Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1WM75A)

• DOT Name: Protein-glucosylgalactosylhydroxylysine glucosidase (PGGHG)
• Synonyms: EC 3.2.1.107; Acid trehalase-like protein 1
• Gene Name: PGGHG
• UniProt ID: PGGHG_HUMAN
• EC Number: 3.2.1.107
• Pfam ID: PF03632
• Sequence:
  MEDAGEDPTTFAAHSLPSDPRLLATVTNAYLGTRVFHDTLHVSGVYNGAGGDTHRAMLPS
  PLNVRLEAPAGMGEQLTETFALDTNTGSFLHTLEGPRFRASQCIYAHRTLPHVLAFRVSI
  ARLAPGSGPITLLLRSAFSPESPDLDLHQGPDFQGARYLYGHTLTPEQPGGPQQEVHMLW
  TPAPPDLTLGEGEEARTWDFLTAVGGSQAEAQACLTEALQLQARGALYTAHAQAWAQLWV
  ECGLDVVGPLQLRQALRGSLYYLLSALPQPKAPGYICHGLSPGGLSNGSREECYWGHVFW
  DQDLWMFPSILMFHPEAARAILEYRIRTLDGALENAQNLGYQGAKFAWESADSGLEVCPE
  DIYGVQEVHVNGAVVLAFELYYHTTQDLQLFREAGGWDVVRAVAEFWCSRVEWSPREEKY
  HLRGVMSPDEYHSGVNNSVYTNVLVQNSLRFAAALAQDLGLPIPSQWLAVADKIKVPFDV
  EQNFHPEFDGYEPGEVVKQADVVLLGYPVPFSLSPDVRRKNLEIYEAVTSPQGPAMTWSM
  FAVGWMELKDAVRARGLLDRSFANMAEPFKVWTENADGSGAVNFLTGMGGFLQAVVFGCT
  GFRVTRAGVTFDPVCLSGISRVSVSGIFYQGNKLNFSFSEDSVTVEVTARAGPWAPHLEA
  ELWPSQSRLSLLPGHKVSFPRSAGRIQMSPPKLPGSSSSEFPGRTFSDVRDPLQSPLWVT
  LGSSSPTESLTVDPASE
• Function: Catalyzes the hydrolysis of glucose from the disaccharide unit linked to hydroxylysine residues of collagen and collagen-like proteins.
• BioCyc Pathway: MetaCyc:ENSG00000142102-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein-glucosylgalactosylhydroxylysine glucosidase (PGGHG).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein-glucosylgalactosylhydroxylysine glucosidase (PGGHG).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein-glucosylgalactosylhydroxylysine glucosidase (PGGHG).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein-glucosylgalactosylhydroxylysine glucosidase (PGGHG).	[4]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Protein-glucosylgalactosylhydroxylysine glucosidase (PGGHG).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein-glucosylgalactosylhydroxylysine glucosidase (PGGHG).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein-glucosylgalactosylhydroxylysine glucosidase (PGGHG).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein-glucosylgalactosylhydroxylysine glucosidase (PGGHG).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [3] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [4] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [5] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.