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Protein

Ubiquitin carboxyl-terminal hydrolase 5

Gene

USP5

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

Functioni

Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. Involved in unanchored 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys-63'-linked polyubiquitin with a lower affinity. Knock-down of USP5 causes the accumulation of p53/TP53 and an increase in p53/TP53 transcriptional activity because the unanchored polyubiquitin that accumulates is able to compete with ubiquitinated p53/TP53 but not with MDM2 for proteasomal recognition.1 Publication

Miscellaneous

The UBP-type zinc finger domain crystallizes as a dimer linked by a disulfide bond between the Cys-195 residues of both molecules, but there is no evidence that the full-length USP5 exists as a dimer.

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).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi199Zinc1
Metal bindingi202Zinc1
Binding sitei209Substrate1
Metal bindingi219Zinc1
Metal bindingi232Zinc1
Binding sitei259Substrate1
Binding sitei261Substrate; via carbonyl oxygen1
Binding sitei264Substrate1
Active sitei335Nucleophile1
Active sitei818Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri197 – 269UBP-typePROSITE-ProRule annotationAdd BLAST73

GO - Molecular functioni

  • cysteine-type endopeptidase activity Source: GO_Central
  • thiol-dependent ubiquitin-specific protease activity Source: ParkinsonsUK-UCL
  • thiol-dependent ubiquitinyl hydrolase activity Source: Reactome
  • ubiquitin binding Source: ParkinsonsUK-UCL
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.19.12 2681
ReactomeiR-HSA-5689880 Ub-specific processing proteases
R-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes

Protein family/group databases

MEROPSiC19.001

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin carboxyl-terminal hydrolase 5 (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme 5
Isopeptidase T
Ubiquitin thioesterase 5
Ubiquitin-specific-processing protease 5
Gene namesi
Name:USP5
Synonyms:ISOT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000111667.13
HGNCiHGNC:12628 USP5
MIMi601447 gene
neXtProtiNX_P45974

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi199C → A: Decreased rate of activity and decreased zinc binding. 1 Publication1
Mutagenesisi202C → A: Decreased rate of activity. 1 Publication1
Mutagenesisi219C → A: Decreased rate of activity. 1 Publication1
Mutagenesisi221 – 223RRY → KWF: Loss of polyubiquitin binding and subsequent activation. 1 Publication3
Mutagenesisi221R → A: Loss of polyubiquitin hydrolysis. Loss of ubiquitin binding; when associated with A-335. 1 Publication1
Mutagenesisi232H → A: Decreased rate of activity. 1 Publication1
Mutagenesisi261Y → F: Loss of polyubiquitin binding. 1 Publication1
Mutagenesisi335C → A: Loss of activity. Loss of ubiquitin binding; when associated with A-221. Lower affinity for triubiquitin and tetraubiquitin, but no effect on affinity for diubiquitin; when associated with E-666. Lower affinity for diubiquitin, triubiquitin and tetraubiquitin; when associated with E-734. 1 Publication1
Mutagenesisi435D → A: Loss of polyubiquitin binding and hydrolysis. 1 Publication1
Mutagenesisi666M → E: Lower affinity for triubiquitin and tetraubiquitin, but no effect on affinity for diubiquitin; when associated with A-335. No effect on activity; when associated with E-734. 1 Publication1
Mutagenesisi734M → E: Lower affinity for diubiquitin, triubiquitin and tetraubiquitin; when associated with A-335. No effect on activity; when associated with E-666. 1 Publication1

Organism-specific databases

DisGeNETi8078
OpenTargetsiENSG00000111667
PharmGKBiPA37253

Chemistry databases

ChEMBLiCHEMBL6158
GuidetoPHARMACOLOGYi2431

Polymorphism and mutation databases

BioMutaiUSP5
DMDMi1717869

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000806232 – 858Ubiquitin carboxyl-terminal hydrolase 5Add BLAST857

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei156PhosphoserineCombined sources1
Disulfide bondi195 ↔ 8161 Publication
Modified residuei292PhosphothreonineCombined sources1
Modified residuei623PhosphothreonineBy similarity1
Modified residuei779PhosphoserineCombined sources1
Modified residuei783PhosphoserineCombined sources1
Modified residuei785PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP45974
MaxQBiP45974
PaxDbiP45974
PeptideAtlasiP45974
PRIDEiP45974
ProteomicsDBi55692
55693 [P45974-2]

