Details of Drug Off-Target (DOT)

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

• DOT Name: Geranylgeranyl transferase type-1 subunit beta (PGGT1B)
• Synonyms: EC 2.5.1.59; Geranylgeranyl transferase type I subunit beta; GGTase-I-beta; Type I protein geranyl-geranyltransferase subunit beta
• Gene Name: PGGT1B
• UniProt ID: PGTB1_HUMAN
• EC Number: 2.5.1.59
• Pfam ID: PF00432
• Sequence:
  MAATEDERLAGSGEGERLDFLRDRHVRFFQRCLQVLPERYSSLETSRLTIAFFALSGLDM
  LDSLDVVNKDDIIEWIYSLQVLPTEDRSNLNRCGFRGSSYLGIPFNPSKAPGTAHPYDSG
  HIAMTYTGLSCLVILGDDLSRVNKEACLAGLRALQLEDGSFCAVPEGSENDMRFVYCASC
  ICYMLNNWSGMDMKKAITYIRRSMSYDNGLAQGAGLESHGGSTFCGIASLCLMGKLEEVF
  SEKELNRIKRWCIMRQQNGYHGRPNKPVDTCYSFWVGATLKLLKIFQYTNFEKNRNYILS
  TQDRLVGGFAKWPDSHPDALHAYFGICGLSLMEESGICKVHPALNVSTRTSERLLDLHQS
  WKTKDSKQCSENVHIST
• Function: Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. Known substrates include RAC1, RAC2, RAP1A and RAP1B.

Molecular Interaction Atlas (MIA) of This DOT

10 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 Geranylgeranyl transferase type-1 subunit beta (PGGT1B).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Geranylgeranyl transferase type-1 subunit beta (PGGT1B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Geranylgeranyl transferase type-1 subunit beta (PGGT1B).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Geranylgeranyl transferase type-1 subunit beta (PGGT1B).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Geranylgeranyl transferase type-1 subunit beta (PGGT1B).	[5]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Geranylgeranyl transferase type-1 subunit beta (PGGT1B).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Geranylgeranyl transferase type-1 subunit beta (PGGT1B).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Geranylgeranyl transferase type-1 subunit beta (PGGT1B).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Geranylgeranyl transferase type-1 subunit beta (PGGT1B).	[8]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Geranylgeranyl transferase type-1 subunit beta (PGGT1B).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [5] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.