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Protein

Ubiquitin carboxyl-terminal hydrolase 14

Gene

USP14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).3 Publications

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).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei114Nucleophile1 Publication1
Active sitei435Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: ProtInc
  • endopeptidase inhibitor activity Source: UniProtKB
  • proteasome binding Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: FlyBase
  • tRNA guanylyltransferase activity Source: ProtInc

GO - Biological processi

  • chemical synaptic transmission Source: Ensembl
  • negative regulation of ER-associated ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
  • protein deubiquitination Source: FlyBase
  • regulation of chemotaxis Source: UniProtKB
  • regulation of proteasomal protein catabolic process Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:HS02289-MONOMER.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.

Protein family/group databases

MEROPSiC19.015.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:USP14
Synonyms:TGT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:12612. USP14.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cytoplasm Source: HPA
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell
  • proteasome complex Source: UniProtKB-KW
  • synapse Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Proteasome

Pathology & Biotechi

Organism-specific databases

DisGeNETi9097.
OpenTargetsiENSG00000101557.
PharmGKBiPA37238.

Chemistry databases

ChEMBLiCHEMBL1293295.
GuidetoPHARMACOLOGYi2429.

Polymorphism and mutation databases

BioMutaiUSP14.
DMDMi1729927.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806361 – 494Ubiquitin carboxyl-terminal hydrolase 14Add BLAST494

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52PhosphothreonineCombined sources1
Modified residuei143PhosphoserineCombined sources1
Modified residuei148PhosphoserineBy similarity1
Modified residuei235PhosphothreonineCombined sources1
Modified residuei237PhosphoserineCombined sources1
Modified residuei302PhosphoserineCombined sources1
Modified residuei432PhosphoserineCombined sources1
Modified residuei449N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP54578.
MaxQBiP54578.
PaxDbiP54578.
PeptideAtlasiP54578.
PRIDEiP54578.

2D gel databases

OGPiP54578.

PTM databases

iPTMnetiP54578.
PhosphoSitePlusiP54578.
SwissPalmiP54578.

Expressioni

Gene expression databases

BgeeiENSG00000101557.
CleanExiHS_USP14.
ExpressionAtlasiP54578. baseline and differential.
GenevisibleiP54578. HS.

Organism-specific databases

HPAiHPA001308.

Interactioni

Subunit structurei

Homodimer (Potential). Associates with the 26S proteasome. Interacts with FANCC, CXCR4 and ERN1.Curated3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PPP3CAQ082093EBI-1048016,EBI-352922

GO - Molecular functioni

  • proteasome binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114551. 72 interactors.
IntActiP54578. 32 interactors.
MINTiMINT-3020275.
STRINGi9606.ENSP00000261601.

Chemistry databases

BindingDBiP54578.

Structurei

Secondary structure

1494
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi110 – 112Combined sources3
Helixi114 – 124Combined sources11
Helixi127 – 134Combined sources8
Beta strandi144 – 147Combined sources4
Helixi148 – 166Combined sources19
Beta strandi168 – 170Combined sources3
Helixi173 – 182Combined sources10
Helixi184 – 187Combined sources4
Helixi200 – 212Combined sources13
Helixi242 – 246Combined sources5
Beta strandi249 – 260Combined sources12
Beta strandi269 – 278Combined sources10
Beta strandi280 – 282Combined sources3
Helixi286 – 292Combined sources7
Beta strandi297 – 301Combined sources5
Turni303 – 306Combined sources4
Beta strandi311 – 319Combined sources9
Beta strandi322 – 329Combined sources8
Beta strandi336 – 339Combined sources4
Beta strandi351 – 354Combined sources4
Helixi356 – 358Combined sources3
Helixi361 – 366Combined sources6
Turni367 – 371Combined sources5
Helixi372 – 374Combined sources3
Turni409 – 412Combined sources4
Beta strandi416 – 430Combined sources15
Beta strandi433 – 443Combined sources11
Beta strandi446 – 451Combined sources6
Beta strandi454 – 458Combined sources5
Helixi460 – 463Combined sources4
Helixi464 – 467Combined sources4
Beta strandi468 – 472Combined sources5
Beta strandi474 – 481Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AYNX-ray3.20A/B/C91-494[»]
2AYOX-ray3.50A91-494[»]
5GJQelectron microscopy4.50x1-494[»]
ProteinModelPortaliP54578.
SMRiP54578.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54578.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 80Ubiquitin-likePROSITE-ProRule annotationAdd BLAST77
Domaini105 – 483USPAdd BLAST379

