Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7YG0AY)

• DOT Name: MAGUK p55 subfamily member 4 (MPP4)
• Synonyms: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 5 protein; Discs large homolog 6
• Gene Name: MPP4
• Related Disease:
  Breast carcinoma
  Retinitis pigmentosa
  Retinitis pigmentosa 26
  Schizophrenia
• UniProt ID: MPP4_HUMAN
• Pfam ID: PF00625 ; PF02828 ; PF00595
• Sequence:
  MIQSDKGADPPDKKDMKLSTATNPQNGLSQILRLVLQELSLFYGRDVNGVCLLYDLLHSP
  WLQALLKIYDCLQEFKEKKLVPATPHAQVLSYEVVELLRETPTSPEIQELRQMLQAPHFK
  ALLSAHDTIAQKDFEPLLPPLPDNIPESEEAMRIVCLVKNQQPLGATIKRHEMTGDILVA
  RIIHGGLAERSGLLYAGDKLVEVNGVSVEGLDPEQVIHILAMSRGTIMFKVVPVSDPPVN
  SQQMVYVRAMTEYWPQEDPDIPCMDAGLPFQKGDILQIVDQNDALWWQARKISDPATCAG
  LVPSNHLLKRKQREFWWSQPYQPHTCLKSTLSISMEEEDDMKIDEKCVEADEETFESEEL
  SEDKEEFVGYGQKFFIAGFRRSMRLCRRKSHLSPLHASVCCTGSCYSAVGAPYEEVVRYQ
  RRPSDKYRLIVLMGPSGVGVNELRRQLIEFNPSHFQSAVPHTTRTKKSYEMNGREYHYVS
  KETFENLIYSHRMLEYGEYKGHLYGTSVDAVQTVLVEGKICVMDLEPQDIQGVRTHELKP
  YVIFIKPSNMRCMKQSRKNAKVITDYYVDMKFKDEDLQEMENLAQRMETQFGQFFDHVIV
  NDSLHDACAQLLSAIQKAQEEPQWVPATWISSDTESQ
• Function: May play a role in retinal photoreceptors development.
• Tissue Specificity: Expressed in the retina (at protein level). Highly expressed in the retina. Lower amounts are detected in brain, testis, ARPE-19, RPE/choroid and fetal eye. Isoform 5 is retina-specific.
• KEGG Pathway: Tight junction (hsa04530)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Retinitis pigmentosa	DISCGPY8	Strong	Altered Expression	[2]
Retinitis pigmentosa 26	DISIAKQD	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of MAGUK p55 subfamily member 4 (MPP4).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of MAGUK p55 subfamily member 4 (MPP4).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of MAGUK p55 subfamily member 4 (MPP4).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of MAGUK p55 subfamily member 4 (MPP4).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of MAGUK p55 subfamily member 4 (MPP4).	[9]

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 increases the methylation of MAGUK p55 subfamily member 4 (MPP4).	[7]

References

• [1] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [2] Characterization of MPP4, a gene highly expressed in photoreceptor cells, and mutation analysis in retinitis pigmentosa.Gene. 2002 Sep 4;297(1-2):33-8. doi: 10.1016/s0378-1119(02)00872-7.
• [3] The common variants implicated in microstructural abnormality of first episode and drug-nave patients with schizophrenia.Sci Rep. 2017 Sep 18;7(1):11750. doi: 10.1038/s41598-017-10507-7.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [9] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.