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of endopeptidase activity

Inferred from mutant phenotype Ref.8. Source: GOC

protein deubiquitination

Inferred from direct assay PubMed 23958854. Source: FlyBase

regulation of chemotaxis

Inferred from mutant phenotype Ref.11. Source: UniProtKB

regulation of proteasomal protein catabolic process

Inferred from mutant phenotype Ref.8. Source: UniProtKB

synaptic transmission

Inferred from electronic annotation. Source: Ensembl

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcell surface

Inferred from direct assay Ref.11. Source: UniProtKB

cytoplasm

Inferred from direct assay. Source: HPA

cytoplasmic membrane-bounded vesicle

Inferred from direct assay Ref.11. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

proteasome complex

Inferred from electronic annotation. Source: UniProtKB-KW

synapse

Inferred from electronic annotation. Source: Ensembl

   Molecular_functioncysteine-type endopeptidase activity

Traceable author statement PubMed 9827704. Source: ProtInc

endopeptidase inhibitor activity

Inferred from mutant phenotype Ref.8. Source: UniProtKB

proteasome binding

Inferred from direct assay Ref.8. Source: UniProtKB

tRNA guanylyltransferase activity

Traceable author statement PubMed 8579355. Source: ProtInc

ubiquitin thiolesterase activity

Inferred from direct assay Ref.11. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from direct assay PubMed 23958854. Source: FlyBase

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PPP3CAQ082093EBI-1048016,EBI-352922

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P54578-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P54578-2)

The sequence of this isoform differs from the canonical sequence as follows:
     66-100: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 494494Ubiquitin carboxyl-terminal hydrolase 14
PRO_0000080636

Regions

Domain4 – 8077Ubiquitin-like
Domain105 – 483379USP

Sites

Active site1141Nucleophile Probable
Active site4351Proton acceptor By similarity

Amino acid modifications

Modified residue1431Phosphoserine Ref.7 Ref.12 Ref.14 Ref.16
Modified residue2351Phosphothreonine Ref.14
Modified residue4491N6-acetyllysine Ref.13

Natural variations

Alternative sequence66 – 10035Missing in isoform 2.
VSP_047343

Secondary structure

.............................................................. 494
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: E6D4679A86E9DF00

FASTA49456,069
        10         20         30         40         50         60 
MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG GTLKDDDWGN 

        70         80         90        100        110        120 
IKIKNGMTLL MMGSADALPE EPSAKTVFVE DMTEEQLASA MELPCGLTNL GNTCYMNATV 

       130        140        150        160        170        180 
QCIRSVPELK DALKRYAGAL RASGEMASAQ YITAALRDLF DSMDKTSSSI PPIILLQFLH 

       190        200        210        220        230        240 
MAFPQFAEKG EQGQYLQQDA NECWIQMMRV LQQKLEAIED DSVKETDSSS ASAATPSKKK 

       250        260        270        280        290        300 
SLIDQFFGVE FETTMKCTES EEEEVTKGKE NQLQLSCFIN QEVKYLFTGL KLRLQEEITK 

       310        320        330        340        350        360 
QSPTLQRNAL YIKSSKISRL PAYLTIQMVR FFYKEKESVN AKVLKDVKFP LMLDMYELCT 

       370        380        390        400        410        420 
PELQEKMVSF RSKFKDLEDK KVNQQPNTSD KKSSPQKEVK YEPFSFADDI GSNNCGYYDL 

       430        440        450        460        470        480 
QAVLTHQGRS SSSGHYVSWV KRKQDEWIKF DDDKVSIVTP EDILRLSGGG DWHIAYVLLY 

       490 
GPRRVEIMEE ESEQ 

« Hide

Isoform 2 [UniParc].

