Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVSYP9)

• DTT Name: Ubiquitin carboxyl-terminal hydrolase 14 (USP14)
• Synonyms: Ubiquitin-specific-processing protease 14; Ubiquitin thioesterase 14; TGT; Deubiquitinating enzyme 14
• Gene Name: USP14
• DTT Type: Preclinical target; [1]
• BioChemical Class: Peptidase
• UniProt ID: UBP14_HUMAN
• TTD ID: T14875
• EC Number: EC 3.4.19.12
• Sequence:
  MPLYSVTVKWGKEKFEGVELNTDEPPMVFKAQLFALTGVQPARQKVMVKGGTLKDDDWGN
  IKIKNGMTLLMMGSADALPEEPSAKTVFVEDMTEEQLASAMELPCGLTNLGNTCYMNATV
  QCIRSVPELKDALKRYAGALRASGEMASAQYITAALRDLFDSMDKTSSSIPPIILLQFLH
  MAFPQFAEKGEQGQYLQQDANECWIQMMRVLQQKLEAIEDDSVKETDSSSASAATPSKKK
  SLIDQFFGVEFETTMKCTESEEEEVTKGKENQLQLSCFINQEVKYLFTGLKLRLQEEITK
  QSPTLQRNALYIKSSKISRLPAYLTIQMVRFFYKEKESVNAKVLKDVKFPLMLDMYELCT
  PELQEKMVSFRSKFKDLEDKKVNQQPNTSDKKSSPQKEVKYEPFSFADDIGSNNCGYYDL
  QAVLTHQGRSSSSGHYVSWVKRKQDEWIKFDDDKVSIVTPEDILRLSGGGDWHIAYVLLY
  GPRRVEIMEEESEQ
• Function: Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation. Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins.
• Reactome Pathway: Ub-specific processing proteases (R-HSA-5689880)

Molecular Interaction Atlas (MIA) of This DTT

2 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID26077642-Compound-Figure3A	DMENX90	N. A.	N. A.	Patented	[1]
Tricyclic heterocycle derivative 4	DM9XBL4	N. A.	N. A.	Patented	[1]

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]
IU1	DMJ0A2R	Neurodegenerative disorder	8A20-8A23	Preclinical	[3]

References

• [1] Deubiquitinases (DUBs) and DUB inhibitors: a patent review.Expert Opin Ther Pat. 2015;25(10):1191-1208.
• [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.
• [3] Neurotoxic mechanisms by which the USP14 inhibitor IU1 depletes ubiquitinated proteins and Tau in rat cerebral cortical neurons: Relevance to Alzheimer's disease. Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1157-1170.