2D gel databases

REPRODUCTION-2DPAGEiIPI00375145

PTM databases

iPTMnetiP45974
PhosphoSitePlusiP45974
SwissPalmiP45974

Miscellaneous databases

PMAP-CutDBiP45974

Expressioni

Gene expression databases

BgeeiENSG00000111667 Expressed in 217 organ(s), highest expression level in frontal cortex
CleanExiHS_USP5
ExpressionAtlasiP45974 baseline and differential
GenevisibleiP45974 HS

Organism-specific databases

HPAiHPA006756

Interactioni

Subunit structurei

Interacts with TRIML1.By similarity

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113751, 84 interactors
DIPiDIP-34459N
IntActiP45974, 13 interactors
MINTiP45974
STRINGi9606.ENSP00000229268

Chemistry databases

BindingDBiP45974

Structurei

Secondary structure

1858
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP45974
SMRiP45974
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP45974

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini326 – 856USPAdd BLAST531
Domaini654 – 695UBA 1PROSITE-ProRule annotationAdd BLAST42
Domaini722 – 762UBA 2PROSITE-ProRule annotationAdd BLAST41

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni221 – 224Substrate binding4

Domaini

The UBP-type zinc finger domain interacts selectively with an unmodified C-terminus of the proximal ubiquitin. Both UBA domains are involved in polyubiquitin recognition.

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri197 – 269UBP-typePROSITE-ProRule annotationAdd BLAST73

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0944 Eukaryota
COG5207 LUCA
GeneTreeiENSGT00390000000874
HOGENOMiHOG000162311
HOVERGENiHBG002833
InParanoidiP45974
KOiK11836
OMAiQYVERHY
OrthoDBiEOG091G01W3
PhylomeDBiP45974
TreeFamiTF300576

Family and domain databases

Gene3Di3.30.40.10, 3 hits
InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR015940 UBA
IPR009060 UBA-like_sf
IPR016652 Ubiquitinyl_hydrolase
IPR018200 USP_CS
IPR028889 USP_dom
IPR013083 Znf_RING/FYVE/PHD
IPR001607 Znf_UBP
PfamiView protein in Pfam
PF00627 UBA, 2 hits
PF00443 UCH, 1 hit
PF02148 zf-UBP, 1 hit
PIRSFiPIRSF016308 UBP, 1 hit
SMARTiView protein in SMART
SM00165 UBA, 2 hits
SM00290 ZnF_UBP, 1 hit
SUPFAMiSSF46934 SSF46934, 1 hit
SSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS50030 UBA, 2 hits
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
PS50271 ZF_UBP, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform Long (identifier: P45974-1) [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
MAELSEEALL SVLPTIRVPK AGDRVHKDEC AFSFDTPESE GGLYICMNTF
60 70 80 90 100
LGFGKQYVER HFNKTGQRVY LHLRRTRRPK EEDPATGTGD PPRKKPTRLA
110 120 130 140 150
IGVEGGFDLS EEKFELDEDV KIVILPDYLE IARDGLGGLP DIVRDRVTSA
160 170 180 190 200
VEALLSADSA SRKQEVQAWD GEVRQVSKHA FSLKQLDNPA RIPPCGWKCS
210 220 230 240 250
KCDMRENLWL NLTDGSILCG RRYFDGSGGN NHAVEHYRET GYPLAVKLGT
260 270 280 290 300
ITPDGADVYS YDEDDMVLDP SLAEHLSHFG IDMLKMQKTD KTMTELEIDM
310 320 330 340 350
NQRIGEWELI QESGVPLKPL FGPGYTGIRN LGNSCYLNSV VQVLFSIPDF
360 370 380 390 400
QRKYVDKLEK IFQNAPTDPT QDFSTQVAKL GHGLLSGEYS KPVPESGDGE
410 420 430 440 450
RVPEQKEVQD GIAPRMFKAL IGKGHPEFST NRQQDAQEFF LHLINMVERN
460 470 480 490 500
CRSSENPNEV FRFLVEEKIK CLATEKVKYT QRVDYIMQLP VPMDAALNKE
510 520 530 540 550
ELLEYEEKKR QAEEEKMALP ELVRAQVPFS SCLEAYGAPE QVDDFWSTAL
560 570 580 590 600
QAKSVAVKTT RFASFPDYLV IQIKKFTFGL DWVPKKLDVS IEMPEELDIS
610 620 630 640 650
QLRGTGLQPG EEELPDIAPP LVTPDEPKGS LGFYGNEDED SFCSPHFSSP
660 670 680 690 700
TSPMLDESVI IQLVEMGFPM DACRKAVYYT GNSGAEAAMN WVMSHMDDPD
710 720 730 740 750
FANPLILPGS SGPGSTSAAA DPPPEDCVTT IVSMGFSRDQ ALKALRATNN
760 770 780 790 800
SLERAVDWIF SHIDDLDAEA AMDISEGRSA ADSISESVPV GPKVRDGPGK
810 820 830 840 850
YQLFAFISHM GTSTMCGHYV CHIKKEGRWV IYNDQKVCAS EKPPKDLGYI

