Details of Drug Off-Target (DOT)

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

DOT Name	GPI-anchor transamidase (PIGK)
Synonyms	GPI transamidase; EC 3.-.-.-; GPI8 homolog; hGPI8; Phosphatidylinositol-glycan biosynthesis class K protein; PIG-K
Gene Name	PIGK
Related Disease	Adult lymphoma ( ) Colorectal carcinoma ( ) Hepatocellular carcinoma ( ) Lymphoma ( ) Neoplasm ( ) Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures ( ) Pediatric lymphoma ( )
UniProt ID	GPI8_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7W72; 7WLD; 8IMX; 8IMY
EC Number	3.-.-.-
Pfam ID	PF01650
Sequence	MAVTDSLSRAATVLATVLLLSFGSVAASHIEDQAEQFFRSGHTNNWAVLVCTSRFWFNYR HVANTLSVYRSVKRLGIPDSHIVLMLADDMACNPRNPKPATVFSHKNMELNVYGDDVEVD YRSYEVTVENFLRVLTGRIPPSTPRSKRLLSDDRSNILIYMTGHGGNGFLKFQDSEEITN IELADAFEQMWQKRRYNELLFIIDTCQGASMYERFYSPNIMALASSQVGEDSLSHQPDPA IGVHLMDRYTFYVLEFLEEINPASQTNMNDLFQVCPKSLCVSTPGHRTDLFQRDPKNVLI TDFFGSVRKVEITTETIKLQQDSEIMESSYKEDQMDEKLMEPLKYAEQLPVAQIIHQKPK LKDWHPPGGFILGLWALIIMVFFKTYGIKHMKFIF
Function	Component of the GPI transamidase complex, necessary for transfer of GPI to proteins. Mediates GPI anchoring in the endoplasmic reticulum, by replacing a protein's C-terminal GPI attachment signal peptide with a pre-assembled GPI. During this transamidation reaction, the GPI transamidase forms a carbonyl intermediate with the substrate protein.
KEGG Pathway	Glycosylphosphatidylinositol (GPI)-anchor biosynthesis (hsa00563 ) Metabolic pathways (hsa01100 )
Reactome Pathway	Attachment of GPI anchor to uPAR (R-HSA-162791 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adult lymphoma	DISK8IZR	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[2]
Lymphoma	DISN6V4S	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures	DISDC3N5	Strong	Autosomal recessive	[3]
Pediatric lymphoma	DIS51BK2	Strong	Altered Expression	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of GPI-anchor transamidase (PIGK).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of GPI-anchor transamidase (PIGK).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of GPI-anchor transamidase (PIGK).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of GPI-anchor transamidase (PIGK).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GPI-anchor transamidase (PIGK).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of GPI-anchor transamidase (PIGK).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of GPI-anchor transamidase (PIGK).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of GPI-anchor transamidase (PIGK).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of GPI-anchor transamidase (PIGK).	[12]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of GPI-anchor transamidase (PIGK).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of GPI-anchor transamidase (PIGK).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of GPI-anchor transamidase (PIGK).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of GPI-anchor transamidase (PIGK).	[16]
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References

1	Profiling the expression pattern of GPI transamidase complex subunits in human cancer.Mod Pathol. 2008 Aug;21(8):979-91. doi: 10.1038/modpathol.2008.76. Epub 2008 May 16.
2	A single nucleotide polymorphism in the human PIGK gene associates with low PIGK expression in colorectal cancer patients.Int J Oncol. 2012 Oct;41(4):1405-10. doi: 10.3892/ijo.2012.1567. Epub 2012 Jul 23.
3	Bi-allelic Variants in the GPI Transamidase Subunit PIGK Cause a Neurodevelopmental Syndrome with Hypotonia, Cerebellar Atrophy, and Epilepsy. Am J Hum Genet. 2020 Apr 2;106(4):484-495. doi: 10.1016/j.ajhg.2020.03.001. Epub 2020 Mar 26.
4	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
5	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.
6	Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
7	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
8	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.
9	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
11	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
12	Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
13	Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
14	Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
15	Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
16	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.