Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9EDIG7)

• DOT Name: Proteasomal ATPase-associated factor 1 (PAAF1)
• Synonyms: Protein G-16; WD repeat-containing protein 71
• Gene Name: PAAF1
• UniProt ID: PAAF1_HUMAN
• Pfam ID: PF00400
• Sequence:
  MAAPLRIQSDWAQALRKDEGEAWLSCHPPGKPSLYGSLTCQGIGLDGIPEVTASEGFTVN
  EINKKSIHISCPKENASSKFLAPYTTFSRIHTKSITCLDISSRGGLGVSSSTDGTMKIWQ
  ASNGELRRVLEGHVFDVNCCRFFPSGLVVLSGGMDAQLKIWSAEDASCVVTFKGHKGGIL
  DTAIVDRGRNVVSASRDGTARLWDCGRSACLGVLADCGSSINGVAVGAADNSINLGSPEQ
  MPSEREVGTEAKMLLLAREDKKLQCLGLQSRQLVFLFIGSDAFNCCTFLSGFLLLAGTQD
  GNIYQLDVRSPRAPVQVIHRSGAPVLSLLSVRDGFIASQGDGSCFIVQQDLDYVTELTGA
  DCDPVYKVATWEKQIYTCCRDGLVRRYQLSDL
• Function: Inhibits proteasome 26S assembly and proteolytic activity by impairing the association of the 19S regulatory complex with the 20S core. In case of HIV-1 infection, recruited by viral Tat to the HIV-1 promoter, where it promotes the recruitment of 19S regulatory complex through dissociation of the proteasome 26S. This presumably promotes provirus transcription efficiency. Protects SUPT6H from proteasomal degradation.
• Tissue Specificity: Ubiquitously expressed, with highest levels in kidney, brain and testis.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Proteasomal ATPase-associated factor 1 (PAAF1) affects the response to substance of Acetaminophen.	[5]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Proteasomal ATPase-associated factor 1 (PAAF1).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Proteasomal ATPase-associated factor 1 (PAAF1).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Proteasomal ATPase-associated factor 1 (PAAF1).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Proteasomal ATPase-associated factor 1 (PAAF1).	[4]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [5] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.