Details of the Target

General Information of Target

Target ID LDTP13026
Target Name Ubiquitin carboxyl-terminal hydrolase 36 (USP36)
Gene Name USP36
Gene ID 57602
Synonyms
KIAA1453; Ubiquitin carboxyl-terminal hydrolase 36; EC 2.3.2.-; EC 3.4.19.12; Deubiquitinating enzyme 36; Ubiquitin thioesterase 36; Ubiquitin-specific-processing protease 36
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MDVKERRPYCSLTKSRREKERRYTNSSADNEECRVPTQKSYSSSETLKAFDHDSSRLLYG
NRVKDLVHREADEFTRQGQNFTLRQLGVCEPATRRGLAFCAEMGLPHRGYSISAGSDADT
ENEAVMSPEHAMRLWGRGVKSGRSSCLSSRSNSALTLTDTEHENKSDSENEQPASNQGQS
TLQPLPPSHKQHSAQHHPSITSLNRNSLTNRRNQSPAPPAALPAELQTTPESVQLQDSWV
LGSNVPLESRHFLFKTGTGTTPLFSTATPGYTMASGSVYSPPTRPLPRNTLSRSAFKFKK
SSKYCSWKCTALCAVGVSVLLAILLSYFIAMHLFGLNWQLQQTENDTFENGKVNSDTMPT
NTVSLPSGDNGKLGGFTQENNTIDSGELDIGRRAIQEIPPGIFWRSQLFIDQPQFLKFNI
SLQKDALIGVYGRKGLPPSHTQYDFVELLDGSRLIAREQRSLLETERAGRQARSVSLHEA
GFIQYLDSGIWHLAFYNDGKNAEQVSFNTIVIESVVECPRNCHGNGECVSGTCHCFPGFL
GPDCSRAACPVLCSGNGQYSKGRCLCFSGWKGTECDVPTTQCIDPQCGGRGICIMGSCAC
NSGYKGESCEEADCIDPGCSNHGVCIHGECHCSPGWGGSNCEILKTMCPDQCSGHGTYLQ
ESGSCTCDPNWTGPDCSNEICSVDCGSHGVCMGGTCRCEEGWTGPACNQRACHPRCAEHG
TCKDGKCECSQGWNGEHCTIEGCPGLCNSNGRCTLDQNGWHCVCQPGWRGAGCDVAMETL
CTDSKDNEGDGLIDCMDPDCCLQSSCQNQPYCRGLPDPQDIISQSLQSPSQQAAKSFYDR
ISFLIGSDSTHVIPGESPFNKSLASVIRGQVLTADGTPLIGVNVSFFHYPEYGYTITRQD
GMFDLVANGGASLTLVFERSPFLTQYHTVWIPWNVFYVMDTLVMKKEENDIPSCDLSGFV
RPNPIIVSSPLSTFFRSSPEDSPIIPETQVLHEETTIPGTDLKLSYLSSRAAGYKSVLKI
TMTQSIIPFNLMKVHLMVAVVGRLFQKWFPASPNLAYTFIWDKTDAYNQKVYGLSEAVVS
VGYEYESCLDLTLWEKRTAILQGYELDASNMGGWTLDKHHVLDVQNGILYKGNGENQFIS
QQPPVVSSIMGNGRRRSISCPSCNGQADGNKLLAPVALACGIDGSLYVGDFNYVRRIFPS
GNVTSVLELSSNPAHRYYLATDPVTGDLYVSDTNTRRIYRPKSLTGAKDLTKNAEVVAGT
GEQCLPFDEARCGDGGKAVEATLMSPKGMAVDKNGLIYFVDGTMIRKVDQNGIISTLLGS
NDLTSARPLTCDTSMHISQVRLEWPTDLAINPMDNSIYVLDNNVVLQITENRQVRIAAGR
PMHCQVPGVEYPVGKHAVQTTLESATAIAVSYSGVLYITETDEKKINRIRQVTTDGEISL
VAGIPSECDCKNDANCDCYQSGDGYAKDAKLSAPSSLAASPDGTLYIADLGNIRIRAVSK
NKPLLNSMNFYEVASPTDQELYIFDINGTHQYTVSLVTGDYLYNFSYSNDNDITAVTDSN
GNTLRIRRDPNRMPVRVVSPDNQVIWLTIGTNGCLKSMTAQGLELVLFTYHGNSGLLATK
SDETGWTTFFDYDSEGRLTNVTFPTGVVTNLHGDMDKAITVDIESSSREEDVSITSNLSS
IDSFYTMVQDQLRNSYQIGYDGSLRIIYASGLDSHYQTEPHVLAGTANPTVAKRNMTLPG
ENGQNLVEWRFRKEQAQGKVNVFGRKLRVNGRNLLSVDFDRTTKTEKIYDDHRKFLLRIA
YDTSGHPTLWLPSSKLMAVNVTYSSTGQIASIQRGTTSEKVDYDGQGRIVSRVFADGKTW
SYTYLEKSMVLLLHSQRQYIFEYDMWDRLSAITMPSVARHTMQTIRSIGYYRNIYNPPES
NASIITDYNEEGLLLQTAFLGTSRRVLFKYRRQTRLSEILYDSTRVSFTYDETAGVLKTV
NLQSDGFICTIRYRQIGPLIDRQIFRFSEDGMVNARFDYSYDNSFRVTSMQGVINETPLP
IDLYQFDDISGKVEQFGKFGVIYYDINQIISTAVMTYTKHFDAHGRIKEIQYEIFRSLMY
WITIQYDNMGRVTKREIKIGPFANTTKYAYEYDVDGQLQTVYLNEKIMWRYNYDLNGNLH
LLNPSNSARLTPLRYDLRDRITRLGDVQYRLDEDGFLRQRGTEIFEYSSKGLLTRVYSKG
SGWTVIYRYDGLGRRVSSKTSLGQHLQFFYADLTYPTRITHVYNHSSSEITSLYYDLQGH
LFAMEISSGDEFYIASDNTGTPLAVFSSNGLMLKQIQYTAYGEIYFDSNIDFQLVIGFHG
