Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTGYTMA)

• DTT Name: Isopeptidase T (USP5)
• Synonyms: Ubiquitin-specific-processing protease 5; Ubiquitin thioesterase 5; Ubiquitin carboxyl-terminal hydrolase 5; ISOT; Deubiquitinating enzyme 5
• Gene Name: USP5
• DTT Type: Preclinical target; [1]
• BioChemical Class: Peptidase
• UniProt ID: UBP5_HUMAN
• TTD ID: T17067
• EC Number: EC 3.4.19.12
• Sequence:
  MAELSEEALLSVLPTIRVPKAGDRVHKDECAFSFDTPESEGGLYICMNTFLGFGKQYVER
  HFNKTGQRVYLHLRRTRRPKEEDPATGTGDPPRKKPTRLAIGVEGGFDLSEEKFELDEDV
  KIVILPDYLEIARDGLGGLPDIVRDRVTSAVEALLSADSASRKQEVQAWDGEVRQVSKHA
  FSLKQLDNPARIPPCGWKCSKCDMRENLWLNLTDGSILCGRRYFDGSGGNNHAVEHYRET
  GYPLAVKLGTITPDGADVYSYDEDDMVLDPSLAEHLSHFGIDMLKMQKTDKTMTELEIDM
  NQRIGEWELIQESGVPLKPLFGPGYTGIRNLGNSCYLNSVVQVLFSIPDFQRKYVDKLEK
  IFQNAPTDPTQDFSTQVAKLGHGLLSGEYSKPVPESGDGERVPEQKEVQDGIAPRMFKAL
  IGKGHPEFSTNRQQDAQEFFLHLINMVERNCRSSENPNEVFRFLVEEKIKCLATEKVKYT
  QRVDYIMQLPVPMDAALNKEELLEYEEKKRQAEEEKMALPELVRAQVPFSSCLEAYGAPE
  QVDDFWSTALQAKSVAVKTTRFASFPDYLVIQIKKFTFGLDWVPKKLDVSIEMPEELDIS
  QLRGTGLQPGEEELPDIAPPLVTPDEPKGSLGFYGNEDEDSFCSPHFSSPTSPMLDESVI
  IQLVEMGFPMDACRKAVYYTGNSGAEAAMNWVMSHMDDPDFANPLILPGSSGPGSTSAAA
  DPPPEDCVTTIVSMGFSRDQALKALRATNNSLERAVDWIFSHIDDLDAEAAMDISEGRSA
  ADSISESVPVGPKVRDGPGKYQLFAFISHMGTSTMCGHYVCHIKKEGRWVIYNDQKVCAS
  EKPPKDLGYIYFYQRVAS
• Function: 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. Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers.
• Reactome Pathway:
  Synthesis of active ubiquitin (R-HSA-8866652)
  Ub-specific processing proteases (R-HSA-5689880)

Molecular Interaction Atlas (MIA) of This DTT

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAP-15	DMOW07D	Solid tumour/cancer	2A00-2F9Z	Preclinical	[2]
vialinin A	DM95VQ6	Inflammation	1A00-CA43.1	Preclinical	[1]

References

• [1] Vialinin A is a ubiquitin-specific peptidase inhibitor. Bioorg Med Chem Lett. 2013 Aug 1;23(15):4328-31.
• [2] The proteasome deubiquitinase inhibitor bAP15 downregulates TGF-/Smad signaling and induces apoptosis via UCHL5 inhibition in ovarian cancer. Oncotarget. 2019 Oct 15;10(57):5932-5948.