UniProtKB - P54578 (UBP14_HUMAN)
Protein
Ubiquitin carboxyl-terminal hydrolase 14
Gene
USP14
Organism
Homo sapiens (Human)
Status
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 EC:3.4.19.12
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 114 | Nucleophile1 Publication | 1 | |
Active sitei | 435 | Proton acceptorPROSITE-ProRule annotation | 1 |
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: UniProtKB
GO - Biological processi
- chemical synaptic transmission Source: Ensembl
- innate immune response Source: UniProtKB-KW
- 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
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Immunity, Innate immunity, Ubl conjugation pathway |
Enzyme and pathway databases
PathwayCommonsi | P54578 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases |
Protein family/group databases
MEROPSi | C19.015 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:12612, USP14 |
MIMi | 607274, gene |
neXtProti | NX_P54578 |
VEuPathDBi | HostDB:ENSG00000101557.14 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Peripheral membrane protein 1 Publication
Other locations
- Cytoplasm 1 Publication
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Nucleus
- nucleus Source: GO_Central
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
- cell surface Source: UniProtKB
- cytoplasmic vesicle Source: UniProtKB
- proteasome complex Source: UniProtKB-KW
- synapse Source: Ensembl
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Membrane, ProteasomePathology & Biotechi
Organism-specific databases
DisGeNETi | 9097 |
OpenTargetsi | ENSG00000101557 |
PharmGKBi | PA37238 |
Miscellaneous databases
Pharosi | P54578, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1293295 |
DrugBanki | DB12695, Phenethyl Isothiocyanate |
GuidetoPHARMACOLOGYi | 2429 |
Genetic variation databases
BioMutai | USP14 |
DMDMi | 1729927 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080636 | 1 – 494 | Ubiquitin carboxyl-terminal hydrolase 14Add BLAST | 494 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 52 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 143 | PhosphoserineCombined sources | 1 | |
Modified residuei | 148 | PhosphoserineBy similarity | 1 | |
Modified residuei | 235 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 237 | PhosphoserineCombined sources | 1 | |
Modified residuei | 302 | PhosphoserineCombined sources | 1 | |
Modified residuei | 432 | PhosphoserineCombined sources | 1 | |
Modified residuei | 449 | N6-acetyllysineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P54578 |
jPOSTi | P54578 |
MassIVEi | P54578 |
MaxQBi | P54578 |
PaxDbi | P54578 |
PeptideAtlasi | P54578 |
PRIDEi | P54578 |
ProteomicsDBi | 56687 [P54578-1] 6620 |
2D gel databases
OGPi | P54578 |
PTM databases
iPTMneti | P54578 |
MetOSitei | P54578 |
PhosphoSitePlusi | P54578 |
SwissPalmi | P54578 |
Expressioni
Gene expression databases
Bgeei | ENSG00000101557, Expressed in secondary oocyte and 258 other tissues |
ExpressionAtlasi | P54578, baseline and differential |
Genevisiblei | P54578, HS |
Organism-specific databases
HPAi | ENSG00000101557, Low tissue specificity |
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 PublicationsBinary interactionsi
P54578
With | #Exp. | IntAct |
---|---|---|
PPP3CA [Q08209] | 3 | EBI-1048016,EBI-352922 |
Protein-protein interaction databases
BioGRIDi | 114551, 416 interactors |
IntActi | P54578, 47 interactors |
MINTi | P54578 |
STRINGi | 9606.ENSP00000261601 |
Chemistry databases
BindingDBi | P54578 |
Miscellaneous databases
RNActi | P54578, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P54578 |
SMRi | P54578 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P54578 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 4 – 80 | Ubiquitin-likePROSITE-ProRule annotationAdd BLAST | 77 | |
Domaini | 105 – 483 | USPAdd BLAST | 379 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1872, Eukaryota |
GeneTreei | ENSGT00390000009615 |
InParanoidi | P54578 |
OMAi | NNSGYYE |
OrthoDBi | 600543at2759 |
PhylomeDBi | P54578 |
TreeFami | TF314494 |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR000626, Ubiquitin-like_dom IPR029071, Ubiquitin-like_domsf IPR019954, Ubiquitin_CS IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit |
SMARTi | View protein in SMART SM00213, UBQ, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit SSF54236, SSF54236, 1 hit |
PROSITEi | View 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 |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P54578-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA6NJA2 | A6NJA2_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP14 | 448 | Annotation score: | ||