YFYQRVAS
Length:858
Mass (Da):95,786
Last modified:October 1, 1996 - v2
Checksum:iE99CB7CDFA682C65
GO
Isoform Short (identifier: P45974-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     629-652: GSLGFYGNEDEDSFCSPHFSSPTS → A

Show »
Length:835
Mass (Da):93,308
Checksum:i227CB29B11C7DAEA
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H571F5H571_HUMAN
Ubiquitin carboxyl-terminal hydrola...
USP5
137Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3 – 4EL → DV in CAA62690 (PubMed:7498549).Curated2
Sequence conflicti45I → V in CAA62690 (PubMed:7498549).Curated1
Sequence conflicti468K → R in AAA78934 (Ref. 4) Curated1
Sequence conflicti681G → D in AAA78934 (Ref. 4) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005259629 – 652GSLGF…SSPTS → A in isoform Short. 1 PublicationAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X91349 mRNA Translation: CAA62690.1
U47927 mRNA Translation: AAC50465.1
U47924 Genomic DNA Translation: AAB51314.1
U47924 Genomic DNA Translation: AAB51315.1
U35116 mRNA Translation: AAA78934.1
CH471116 Genomic DNA Translation: EAW88724.1
CH471116 Genomic DNA Translation: EAW88725.1
CH471116 Genomic DNA Translation: EAW88726.1
CH471116 Genomic DNA Translation: EAW88727.1
BC004889 mRNA Translation: AAH04889.1
BC005139 mRNA Translation: AAH05139.1
CCDSiCCDS31733.1 [P45974-2]
CCDS41743.1 [P45974-1]
PIRiS68227
RefSeqiNP_001092006.1, NM_001098536.1 [P45974-1]
NP_003472.2, NM_003481.2 [P45974-2]
UniGeneiHs.631661

Genome annotation databases

EnsembliENST00000229268; ENSP00000229268; ENSG00000111667 [P45974-1]
ENST00000389231; ENSP00000373883; ENSG00000111667 [P45974-2]
GeneIDi8078
KEGGihsa:8078
UCSCiuc001qrh.5 human [P45974-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X91349 mRNA Translation: CAA62690.1
U47927 mRNA Translation: AAC50465.1
U47924 Genomic DNA Translation: AAB51314.1
U47924 Genomic DNA Translation: AAB51315.1
U35116 mRNA Translation: AAA78934.1
CH471116 Genomic DNA Translation: EAW88724.1
CH471116 Genomic DNA Translation: EAW88725.1
CH471116 Genomic DNA Translation: EAW88726.1
CH471116 Genomic DNA Translation: EAW88727.1
BC004889 mRNA Translation: AAH04889.1
BC005139 mRNA Translation: AAH05139.1
CCDSiCCDS31733.1 [P45974-2]
CCDS41743.1 [P45974-1]
PIRiS68227
RefSeqiNP_001092006.1, NM_001098536.1 [P45974-1]
NP_003472.2, NM_003481.2 [P45974-2]
UniGeneiHs.631661