Sequence similaritiesi

Contains 1 ubiquitin-like domain.PROSITE-ProRule annotation
Contains 1 USP domain.Curated

Phylogenomic databases

eggNOGiKOG1872. Eukaryota.
ENOG410XP96. LUCA.
GeneTreeiENSGT00390000009615.
HOGENOMiHOG000202292.
HOVERGENiHBG054185.
InParanoidiP54578.
KOiK11843.
OMAiFKVKVKW.
OrthoDBiEOG091G06MR.
PhylomeDBiP54578.
TreeFamiTF314494.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR029071. Ubiquitin-rel_dom.
IPR019954. Ubiquitin_CS.
IPR000626. Ubiquitin_dom.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
SMARTiSM00213. UBQ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS00299. 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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P54578-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPLYSVTVKW GKEKFEGVEL NTDEPPMVFK AQLFALTGVQ PARQKVMVKG
60 70 80 90 100
GTLKDDDWGN IKIKNGMTLL MMGSADALPE EPSAKTVFVE DMTEEQLASA
110 120 130 140 150
MELPCGLTNL GNTCYMNATV QCIRSVPELK DALKRYAGAL RASGEMASAQ
160 170 180 190 200
YITAALRDLF DSMDKTSSSI PPIILLQFLH MAFPQFAEKG EQGQYLQQDA
210 220 230 240 250
NECWIQMMRV LQQKLEAIED DSVKETDSSS ASAATPSKKK SLIDQFFGVE
260 270 280 290 300
FETTMKCTES EEEEVTKGKE NQLQLSCFIN QEVKYLFTGL KLRLQEEITK
310 320 330 340 350
QSPTLQRNAL YIKSSKISRL PAYLTIQMVR FFYKEKESVN AKVLKDVKFP
360 370 380 390 400
LMLDMYELCT PELQEKMVSF RSKFKDLEDK KVNQQPNTSD KKSSPQKEVK
410 420 430 440 450
YEPFSFADDI GSNNCGYYDL QAVLTHQGRS SSSGHYVSWV KRKQDEWIKF
460 470 480 490
DDDKVSIVTP EDILRLSGGG DWHIAYVLLY GPRRVEIMEE ESEQ
Length:494
Mass (Da):56,069
Last modified:January 23, 2007 - v3
Checksum:iE6D4679A86E9DF00
GO
Isoform 2 (identifier: P54578-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     66-100: Missing.

Note: No experimental confirmation available.
Show »
Length:459
Mass (Da):52,386
Checksum:i3EDE73254891B166
GO
Isoform 3 (identifier: P54578-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     55-65: Missing.

Note: No experimental confirmation available.
Show »
Length:483
Mass (Da):54,770
Checksum:iB57991EE5A5CCA4E
GO

Sequence cautioni

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

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05729255 – 65Missing in isoform 3. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_04734366 – 100Missing in isoform 2. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U30888 mRNA. Translation: AAB60365.1.
BT007183 mRNA. Translation: AAP35847.1.
AK297605 mRNA. Translation: BAH12624.1.
AP000845 Genomic DNA. No translation available.
BC003556 mRNA. Translation: AAH03556.1.
CR976282 mRNA. No translation available.
CCDSiCCDS32780.1. [P54578-1]
CCDS32781.1. [P54578-2]
PIRiG01932.
RefSeqiNP_001032411.1. NM_001037334.1. [P54578-2]
NP_005142.1. NM_005151.3. [P54578-1]
UniGeneiHs.464416.
Hs.707058.