GLYDPLTKLIHFGERDYDILAGRWTTPDIEIWKRIGKDPAPFNLYMFRNNNPASKIHDVK
DYITDVNSWLVTFGFHLHNAIPGFPVPKFDLTEPSYELVKSQQWDDIPPIFGVQQQVARQ
AKAFLSLGKMAEVQVSRRRAGGAQSWLWFATVKSLIGKGVMLAVSQGRVQTNVLNIANED
CIKVAAVLNNAFYLENLHFTIEGKDTHYFIKTTTPESDLGTLRLTSGRKALENGINVTVS
QSTTVVNGRTRRFADVEMQFGALALHVRYGMTLDEEKARILEQARQRALARAWAREQQRV
RDGEEGARLWTEGEKRQLLSAGKVQGYDGYYVLSVEQYPELADSANNIQFLRQSEIGRR
Target Bioclass
Enzyme
Family
Peptidase C19 family
Subcellular location
Nucleus, nucleolus
Function
Deubiquitinase essential for the regulation of nucleolar structure and function. Required for cell and organism viability. Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability. Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm. Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions. Deubiquitinates SOD2, regulates SOD2 protein stability. Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins. Promotes CEP63 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability. Acts as a SUMO ligase to promote EXOSC10 sumoylation critical for the nucleolar RNA exosome function in rRNA processing. Binds to pre-rRNAs.
Uniprot ID
Q9P275
Ensemble ID
ENST00000312010.10
HGNC ID
HGNC:20062
ChEMBL ID
CHEMBL4630861

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 13 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		14.29  LDD0402  [1]
DBIA
 Probe Info  		C302(0.95)  LDD3311  [2]
BTD
 Probe Info  		C255(0.70)  LDD2117  [3]
NAIA_5
 Probe Info  		C903(20.00)  LDD2227  [4]
AHL-Pu-1
 Probe Info  		C992(2.04)  LDD0168  [5]
IA-alkyne
 Probe Info  		C93(0.00); C302(0.00)  LDD0165  [6]
IPM
 Probe Info  		N.A.  LDD0025  [7]
NAIA_4
 Probe Info  		C93(0.00); C977(0.00)  LDD2226  [4]
TFBX
 Probe Info  		N.A.  LDD0027  [7]
VSF
 Probe Info  		C645(0.00); C93(0.00)  LDD0007  [8]
Phosphinate-6
 Probe Info  		C645(0.00); C977(0.00); C638(0.00)  LDD0018  [9]
Methacrolein
 Probe Info  		N.A.  LDD0218  [10]
AOyne
 Probe Info  		13.80  LDD0443  [11]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0524  2-Cyano-N-(2-morpholin-4-yl-ethyl)-acetamide MDA-MB-231 C255(0.70)  LDD2117  [3]
 LDCM0025  4SU-RNA HEK-293T C992(2.04)  LDD0168  [5]
 LDCM0026  4SU-RNA+native RNA HEK-293T C992(2.82); C93(2.31); C1000(2.08)  LDD0169  [5]
 LDCM0215  AC10 HEK-293T C93(1.03)  LDD1508  [12]
 LDCM0270  AC15 HEK-293T C504(0.96)  LDD1513  [12]
 LDCM0277  AC18 HEK-293T C93(0.95)  LDD1516  [12]
 LDCM0279  AC2 HEK-293T C93(1.00)  LDD1518  [12]
 LDCM0283  AC23 HEK-293T C504(1.02)  LDD1522  [12]
 LDCM0284  AC24 HEK-293T C504(0.84)  LDD1523  [12]
 LDCM0286  AC26 HEK-293T C93(0.96)  LDD1525  [12]
 LDCM0292  AC31 HEK-293T C504(0.92)  LDD1531  [12]
 LDCM0293  AC32 HEK-293T C504(0.93)  LDD1532  [12]
 LDCM0295  AC34 HEK-293T C93(1.10)  LDD1534  [12]
 LDCM0300  AC39 HEK-293T C504(0.96)  LDD1539  [12]
 LDCM0302  AC40 HEK-293T C504(1.03)  LDD1541  [12]