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DAGNMR-A655-715[»]
2DAKNMR-A723-772[»]
2G43X-ray2.09A/B163-291[»]
2G45X-ray1.99A/D163-291[»]
3IHPX-ray2.80A/B1-858[»]
6DXHX-ray2.00A171-290[»]
6DXTX-ray1.95A/B171-290[»]
ProteinModelPortaliP45974
SMRiP45974
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113751, 84 interactors
DIPiDIP-34459N
IntActiP45974, 13 interactors
MINTiP45974
STRINGi9606.ENSP00000229268

Chemistry databases

BindingDBiP45974
ChEMBLiCHEMBL6158
GuidetoPHARMACOLOGYi2431

Protein family/group databases

MEROPSiC19.001

PTM databases

iPTMnetiP45974
PhosphoSitePlusiP45974
SwissPalmiP45974

Polymorphism and mutation databases

BioMutaiUSP5
DMDMi1717869

2D gel databases

REPRODUCTION-2DPAGEiIPI00375145

Proteomic databases

EPDiP45974
MaxQBiP45974
PaxDbiP45974
PeptideAtlasiP45974
PRIDEiP45974
ProteomicsDBi55692
55693 [P45974-2]

Protocols and materials databases

DNASUi8078
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000229268; ENSP00000229268; ENSG00000111667 [P45974-1]
ENST00000389231; ENSP00000373883; ENSG00000111667 [P45974-2]
GeneIDi8078
KEGGihsa:8078
UCSCiuc001qrh.5 human [P45974-1]

Organism-specific databases

CTDi8078
DisGeNETi8078
EuPathDBiHostDB:ENSG00000111667.13
GeneCardsiUSP5
HGNCiHGNC:12628 USP5
HPAiHPA006756
MIMi601447 gene
neXtProtiNX_P45974
OpenTargetsiENSG00000111667
PharmGKBiPA37253
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0944 Eukaryota
COG5207 LUCA
GeneTreeiENSGT00390000000874
HOGENOMiHOG000162311
HOVERGENiHBG002833
InParanoidiP45974
KOiK11836
OMAiQYVERHY
OrthoDBiEOG091G01W3
PhylomeDBiP45974
TreeFamiTF300576

Enzyme and pathway databases

BRENDAi3.4.19.12 2681
ReactomeiR-HSA-5689880 Ub-specific processing proteases
R-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes

Miscellaneous databases

ChiTaRSiUSP5 human
EvolutionaryTraceiP45974
GeneWikiiUSP5
GenomeRNAii8078
PMAP-CutDBiP45974
PROiPR:P45974
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111667 Expressed in 217 organ(s), highest expression level in frontal cortex
CleanExiHS_USP5
ExpressionAtlasiP45974 baseline and differential
GenevisibleiP45974 HS

Family and domain databases

Gene3Di3.30.40.10, 3 hits
InterProiView protein in InterPro
IPR038765 Papain_like_cys_pep_sf
IPR001394 Peptidase_C19_UCH
IPR015940 UBA
IPR009060 UBA-like_sf
IPR016652 Ubiquitinyl_hydrolase
IPR018200 USP_CS
IPR028889 USP_dom
IPR013083 Znf_RING/FYVE/PHD
IPR001607 Znf_UBP
PfamiView protein in Pfam
PF00627 UBA, 2 hits
PF00443 UCH, 1 hit
PF02148 zf-UBP, 1 hit
PIRSFiPIRSF016308 UBP, 1 hit
SMARTiView protein in SMART
SM00165 UBA, 2 hits
SM00290 ZnF_UBP, 1 hit
SUPFAMiSSF46934 SSF46934, 1 hit
SSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS50030 UBA, 2 hits
PS00972 USP_1, 1 hit
PS00973 USP_2, 1 hit
PS50235 USP_3, 1 hit
PS50271 ZF_UBP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiUBP5_HUMAN
AccessioniPrimary (citable) accession number: P45974
Secondary accession number(s): D3DUS7, D3DUS8, Q96J22
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: October 1, 1996
Last modified: November 7, 2018
This is version 190 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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