Genome annotation databases

EnsembliENST00000261601; ENSP00000261601; ENSG00000101557. [P54578-1]
ENST00000400266; ENSP00000383125; ENSG00000101557. [P54578-3]
ENST00000582707; ENSP00000464447; ENSG00000101557. [P54578-2]
GeneIDi9097.
KEGGihsa:9097.
UCSCiuc002kkf.2. human. [P54578-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U30888 mRNA. Translation: AAB60365.1.
BT007183 mRNA. Translation: AAP35847.1.
AK297605 mRNA. Translation: BAH12624.1.
AP000845 Genomic DNA. No translation available.
BC003556 mRNA. Translation: AAH03556.1.
CR976282 mRNA. No translation available.
CCDSiCCDS32780.1. [P54578-1]
CCDS32781.1. [P54578-2]
PIRiG01932.
RefSeqiNP_001032411.1. NM_001037334.1. [P54578-2]
NP_005142.1. NM_005151.3. [P54578-1]
UniGeneiHs.464416.
Hs.707058.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AYNX-ray3.20A/B/C91-494[»]
2AYOX-ray3.50A91-494[»]
5GJQelectron microscopy4.50x1-494[»]
ProteinModelPortaliP54578.
SMRiP54578.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114551. 72 interactors.
IntActiP54578. 32 interactors.
MINTiMINT-3020275.
STRINGi9606.ENSP00000261601.

Chemistry databases

BindingDBiP54578.
ChEMBLiCHEMBL1293295.
GuidetoPHARMACOLOGYi2429.

Protein family/group databases

MEROPSiC19.015.

PTM databases

iPTMnetiP54578.
PhosphoSitePlusiP54578.
SwissPalmiP54578.

Polymorphism and mutation databases

BioMutaiUSP14.
DMDMi1729927.

2D gel databases

OGPiP54578.

Proteomic databases

EPDiP54578.
MaxQBiP54578.
PaxDbiP54578.
PeptideAtlasiP54578.
PRIDEiP54578.

Protocols and materials databases

DNASUi9097.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261601; ENSP00000261601; ENSG00000101557. [P54578-1]
ENST00000400266; ENSP00000383125; ENSG00000101557. [P54578-3]
ENST00000582707; ENSP00000464447; ENSG00000101557. [P54578-2]
GeneIDi9097.
KEGGihsa:9097.
UCSCiuc002kkf.2. human. [P54578-1]

Organism-specific databases

CTDi9097.
DisGeNETi9097.
GeneCardsiUSP14.
HGNCiHGNC:12612. USP14.
HPAiHPA001308.
MIMi607274. gene.
neXtProtiNX_P54578.
OpenTargetsiENSG00000101557.
PharmGKBiPA37238.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1872. Eukaryota.
ENOG410XP96. LUCA.
GeneTreeiENSGT00390000009615.
HOGENOMiHOG000202292.
HOVERGENiHBG054185.
InParanoidiP54578.
KOiK11843.
OMAiFKVKVKW.
OrthoDBiEOG091G06MR.
PhylomeDBiP54578.
TreeFamiTF314494.

Enzyme and pathway databases

BioCyciZFISH:HS02289-MONOMER.
ReactomeiR-HSA-5689880. Ub-specific processing proteases.

Miscellaneous databases

ChiTaRSiUSP14. human.
EvolutionaryTraceiP54578.
GeneWikiiUSP14.
GenomeRNAii9097.
PROiP54578.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101557.
CleanExiHS_USP14.
ExpressionAtlasiP54578. baseline and differential.
GenevisibleiP54578. HS.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR029071. Ubiquitin-rel_dom.
IPR019954. Ubiquitin_CS.
IPR000626. Ubiquitin_dom.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
SMARTiSM00213. UBQ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS00299. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiUBP14_HUMAN
AccessioniPrimary (citable) accession number: P54578
Secondary accession number(s): B7Z4N8, J3QRZ5, Q53XY5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 165 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Caution

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. 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.