Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRV6ORJ)

• DOT Name: Keratinocyte-associated protein 2 (KRTCAP2)
• Synonyms: KCP-2; Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit KCP2; Oligosaccharyl transferase subunit KCP2
• Gene Name: KRTCAP2
• UniProt ID: KTAP2_HUMAN
• Pfam ID: PF09775
• Sequence:
  MVVGTGTSLALSSLLSLLLFAGMQMYSRQLASTEWLTIQGGLLGSGLFVFSLTAFNNLEN
  LVFGKGFQAKIFPEILLCLLLALFASGLIHRVCVTTCFIFSMVGLYYINKISSTLYQAAA
  PVLTPAKVTGKSKKRN
• Function: Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. May be involved in N-glycosylation of APP (amyloid-beta precursor protein). Can modulate gamma-secretase cleavage of APP by enhancing endoprotelysis of PSEN1.
• Tissue Specificity: Expressed in skin, heart, placental, liver, skeletal muscle, kidney, pancreas, keratinocytes and dermal fibroblasts.

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 Keratinocyte-associated protein 2 (KRTCAP2).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Keratinocyte-associated protein 2 (KRTCAP2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Keratinocyte-associated protein 2 (KRTCAP2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Keratinocyte-associated protein 2 (KRTCAP2).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Keratinocyte-associated protein 2 (KRTCAP2).	[5]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Keratinocyte-associated protein 2 (KRTCAP2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Keratinocyte-associated protein 2 (KRTCAP2).	[7]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Keratinocyte-associated protein 2 (KRTCAP2).	[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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] 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.
• [5] 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.
• [6] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [7] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [8] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.