Checksum: 3EDE73254891B166
Show »

FASTA45952,386

References

« Hide 'large scale' references
[1]"tRNA-guanine transglycosylase cDNA from human placenta."
Deshpande K.L., Katze J.R.
Submitted (AUG-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Placenta.
[2]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Skin.
[5]Heil O., Ebert L., Hennig S., Henze S., Radelof U., Schneider D., Korn B.
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-308 (ISOFORM 2).
Tissue: T-cell.
[6]"Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport."
Reuter T.Y., Medhurst A.L., Waisfisz Q., Zhi Y., Herterich S., Hoehn H., Gross H.J., Joenje H., Hoatlin M.E., Mathew C.G., Huber P.A.
Exp. Cell Res. 289:211-221(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FANCC.
[7]"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment."
Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.
J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: T-cell.
[8]"Relative structural and functional roles of multiple deubiquitylating proteins associated with mammalian 26S proteasome."
Koulich E., Li X., DeMartino G.N.
Mol. Biol. Cell 19:1072-1082(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH THE 26S PROTEASOME, FUNCTION.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"USP14 inhibits ER-associated degradation via interaction with IRE1alpha."
Nagai A., Kadowaki H., Maruyama T., Takeda K., Nishitoh H., Ichijo H.
Biochem. Biophys. Res. Commun. 379:995-1000(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ERN1.
[11]"Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but not ERK activation."
Mines M.A., Goodwin J.S., Limbird L.E., Cui F.F., Fan G.H.
J. Biol. Chem. 284:5742-5752(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CXCR4, FUNCTION, SUBCELLULAR LOCATION.
[12]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[13]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-449, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143 AND THR-235, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14."
Hu M., Li P., Song L., Jeffrey P.D., Chenova T.A., Wilkinson K.D., Cohen R.E., Shi Y.
EMBO J. 24:3747-3756(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 91-494, CATALYTIC ACTIVITY, ACTIVE SITE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U30888 mRNA. Translation: AAB60365.1.
BT007183 mRNA. Translation: AAP35847.1.
AP000845 Genomic DNA. No translation available.
BC003556 mRNA. Translation: AAH03556.1.
CR976282 mRNA. No translation available.
PIRG01932.
RefSeqNP_001032411.1. NM_001037334.1.
NP_005142.1. NM_005151.3.
UniGeneHs.464416.
Hs.707058.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2AYNX-ray3.20A/B/C91-494[»]
2AYOX-ray3.50A91-494[»]
ProteinModelPortalP54578.
SMRP54578. Positions 6-86, 98-483.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114551. 53 interactions.
IntActP54578. 30 interactions.
MINTMINT-3020275.
STRING9606.ENSP00000261601.

Chemistry

ChEMBLCHEMBL1293295.

Protein family/group databases

MEROPSC19.015.

PTM databases

PhosphoSiteP54578.

Polymorphism databases

DMDM1729927.

2D gel databases

OGPP54578.

Proteomic databases

PaxDbP54578.
PeptideAtlasP54578.
PRIDEP54578.

Protocols and materials databases

DNASU9097.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261601; ENSP00000261601; ENSG00000101557. [P54578-1]
ENST00000582707; ENSP00000464447; ENSG00000101557. [P54578-2]
GeneID9097.
KEGGhsa:9097.
UCSCuc002kkf.1. human. [P54578-1]

Organism-specific databases

CTD9097.
GeneCardsGC18P000148.
HGNCHGNC:12612. USP14.
HPAHPA001308.
MIM607274. gene.
neXtProtNX_P54578.
PharmGKBPA37238.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG286607.
HOGENOMHOG000202292.
HOVERGENHBG054185.
InParanoidP54578.
KOK11843.
OMAMRRELKC.
OrthoDBEOG7F7W8H.
PhylomeDBP54578.
TreeFamTF314494.

Gene expression databases

ArrayExpressP54578.
BgeeP54578.
CleanExHS_USP14.
GenevestigatorP54578.

Family and domain databases

InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR000626. Ubiquitin-like.
IPR019954. Ubiquitin_CS.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF00443. UCH. 1 hit.
[Graphical view]
SMARTSM00213. UBQ. 1 hit.
[Graphical view]
PROSITEPS00299. UBIQUITIN_1. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.
PS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP54578.
GeneWikiUSP14.
GenomeRNAi9097.
NextBio34093.
PROP54578.
SOURCESearch...

Entry information

Entry nameUBP14_HUMAN
AccessionPrimary (citable) accession number: P54578
Secondary accession number(s): J3QRZ5, Q53XY5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 138 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM