Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ubiquitin carboxyl-terminal hydrolase 5

Gene

USP5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 acceptorIEP:1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri197 – 269UBP-typeIEP:Add BLAST73

GO - Molecular functioni

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.

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 methionineiRemovedND:
ChainiPRO_00000806232 – 858Ubiquitin carboxyl-terminal hydrolase 5Add BLAST857

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineND:1
Modified residuei156PhosphoserineND:1
Disulfide bondi195 ↔ 8161 Publication
Modified residuei292PhosphothreonineND:1
Modified residuei623PhosphothreonineHMP:1
Modified residuei779PhosphoserineND:1
Modified residuei783PhosphoserineND:1
Modified residuei785PhosphoserineND:1

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP45974.
MaxQBiP45974.
PaxDbiP45974.
PeptideAtlasiP45974.
PRIDEiP45974.

2D gel databases

REPRODUCTION-2DPAGEiIPI00375145.

PTM databases

iPTMnetiP45974.
PhosphoSitePlusiP45974.
SwissPalmiP45974.

Miscellaneous databases

PMAP-CutDBiP45974.

Expressioni

Gene expression databases

BgeeiENSG00000111667.
CleanExiHS_USP5.
ExpressionAtlasiP45974. baseline and differential.
GenevisibleiP45974. HS.

Organism-specific databases

HPAiHPA006756.

Interactioni

Subunit structurei

Interacts with TRIML1.HMP:

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113751. 81 interactors.
DIPiDIP-34459N.
IntActiP45974. 13 interactors.
MINTiMINT-5001006.
STRINGi9606.ENSP00000229268.

Chemistry databases

BindingDBiP45974.

Structurei

Secondary structure

1858
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 11ND:7
Helixi12 – 15ND:4
Beta strandi31 – 34ND:4
Beta strandi43 – 46ND:4
Turni47 – 49ND:3
Turni55 – 57ND:3
Helixi58 – 65ND:8
Beta strandi69 – 75ND:7
Beta strandi118 – 124ND:7
Turni125 – 128ND:4
Beta strandi129 – 131ND:3
Helixi141 – 154ND:14
Turni178 – 182ND:5
Beta strandi200 – 203ND:4
Beta strandi206 – 211ND:6
Turni212 – 214ND:3
Beta strandi217 – 219ND:3
Helixi232 – 240ND:9
Beta strandi244 – 247ND:4
Beta strandi258 – 260ND:3
Turni261 – 264ND:4
Beta strandi265 – 268ND:4
Helixi272 – 277ND:6
Turni278 – 280ND:3
Turni283 – 285ND:3
Helixi335 – 344ND:10
Helixi348 – 354ND:7
Turni355 – 357ND:3
Helixi358 – 364ND:7
Helixi369 – 371ND:3
Helixi373 – 385ND:13
Helixi415 – 421ND:7
Turni422 – 424ND:3
Turni426 – 429ND:4
Beta strandi430 – 432ND:3
Helixi436 – 449ND:14
Helixi457 – 460ND:4
Beta strandi463 – 471ND:9
Turni472 – 475ND:4
Beta strandi476 – 489ND:14
Helixi493 – 495ND:3
Helixi499 – 514ND:16
Helixi529 – 537ND:9
Beta strandi540 – 547ND:8
Turni548 – 551ND:4
Beta strandi552 – 564ND:13
Beta strandi567 – 573ND:7
Beta strandi576 – 578ND:3
Helixi580 – 582ND:3
Beta strandi584 – 586ND:3
Beta strandi595 – 598ND:4
Helixi600 – 602ND:3
Helixi658 – 666ND:9
Helixi670 – 679ND:10
Helixi685 – 695ND:11
Helixi700 – 702ND:3
Helixi725 – 732ND:8
Turni733 – 735ND:3
Helixi738 – 747ND:10
Turni748 – 750ND:3
Helixi752 – 770ND:19
Beta strandi799 – 812ND:14
Beta strandi818 – 825ND:8
Beta strandi828 – 833ND:6
Beta strandi836 – 839ND:4
Beta strandi849 – 855ND:7

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[»]
ProteinModelPortaliP45974.
SMRiP45974.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP45974.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini326 – 856USPAdd BLAST531
Domaini654 – 695UBA 1IEP:Add BLAST42
Domaini722 – 762UBA 2IEP:Add 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.IKR:

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri197 – 269UBP-typeIEP:Add BLAST73

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

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

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
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.
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

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3 – 4EL → DV in CAA62690 (PubMed:7498549).IKR:2
Sequence conflicti45I → V in CAA62690 (PubMed:7498549).IKR:1
Sequence conflicti468K → R in AAA78934 (Ref. 4) IKR:1
Sequence conflicti681G → D in AAA78934 (Ref. 4) IKR:1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005259629 – 652GSLGF…SSPTS → A in isoform Short. IBD:Add 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

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 22, 2017
This is version 182 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. Human chromosome 12
    Human chromosome 12: 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