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Protein

Ubiquitin carboxyl-terminal hydrolase 14

Gene

USP14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation.4 Publications

Caution

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

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
  • thiol-dependent ubiquitinyl hydrolase activity Source: UniProtKB
  • tRNA guanylyltransferase activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processImmunity, Innate immunity, Ubl conjugation pathway

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000101557.14
HGNCiHGNC:12612 USP14
MIMi607274 gene
neXtProtiNX_P54578

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi56687

2D gel databases

OGPiP54578

PTM databases

iPTMnetiP54578
PhosphoSitePlusiP54578
SwissPalmiP54578

Expressioni

Gene expression databases

BgeeiENSG00000101557 Expressed in 246 organ(s), highest expression level in secondary oocyte
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. Interacts with TRIM14; this interaction recruits USP14 to cleave ubiquitin chains of CGAS.Curated4 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi114551, 78 interactors
IntActiP54578, 33 interactors
MINTiP54578
STRINGi9606.ENSP00000261601

Chemistry databases

BindingDBiP54578

Structurei

Secondary structure

1494
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR029071 Ubiquitin-like_domsf
IPR019954 Ubiquitin_CS
IPR000626 Ubiquitin_dom
IPR018200 USP_CS
IPR028889 USP_dom
PfamiView protein in Pfam
PF00443 UCH, 1 hit
SMARTiView protein in SMART
SM00213 UBQ, 1 hit
SUPFAMiSSF54001 SSF54001, 1 hit
SSF54236 SSF54236, 1 hit
PROSITEiView protein in PROSITE
PS00299 UBIQUITIN_1, 1 hit
PS50053 UBIQUITIN_2, 1 hit
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A6NJA2A6NJA2_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP14
448Annotation score:
J3KS55J3KS55_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP14
28Annotation score:
J3QQT6J3QQT6_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP14
20Annotation score:
R4GNB0R4GNB0_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP14
33Annotation score:

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

Similar proteinsi

Entry informationi

Entry nameiUBP14_HUMAN
AccessioniPrimary (citable) accession number: P54578
Secondary accession number(s): B7Z4N8, J3QRZ5, Q53XY5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 181 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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