 LDCM0304  AC42 HEK-293T C93(0.94)  LDD1543  [12]
 LDCM0309  AC47 HEK-293T C504(0.96)  LDD1548  [12]
 LDCM0310  AC48 HEK-293T C504(1.08)  LDD1549  [12]
 LDCM0313  AC50 HEK-293T C93(1.00)  LDD1552  [12]
 LDCM0318  AC55 HEK-293T C504(0.96)  LDD1557  [12]
 LDCM0319  AC56 HEK-293T C504(1.07)  LDD1558  [12]
 LDCM0321  AC58 HEK-293T C93(1.00)  LDD1560  [12]
 LDCM0327  AC63 HEK-293T C504(0.98)  LDD1566  [12]
 LDCM0328  AC64 HEK-293T C504(1.04)  LDD1567  [12]
 LDCM0334  AC7 HEK-293T C504(0.93)  LDD1568  [12]
 LDCM0345  AC8 HEK-293T C504(0.97)  LDD1569  [12]
 LDCM0275  AKOS034007705 HEK-293T C504(0.89)  LDD1514  [12]
 LDCM0156  Aniline NCI-H1299 11.53  LDD0403  [1]
 LDCM0632  CL-Sc Hep-G2 C903(20.00)  LDD2227  [4]
 LDCM0367  CL1 HEK-293T C93(0.70)  LDD1571  [12]
 LDCM0369  CL100 HEK-293T C258(1.24)  LDD1573  [12]
 LDCM0370  CL101 HEK-293T C93(0.80)  LDD1574  [12]
 LDCM0373  CL104 HEK-293T C258(1.40)  LDD1577  [12]
 LDCM0374  CL105 HEK-293T C93(0.79)  LDD1578  [12]
 LDCM0377  CL108 HEK-293T C258(1.40)  LDD1581  [12]
 LDCM0378  CL109 HEK-293T C93(0.76)  LDD1582  [12]
 LDCM0379  CL11 HEK-293T C504(1.05)  LDD1583  [12]
 LDCM0382  CL112 HEK-293T C258(1.40)  LDD1586  [12]
 LDCM0383  CL113 HEK-293T C93(0.93)  LDD1587  [12]
 LDCM0386  CL116 HEK-293T C258(1.36)  LDD1590  [12]
 LDCM0387  CL117 HEK-293T C93(0.89)  LDD1591  [12]
 LDCM0390  CL12 HEK-293T C504(1.00)  LDD1594  [12]
 LDCM0391  CL120 HEK-293T C258(1.39)  LDD1595  [12]
 LDCM0392  CL121 HEK-293T C93(0.85)  LDD1596  [12]
 LDCM0395  CL124 HEK-293T C258(1.67)  LDD1599  [12]
 LDCM0396  CL125 HEK-293T C93(0.72)  LDD1600  [12]
 LDCM0399  CL128 HEK-293T C258(1.18)  LDD1603  [12]
 LDCM0400  CL13 HEK-293T C93(0.89)  LDD1604  [12]
 LDCM0403  CL16 HEK-293T C258(1.19)  LDD1607  [12]
 LDCM0405  CL18 HEK-293T C93(1.01)  LDD1609  [12]
 LDCM0411  CL23 HEK-293T C504(1.05)  LDD1615  [12]
 LDCM0412  CL24 HEK-293T C504(0.87)  LDD1616  [12]
 LDCM0413  CL25 HEK-293T C93(0.78)  LDD1617  [12]
 LDCM0416  CL28 HEK-293T C258(1.42)  LDD1620  [12]
 LDCM0419  CL30 HEK-293T C93(1.18)  LDD1623  [12]
 LDCM0424  CL35 HEK-293T C504(1.11)  LDD1628  [12]
 LDCM0425  CL36 HEK-293T C504(1.13)  LDD1629  [12]
 LDCM0426  CL37 HEK-293T C93(0.80)  LDD1630  [12]
 LDCM0429  CL4 HEK-293T C258(1.07)  LDD1633  [12]
 LDCM0430  CL40 HEK-293T C258(1.25)  LDD1634  [12]
 LDCM0432  CL42 HEK-293T C93(1.12)  LDD1636  [12]
 LDCM0437  CL47 HEK-293T C504(0.97)  LDD1641  [12]
 LDCM0438  CL48 HEK-293T C504(0.93)  LDD1642  [12]
 LDCM0439  CL49 HEK-293T C93(0.75)  LDD1643  [12]
 LDCM0443  CL52 HEK-293T C258(1.26)  LDD1646  [12]
 LDCM0445  CL54 HEK-293T C93(0.93)  LDD1648  [12]
 LDCM0450  CL59 HEK-293T C504(1.07)  LDD1653  [12]
 LDCM0451  CL6 HEK-293T C93(0.98)  LDD1654  [12]
 LDCM0452  CL60 HEK-293T C504(0.96)  LDD1655  [12]
 LDCM0453  CL61 HEK-293T C93(0.81)  LDD1656  [12]
