Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGYID4C)

DOT Name Post-GPI attachment to proteins factor 6 (PGAP6)
Synonyms EC 3.1.1.4; GPI processing phospholipase A2; GPI-PLA2; Protein M83; Transmembrane protein 6; Transmembrane protein 8; Transmembrane protein 8A
Gene Name PGAP6
Related Disease
Non-alcoholic fatty liver disease ( )
UniProt ID
PGAP6_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
3.1.1.4
Pfam ID
PF12036
Sequence
MGRAGTGTGGEAVAAVVAGPLLLLLLARPPPASAGYSGKSEVGLVSEHFSQAPQRLSFYS
WYGSARLFRFRVPPDAVLLRWLLQVSRESGAACTDAEITVHFRSGAPPVINPLGTSFPDD
TAVQPSFQVGVPLSTTPRSNASVNVSHPAPGDWFVAAHLPPSSQKIELKGLAPTCAYVFQ
PELLVTRVVEISIMEPDVPLPQTLLSHPSYLKVFVPDYTRELLLELRDCVSNGSLGCPVR
LTVGPVTLPSNFQKVLTCTGAPWPCRLLLPSPPWDRWLQVTAESLVGPLGTVAFSAVAAL
TACRPRSVTIQPLLQSSQNQSFNASSGLLSPSPDHQDLGRSGRVDRSPFCLTNYPVTRED
MDVVSVHFQPLDRVSVRVCSDTPSVMRLRLNTGMDSGGSLTISLRANKTEMRNETVVVAC
VNAASPFLGFNTSLNCTTAFFQGYPLSLSAWSRRANLIIPYPETDNWYLSLQLMCPENAE
DCEQAVVHVETTLYLVPCLNDCGPYGQCLLLRRHSYLYASCSCKAGWRGWSCTDNSTAQT
VAQQRAATLLLTLSNLMFLAPIAVSVRRFFLVEASVYAYTMFFSTFYHACDQPGEAVLCI
LSYDTLQYCDFLGSGAAIWVTILCMARLKTVLKYVLFLLGTLVIAMSLQLDRRGMWNMLG
PCLFAFVIMASMWAYRCGHRRQCYPTSWQRWAFYLLPGVSMASVGIAIYTSMMTSDNYYY
THSIWHILLAGSAALLLPPPDQPAEPWACSQKFPCHYQICKNDREELYAVT
Function
Involved in the lipid remodeling steps of GPI-anchor maturation. Lipid remodeling steps consist in the generation of 2 saturated fatty chains at the sn-2 position of GPI-anchor proteins (GPI-AP). Has phospholipase A2 activity that removes an acyl-chain at the sn-2 position of GPI-anchors during the remodeling of GPI. Required for the shedding of the GPI-AP CRIPTO, but not CFC1, at the cell surface. Shedding of CRIPTO modulates Nodal signaling by allowing soluble CRIPTO to act as a Nodal coreceptor on other cells. Also indirectly involved in the translocation of RAC1 from the cytosol to the plasma membrane by maintaining the steady state amount of CAV1-enriched plasma membrane subdomains, stabilizing RAC1 at the plasma membrane. In contrast to myomaker (TMEM8C), has no fusogenic activity.
Tissue Specificity Expressed in pancreas, placenta, spleen, liver, kidney, bone marrow, peripheral blood leukocytes and tonsil.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Non-alcoholic fatty liver disease DISDG1NL Strong Genetic Variation [1]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 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 Post-GPI attachment to proteins factor 6 (PGAP6). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the methylation of Post-GPI attachment to proteins factor 6 (PGAP6). [3]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Post-GPI attachment to proteins factor 6 (PGAP6). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Post-GPI attachment to proteins factor 6 (PGAP6). [7]
------------------------------------------------------------------------------------
3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Post-GPI attachment to proteins factor 6 (PGAP6). [5]
Menadione DMSJDTY Approved Menadione affects the expression of Post-GPI attachment to proteins factor 6 (PGAP6). [6]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Post-GPI attachment to proteins factor 6 (PGAP6). [8]
------------------------------------------------------------------------------------

References

1 Association of TM6SF2 rs58542926 gene polymorphism with the risk of non-alcoholic fatty liver disease and colorectal adenoma in Chinese Han population.BMC Biochem. 2019 Feb 6;20(1):3. doi: 10.1186/s12858-019-0106-3.
2 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.
3 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
4 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
5 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.
6 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
7 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
8 Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.