Details of Drug Off-Target (DOT)

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

• DOT Name: Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2)
• Synonyms: Atrophin-1-interacting protein 1; AIP-1; Atrophin-1-interacting protein A; Membrane-associated guanylate kinase inverted 2; MAGI-2
• Gene Name: MAGI2
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Amyloidosis
  Anxiety disorder
  Benign prostatic hyperplasia
  Bipolar disorder
  Cardiovascular disease
  Cholangiocarcinoma
  Chronic kidney disease
  Coeliac disease
  Colorectal carcinoma
  Crohn disease
  Endometrial cancer
  Endometrial carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  Irritable bowel syndrome
  Lung cancer
  Lung carcinoma
  Nephropathy
  Nephrotic syndrome 15
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Steroid-resistant nephrotic syndrome
  Systemic sclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Chronic obstructive pulmonary disease
  Melanoma
  Moyamoya disease
  West syndrome
  Arteriosclerosis
  Graves disease
  Hashimoto thyroiditis
  Nephrotic syndrome
  Ulcerative colitis
  Epilepsy
• UniProt ID: MAGI2_HUMAN
• PDB ID: 1UEP; 1UEQ; 1UEW; 1UJV; 1WFV
• Pfam ID: PF00625 ; PF16663 ; PF00595 ; PF00397
• Sequence:
  MSKSLKKKSHWTSKVHESVIGRNPEGQLGFELKGGAENGQFPYLGEVKPGKVAYESGSKL
  VSEELLLEVNETPVAGLTIRDVLAVIKHCKDPLRLKCVKQGGIVDKDLRHYLNLRFQKGS
  VDHELQQIIRDNLYLRTVPCTTRPHKEGEVPGVDYIFITVEDFMELEKSGALLESGTYED
  NYYGTPKPPAEPAPLLLNVTDQILPGATPSAEGKRKRNKSVSNMEKASIEPPEEEEEERP
  VVNGNGVVVTPESSEHEDKSAGASGEMPSQPYPAPVYSQPEELKEQMDDTKPTKPEDNEE
  PDPLPDNWEMAYTEKGEVYFIDHNTKTTSWLDPRLAKKAKPPEECKENELPYGWEKIDDP
  IYGTYYVDHINRRTQFENPVLEAKRKLQQHNMPHTELGTKPLQAPGFREKPLFTRDASQL
  KGTFLSTTLKKSNMGFGFTIIGGDEPDEFLQVKSVIPDGPAAQDGKMETGDVIVYINEVC
  VLGHTHADVVKLFQSVPIGQSVNLVLCRGYPLPFDPEDPANSMVPPLAIMERPPPVMVNG
  RHNYETYLEYISRTSQSVPDITDRPPHSLHSMPTDGQLDGTYPPPVHDDNVSMASSGATQ
  AELMTLTIVKGAQGFGFTIADSPTGQRVKQILDIQGCPGLCEGDLIVEINQQNVQNLSHT
  EVVDILKDCPIGSETSLIIHRGGFFSPWKTPKPIMDRWENQGSPQTSLSAPAIPQNLPFP
  PALHRSSFPDSTEAFDPRKPDPYELYEKSRAIYESRQQVPPRTSFRMDSSGPDYKELDVH
  LRRMESGFGFRILGGDEPGQPILIGAVIAMGSADRDGRLHPGDELVYVDGIPVAGKTHRY
  VIDLMHHAARNGQVNLTVRRKVLCGGEPCPENGRSPGSVSTHHSSPRSDYATYTNSNHAA
  PSSNASPPEGFASHSLQTSDVVIHRKENEGFGFVIISSLNRPESGSTITVPHKIGRIIDG
  SPADRCAKLKVGDRILAVNGQSIINMPHADIVKLIKDAGLSVTLRIIPQEELNSPTSAPS
  SEKQSPMAQQSPLAQQSPLAQPSPATPNSPIAQPAPPQPLQLQGHENSYRSEVKARQDVK
  PDIRQPPFTDYRQPPLDYRQPPGGDYQQPPPLDYRQPPLLDYRQHSPDTRQYPLSDYRQP
  QDFDYFTVDMEKGAKGFGFSIRGGREYKMDLYVLRLAEDGPAIRNGRMRVGDQIIEINGE
  STRDMTHARAIELIKSGGRRVRLLLKRGTGQVPEYDEPAPWSSPAAAAPGLPEVGVSLDD
  GLAPFSPSHPAPPSDPSHQISPGPTWDIKREHDVRKPKELSACGQKKQRLGEQRERSASP
  QRAARPRLEEAPGGQGRPEAGRPASEARAPGLAAADAADAARAGGKEAPRAAAGSELCRR
  EGPGAAPAFAGPGGGGSGALEAEGRAGARAGPRPGPRPPGGAPARKAAVAPGPWKVPGSD
  KLPSVLKPGASAASR
• Function: Seems to act as a scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. May play a role in regulating activin-mediated signaling in neuronal cells. Enhances the ability of PTEN to suppress AKT1 activation. Plays a role in receptor-mediated clathrin-dependent endocytosis which is required for ciliogenesis.
• Tissue Specificity: Specifically expressed in brain.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  PI3K-Akt sig.ling pathway (hsa04151)
• Reactome Pathway: Nephrin family interactions (R-HSA-373753)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Amyloidosis	DISHTAI2	Strong	Genetic Variation	[2]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[3]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[4]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[5]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[6]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[7]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[8]
Coeliac disease	DISIY60C	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[11]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[12]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Irritable bowel syndrome	DIS27206	Strong	Biomarker	[9]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[15]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[15]
Nephropathy	DISXWP4P	Strong	Altered Expression	[8]
Nephrotic syndrome 15	DISS43Y1	Strong	Autosomal recessive	[16]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[18]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[12]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[12]
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[1]
Steroid-resistant nephrotic syndrome	DISVEBC9	Strong	Genetic Variation	[19]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[20]
Atherosclerosis	DISMN9J3	moderate	Altered Expression	[21]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[22]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[22]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Altered Expression	[23]
Melanoma	DIS1RRCY	moderate	Genetic Variation	[22]
Moyamoya disease	DISO62CA	moderate	Genetic Variation	[24]
West syndrome	DISLIAU9	moderate	Biomarker	[25]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[26]
Graves disease	DISU4KOQ	Limited	Genetic Variation	[27]
Hashimoto thyroiditis	DIS77CDF	Limited	Genetic Variation	[27]
Nephrotic syndrome	DISSPSC2	Limited	Biomarker	[28]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[11]
Epilepsy	DISBB28L	Refuted	Autosomal dominant	[29]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
NAPQI	DM8F5LR	Investigative	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) affects the response to substance of NAPQI.	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[30]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[34]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[39]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[40]

10 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 Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[33]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[35]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[36]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[37]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[37]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[37]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2).	[42]

References

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• [38] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
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