 LDCM0456  CL64 HEK-293T C258(1.27)  LDD1659  [12]
 LDCM0458  CL66 HEK-293T C93(1.14)  LDD1661  [12]
 LDCM0464  CL71 HEK-293T C504(1.01)  LDD1667  [12]
 LDCM0465  CL72 HEK-293T C504(0.87)  LDD1668  [12]
 LDCM0466  CL73 HEK-293T C93(0.69)  LDD1669  [12]
 LDCM0469  CL76 HEK-293T C258(1.37)  LDD1672  [12]
 LDCM0471  CL78 HEK-293T C93(1.03)  LDD1674  [12]
 LDCM0477  CL83 HEK-293T C504(1.07)  LDD1680  [12]
 LDCM0478  CL84 HEK-293T C504(1.10)  LDD1681  [12]
 LDCM0479  CL85 HEK-293T C93(0.80)  LDD1682  [12]
 LDCM0482  CL88 HEK-293T C258(1.12)  LDD1685  [12]
 LDCM0485  CL90 HEK-293T C93(1.04)  LDD1688  [12]
 LDCM0490  CL95 HEK-293T C504(1.02)  LDD1693  [12]
 LDCM0491  CL96 HEK-293T C504(0.93)  LDD1694  [12]
 LDCM0492  CL97 HEK-293T C93(0.70)  LDD1695  [12]
 LDCM0625  F8 Ramos C977(1.77); C93(2.50)  LDD2187  [13]
 LDCM0573  Fragment11 Ramos C977(15.77); C93(7.00)  LDD2190  [13]
 LDCM0574  Fragment12 Ramos C977(0.65); C93(0.72)  LDD2191  [13]
 LDCM0575  Fragment13 Ramos C977(0.61); C93(1.10)  LDD2192  [13]
 LDCM0576  Fragment14 Ramos C977(0.53); C93(0.78)  LDD2193  [13]
 LDCM0579  Fragment20 Ramos C977(0.88)  LDD2194  [13]
 LDCM0580  Fragment21 Ramos C977(0.79); C93(1.06)  LDD2195  [13]
 LDCM0582  Fragment23 Ramos C93(1.29)  LDD2196  [13]
 LDCM0578  Fragment27 Ramos C977(0.80)  LDD2197  [13]
 LDCM0586  Fragment28 Ramos C977(0.84); C93(0.38)  LDD2198  [13]
 LDCM0588  Fragment30 Ramos C977(0.91); C93(1.25)  LDD2199  [13]
 LDCM0589  Fragment31 Ramos C977(0.88); C93(1.56)  LDD2200  [13]
 LDCM0468  Fragment33 Ramos C977(1.50); C93(1.18)  LDD2202  [13]
 LDCM0596  Fragment38 Ramos C977(2.10)  LDD2203  [13]
 LDCM0566  Fragment4 Ramos C977(0.93); C93(1.19)  LDD2184  [13]
 LDCM0614  Fragment56 Ramos C977(1.24); C93(1.21)  LDD2205  [13]
 LDCM0569  Fragment7 Ramos C977(1.32); C93(2.15)  LDD2186  [13]
 LDCM0571  Fragment9 Ramos C977(0.80); C93(0.92)  LDD2188  [13]
 LDCM0022  KB02 HEK-293T C93(0.90); C131(1.49); C139(1.49)  LDD1492  [12]
 LDCM0023  KB03 HEK-293T C93(1.18); C131(1.09); C139(1.09)  LDD1497  [12]
 LDCM0024  KB05 G361 C302(0.95)  LDD3311  [2]

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
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 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
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
5 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
6 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
7 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
8 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
9 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
10 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
11 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
12 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402
13 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578