Details of Drug Off-Target (DOT)

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

• DOT Name: G-protein coupled receptor-associated sorting protein 1 (GPRASP1)
• Synonyms: GASP-1
• Gene Name: GPRASP1
• Related Disease:
  Asthma
  Gonorrhea
• UniProt ID: GASP1_HUMAN
• Pfam ID: PF04826
• Sequence:
  MTGAEIESGAQVKPEKKPGEEVVGGAEIENDVPLVVRPKVRTQAQIMPGARPKNKSKVMP
  GASTKVETSAVGGARPKSKAKAIPVSRFKEEAQMWAQPRFGAERLSKTERNSQTNIIASP
  LVSTDSVLVAKTKYLSEDRELVNTDTESFPRRKAHYQAGFQPSFRSKEETNMGSWCCPRP
  TSKQEASPNSDFKWVDKSVSSLFWSGDEVTAKFHPGNRVKDSNRSMHMANQEANTMSRSQ
  TNQELYIASSSGSEDESVKTPWFWARDKTNTWSGPREDPNSRSRFRSKKEVYVESSSGSE
  HEDHLESWFGAGKEAKFRSKMRAGKEANNRARHRAKREACIDFMPGSIDVIKKESCFWPE
  ENANTFSRPMIKKEARARAMTKEEAKTKARARAKQEARSEEEALIGTWFWATDESSMADE
  ASIESSLQVEDESIIGSWFWTEEEASMGTGASSKSRPRTDGERIGDSLFGAREKTSMKTG
  AEATSESILAADDEQVIIGSWFWAGEEVNQEAEEETIFGSWFWVIDAASVESGVGVSCES
  RTRSEEEEVIGPWFWSGEQVDIEAGIGEEARPGAEEETIFGSWFWAENQTYMDCRAETSC
  DTMQGAEEEEPIIGSWFWTRVEACVEGDVNSKSSLEDKEEAMIPCFGAKEEVSMKHGTGV
  RCRFMAGAEETNNKSCFWAEKEPCMYPAGGGSWKSRPEEEEDIVNSWFWSRKYTKPEAII
  GSWLWATEESNIDGTGEKAKLLTEEETIINSWFWKEDEAISEATDREESRPEAEEGDIIG
  SWFWAGEEDRLEPAAETREEDRLAAEKEGIVGSWFGAREETIRREAGSCSKSSPKAEEEE
  VIIGSWFWEEEASPEAVAGVGFESKPGTEEEEITVGSWFWPEEEASIQAGSQAVEEMESE
  TEEETIFGSWFWDGKEVSEEAGPCCVSKPEDDEEMIVESWFWSRDKAIKETGTVATCESK
  PENEEGAIVGSWFEAEDEVDNRTDNGSNCGSRTLADEDEAIVGSWFWAGDEAHFESNPSP
  VFRAICRSTCSVEQEPDPSRRPQSWEEVTVQFKPGPWGRVGFPSISPFRFPKEAASLFCE
  MFGGKPRNMVLSPEGEDQESLLQPDQPSPEFPFQYDPSYRSVQEIREHLRAKESTEPESS
  SCNCIQCELKIGSEEFEELLLLMEKIRDPFIHEISKIAMGMRSASQFTRDFIRDSGVVSL
  IETLLNYPSSRVRTSFLENMIRMAPPYPNLNIIQTYICKVCEETLAYSVDSPEQLSGIRM
  IRHLTTTTDYHTLVANYMSGFLSLLATGNAKTRFHVLKMLLNLSENLFMTKELLSAEAVS
  EFIGLFNREETNDNIQIVLAIFENIGNNIKKETVFSDDDFNIEPLISAFHKVEKFAKELQ
  GKTDNQNDPEGDQEN
• Function: Modulates lysosomal sorting and functional down-regulation of a variety of G-protein coupled receptors. Targets receptors for degradation in lysosomes via its interaction with BECN2.
• Tissue Specificity: Expressed in the brain, with lower expression in medulla, spinal cord and substantia nigra.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Disputed	Biomarker	[1]
Gonorrhea	DISQ5AO6	Limited	Biomarker	[2]

4 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 G-protein coupled receptor-associated sorting protein 1 (GPRASP1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of G-protein coupled receptor-associated sorting protein 1 (GPRASP1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of G-protein coupled receptor-associated sorting protein 1 (GPRASP1).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of G-protein coupled receptor-associated sorting protein 1 (GPRASP1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of G-protein coupled receptor-associated sorting protein 1 (GPRASP1).	[6]

References

• [1] Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study.Lancet Respir Med. 2019 Jan;7(1):20-34. doi: 10.1016/S2213-2600(18)30389-8. Epub 2018 Dec 11.
• [2] Summary and Trends of the Russian Gonococcal Antimicrobial Surveillance Programme, 2005 to 2016.J Clin Microbiol. 2019 May 24;57(6):e02024-18. doi: 10.1128/JCM.02024-18. Print 2019 Jun.
• [3] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] 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.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.