Details of the Target

General Information of Target

Target ID LDTP03707
Target Name Ubiquitin carboxyl-terminal hydrolase 6 (USP6)
Gene Name USP6
Gene ID 9098
Synonyms
HRP1; TRE2; Ubiquitin carboxyl-terminal hydrolase 6; EC 3.4.19.12; Deubiquitinating enzyme 6; Proto-oncogene TRE-2; RN-tre; Ubiquitin thioesterase 6; Ubiquitin-specific-processing protease 6
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDMVENADSLQAQERKDILMKYDKGHRAGLPEDKGPEPVGINSSIDRFGILHETELPPVT
AREAKKIRREMTRTSKWMEMLGEWETYKHSSKLIDRVYKGIPMNIRGPVWSVLLNIQEIK
LKNPGRYQIMKERGKRSSEHIHHIDLDVRTTLRNHVFFRDRYGAKQRELFYILLAYSEYN
PEVGYCRDLSHITALFLLYLPEEDAFWALVQLLASERHSLPGFHSPNGGTVQGLQDQQEH
VVPKSQPKTMWHQDKEGLCGQCASLGCLLRNLIDGISLGLTLRLWDVYLVEGEQVLMPIT
SIALKVQQKRLMKTSRCGLWARLRNQFFDTWAMNDDTVLKHLRASTKKLTRKQGDLPPPA
KREQGSLAPRPVPASRGGKTLCKGYRQAPPGPPAQFQRPICSASPPWASRFSTPCPGGAV
REDTYPVGTQGVPSLALAQGGPQGSWRFLEWKSMPRLPTDLDIGGPWFPHYDFEWSCWVR
AISQEDQLATCWQAEHCGEVHNKDMSWPEEMSFTANSSKIDRQKVPTEKGATGLSNLGNT
CFMNSSIQCVSNTQPLTQYFISGRHLYELNRTNPIGMKGHMAKCYGDLVQELWSGTQKSV
APLKLRRTIAKYAPKFDGFQQQDSQELLAFLLDGLHEDLNRVHEKPYVELKDSDGRPDWE
VAAEAWDNHLRRNRSIIVDLFHGQLRSQVKCKTCGHISVRFDPFNFLSLPLPMDSYMDLE
ITVIKLDGTTPVRYGLRLNMDEKYTGLKKQLRDLCGLNSEQILLAEVHDSNIKNFPQDNQ
KVQLSVSGFLCAFEIPVPSSPISASSPTQIDFSSSPSTNGMFTLTTNGDLPKPIFIPNGM
PNTVVPCGTEKNFTNGMVNGHMPSLPDSPFTGYIIAVHRKMMRTELYFLSPQENRPSLFG
MPLIVPCTVHTRKKDLYDAVWIQVSWLARPLPPQEASIHAQDRDNCMGYQYPFTLRVVQK
DGNSCAWCPQYRFCRGCKIDCGEDRAFIGNAYIAVDWHPTALHLRYQTSQERVVDKHESV
EQSRRAQAEPINLDSCLRAFTSEEELGESEMYYCSKCKTHCLATKKLDLWRLPPFLIIHL
KRFQFVNDQWIKSQKIVRFLRESFDPSAFLVPRDPALCQHKPLTPQGDELSKPRILAREV
KKVDAQSSAGKEDMLLSKSPSSLSANISSSPKGSPSSSRKSGTSCPSSKNSSPNSSPRTL
GRSKGRLRLPQIGSKNKPSSSKKNLDASKENGAGQICELADALSRGHMRGGSQPELVTPQ
DHEVALANGFLYEHEACGNGCGDGYSNGQLGNHSEEDSTDDQREDTHIKPIYNLYAISCH
SGILSGGHYITYAKNPNCKWYCYNDSSCEELHPDEIDTDSAYILFYEQQGIDYAQFLPKI
DGKKMADTSSTDEDSESDYEKYSMLQ
Target Bioclass
Enzyme
Family
Peptidase C19 family
Subcellular location
Cell membrane
Function
Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyzes its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity. Promotes plasma membrane localization of ARF6 and selectively regulates ARF6-dependent endocytic protein trafficking. Is able to initiate tumorigenesis by inducing the production of matrix metalloproteinases following NF-kappa-B activation. May act as a GTPase-activating protein for RAB3A.
Uniprot ID
P35125
Ensemble ID
ENST00000250066.6
HGNC ID
HGNC:12629
ChEMBL ID
CHEMBL4630817

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A549 SNV: p.P31T .
BXPC3 SNV: p.K131R .
CAL51 Deletion: p.H470IfsTer36 DBIA    Probe Info 
COLO792 SNV: p.P526S .
HCT15 SNV: p.W478Ter .
IGROV1 SNV: p.G428D DBIA    Probe Info 
Ishikawa (Heraklio) 02 ER SNV: p.M947T .
KYSE410 SNV: p.Y1053C .
MCC13 SNV: p.D741N .
MEWO SNV: p.P863S; p.F870S; p.E1355K DBIA    Probe Info 
MKN45 SNV: p.V1143M DBIA    Probe Info 
MOLT4 Deletion: p.L707CfsTer13 IA-alkyne    Probe Info 
NCIH1155 SNV: p.C1348Y DBIA    Probe Info 
NCIH1944 SNV: p.S1347R DBIA    Probe Info 
NUGC3 SNV: p.K66N DBIA    Probe Info 
OVTOKO Deletion: p.K1058TfsTer22
Insertion: p.C1061LfsTer21		 .
OZ SNV: p.T86K DBIA    Probe Info 
RKO Insertion: p.S1252AfsTer14 .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IPM
 Probe Info  		N.A.  LDD0241  [1]
DBIA
 Probe Info  		C868(2.05)  LDD3310  [2]
IA-alkyne
 Probe Info  		N.A.  LDD0162  [3]
NAIA_5
 Probe Info  		C1237(0.00); C1036(0.00); C1061(0.00)  LDD2223  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 769-P C868(2.20)  LDD2246  [2]
 LDCM0023  KB03 769-P C868(2.03)  LDD2663  [2]
 LDCM0024  KB05 COLO792 C868(2.05)  LDD3310  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MYL2) . P10916
Serine/threonine-protein phosphatase 6 regulatory ankyrin repeat subunit B (ANKRD44) . Q8N8A2

References

1 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
2 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
3 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
4 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264