J3KS55 | J3KS55_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP14 | 28 | Annotation score: | ||
J3QQT6 | J3QQT6_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP14 | 20 | Annotation score: | ||
R4GNB0 | R4GNB0_HUMAN | Ubiquitin carboxyl-terminal hydrola... | USP14 | 33 | Annotation score: |
Sequence cautioni
The sequence CR976282 differs from that shown. Reason: Frameshift.Curated
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_057292 | 55 – 65 | Missing in isoform 3. 1 PublicationAdd BLAST | 11 | |
Alternative sequenceiVSP_047343 | 66 – 100 | Missing in isoform 2. 1 PublicationAdd BLAST | 35 |
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. |
CCDSi | CCDS32780.1 [P54578-1] CCDS32781.1 [P54578-2] |
PIRi | G01932 |
RefSeqi | NP_001032411.1, NM_001037334.1 [P54578-2] NP_005142.1, NM_005151.3 [P54578-1] |
Genome annotation databases
Ensembli | ENST00000261601; ENSP00000261601; ENSG00000101557 [P54578-1] ENST00000400266; ENSP00000383125; ENSG00000101557 [P54578-3] ENST00000582707; ENSP00000464447; ENSG00000101557 [P54578-2] |
GeneIDi | 9097 |
KEGGi | hsa:9097 |
UCSCi | uc002kkf.2, human [P54578-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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. |
CCDSi | CCDS32780.1 [P54578-1] CCDS32781.1 [P54578-2] |
PIRi | G01932 |
RefSeqi | NP_001032411.1, NM_001037334.1 [P54578-2] NP_005142.1, NM_005151.3 [P54578-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2AYN | X-ray | 3.20 | A/B/C | 91-494 | [»] | |
2AYO | X-ray | 3.50 | A | 91-494 | [»] | |
5GJQ | electron microscopy | 4.50 | x | 1-494 | [»] | |
6IIK | X-ray | 1.97 | A/B | 96-494 | [»] | |
6IIL | X-ray | 2.20 | A/B | 96-494 | [»] | |
6IIM | X-ray | 2.21 | A/B | 96-494 | [»] | |
6IIN | X-ray | 2.53 | A/B | 101-485 | [»] | |
6LVS | X-ray | 2.73 | A/B/C/D/E/F | 92-494 | [»] | |
BMRBi | P54578 | |||||
SMRi | P54578 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114551, 416 interactors |
IntActi | P54578, 47 interactors |
MINTi | P54578 |
STRINGi | 9606.ENSP00000261601 |
Chemistry databases
BindingDBi | P54578 |
ChEMBLi | CHEMBL1293295 |
DrugBanki | DB12695, Phenethyl Isothiocyanate |
GuidetoPHARMACOLOGYi | 2429 |
Protein family/group databases
MEROPSi | C19.015 |
PTM databases
iPTMneti | P54578 |
MetOSitei | P54578 |
PhosphoSitePlusi | P54578 |
SwissPalmi | P54578 |
Genetic variation databases
BioMutai | USP14 |
DMDMi | 1729927 |
2D gel databases
OGPi | P54578 |
Proteomic databases
EPDi | P54578 |
jPOSTi | P54578 |
MassIVEi | P54578 |
MaxQBi | P54578 |
PaxDbi | P54578 |
PeptideAtlasi | P54578 |
PRIDEi | P54578 |
ProteomicsDBi | 56687 [P54578-1] 6620 |
Protocols and materials databases
Antibodypediai | 676, 294 antibodies |
DNASUi | 9097 |
Genome annotation databases
Ensembli | ENST00000261601; ENSP00000261601; ENSG00000101557 [P54578-1] ENST00000400266; ENSP00000383125; ENSG00000101557 [P54578-3] ENST00000582707; ENSP00000464447; ENSG00000101557 [P54578-2] |
GeneIDi | 9097 |
KEGGi | hsa:9097 |
UCSCi | uc002kkf.2, human [P54578-1] |
Organism-specific databases
CTDi | 9097 |
DisGeNETi | 9097 |
GeneCardsi | USP14 |
HGNCi | HGNC:12612, USP14 |
HPAi | ENSG00000101557, Low tissue specificity |
MIMi | 607274, gene |
neXtProti | NX_P54578 |
OpenTargetsi | ENSG00000101557 |
PharmGKBi | PA37238 |
VEuPathDBi | HostDB:ENSG00000101557.14 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1872, Eukaryota |
GeneTreei | ENSGT00390000009615 |
InParanoidi | P54578 |
OMAi | NNSGYYE |
OrthoDBi | 600543at2759 |
PhylomeDBi | P54578 |
TreeFami | TF314494 |
Enzyme and pathway databases
PathwayCommonsi | P54578 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases |
Miscellaneous databases
BioGRID-ORCSi | 9097, 80 hits in 876 CRISPR screens |
ChiTaRSi | USP14, human |
EvolutionaryTracei | P54578 |
GeneWikii | USP14 |
GenomeRNAii | 9097 |
Pharosi | P54578, Tchem |
PROi | PR:P54578 |
RNActi | P54578, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000101557, Expressed in secondary oocyte and 258 other tissues |
ExpressionAtlasi | P54578, baseline and differential |
Genevisiblei | P54578, HS |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR000626, Ubiquitin-like_dom IPR029071, Ubiquitin-like_domsf IPR019954, Ubiquitin_CS IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit |
SMARTi | View protein in SMART SM00213, UBQ, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit SSF54236, SSF54236, 1 hit |
PROSITEi | View 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | UBP14_HUMAN | |
Accessioni | P54578Primary (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: | February 10, 2021 | |
This is version 201 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome 18
Human chromosome 18: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families