Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1TSVAR)

• DOT Name: Mastermind-like protein 2 (MAML2)
• Synonyms: Mam-2
• Gene Name: MAML2
• Related Disease:
  Malignant soft tissue neoplasm
  Sarcoma
  T-cell acute lymphoblastic leukaemia
  Acute lymphocytic leukaemia
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Advanced cancer
  Benign neoplasm of sweat gland
  Central nervous system neoplasm
  Childhood myelodysplastic syndrome
  Epithelial ovarian cancer
  Glioma
  Juvenile idiopathic arthritis
  Lung carcinoma
  Myelodysplastic syndrome
  Schizophrenia
  Cutaneous melanoma
  Inflammatory bowel disease
  Melanoma
  Nasopharyngeal carcinoma
  Squamous cell carcinoma
  Stroke
  Adenocarcinoma
  Aplasia cutis congenita
  Clear cell adenocarcinoma
  Corpus callosum, agenesis of
  Ulcerative colitis
• UniProt ID: MAML2_HUMAN
• Pfam ID: PF09596 ; PF20804
• Sequence:
  MGDTAPPQAPAGGLGGASGAGLLGGGSVTPRVHSAIVERLRARIAVCRQHHLSCEGRYER
  GRAESSDRERESTLQLLSLVQHGQGARKAGKHTKATATAATTTAPPPPPAAPPAASQAAA
  TAAPPPPPDYHHHHQQHLLNSSNNGGSGGINGEQQPPASTPGDQRNSALIALQGSLKRKQ
  VVNLSPANSKRPNGFVDNSFLDIKRIRVGENLSAGQGGLQINNGQSQIMSGTLPMSQAPL
  RKTNTLPSHTHSPGNGLFNMGLKEVKKEPGETLSCSKHMDGQMTQENIFPNRYGDDPGEQ
  LMDPELQELFNELTNISVPPMSDLELENMINATIKQDDPFNIDLGQQSQRSTPRPSLPME
  KIVIKSEYSPGLTQGPSGSPQLRPPSAGPAFSMANSALSTSSPIPSVPQSQAQPQTGSGA
  SRALPSWQEVSHAQQLKQIAANRQQHARMQQHQQQHQPTNWSALPSSAGPSPGPFGQEKI
  PSPSFGQQTFSPQSSPMPGVAGGSGQSKVMANYMYKAGPSAQGGHLDVLMQQKPQDLSRS
  FINNPHPAMEPRQGNTKPLFHFNSDQANQQMPSVLPSQNKPSLLHYTQQQQQQQQQQQQQ
  QQQQQQQQQQQQQQQQQQQQQSSISAQQQQQQQSSISAQQQQQQQQQQQQQQQQQQQQQQ
  QQQQQPSSQPAQSLPSQPLLRSPLPLQQKLLLQQMQNQPIAGMGYQVSQQQRQDQHSVVG
  QNTGPSPSPNPCSNPNTGSGYMNSQQSLLNQQLMGKKQTLQRQIMEQKQQLLLQQQMLAD
  AEKIAPQDQINRHLSRPPPDYKDQRRNVGNMQPTAQYSGGSSTISLNSNQALANPVSTHT
  ILTPNSSLLSTSHGTRMPSLSTAVQNMGMYGNLPCNQPNTYSVTSGMNQLTQQRNPKQLL
  ANQNNPMMPRPPTLGPSNNNNVATFGAGSVGNSQQLRPNLTHSMASMPPQRTSNVMITSN
  TTAPNWASQEGTSKQQEALTSAGVRFPTGTPAAYTPNQSLQQAVGSQQFSQRAVAPPNQL
  TPAVQMRPMNQMSQTLNGQTMGPLRGLNLRPNQLSTQILPNLNQSGTGLNQSRTGINQPP
  SLTPSNFPSPNQSSRAFQGTDHSSDLAFDFLSQQNDNMGPALNSDADFIDSLLKTEPGND
  DWMKDINLDEILGNNS
• Function: Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Potentiates activation by NOTCH3 and NOTCH4 more efficiently than MAML1 or MAML3.
• Tissue Specificity: Widely expressed with high levels detected in placenta, salivary gland and skeletal muscle.
• KEGG Pathway:
  Notch sig.ling pathway (hsa04330)
  Th1 and Th2 cell differentiation (hsa04658)
  Human papillomavirus infection (hsa05165)
• Reactome Pathway:
  Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells (R-HSA-210744)
  NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947)
  NOTCH2 intracellular domain regulates transcription (R-HSA-2197563)
  Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606)
  Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862)
  Notch-HLH transcription pathway (R-HSA-350054)
  RUNX3 regulates NOTCH signaling (R-HSA-8941856)
  NOTCH3 Intracellular Domain Regulates Transcription (R-HSA-9013508)
  NOTCH4 Intracellular Domain Regulates Transcription (R-HSA-9013695)
  Formation of paraxial mesoderm (R-HSA-9793380)
  Pre-NOTCH Transcription and Translation (R-HSA-1912408)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malignant soft tissue neoplasm	DISTC6NO	Definitive	Biomarker	[1]
Sarcoma	DISZDG3U	Definitive	Biomarker	[1]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Genetic Variation	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Benign neoplasm of sweat gland	DISRJ557	Strong	Biomarker	[5]
Central nervous system neoplasm	DISFC18W	Strong	Genetic Variation	[6]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Biomarker	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[7]
Glioma	DIS5RPEH	Strong	Genetic Variation	[8]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[9]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[10]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[11]
Cutaneous melanoma	DIS3MMH9	moderate	Biomarker	[12]
Inflammatory bowel disease	DISGN23E	moderate	Genetic Variation	[13]
Melanoma	DIS1RRCY	moderate	Biomarker	[12]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Genetic Variation	[14]
Squamous cell carcinoma	DISQVIFL	moderate	Genetic Variation	[15]
Stroke	DISX6UHX	moderate	Altered Expression	[16]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[17]
Aplasia cutis congenita	DISMDAYM	Limited	Biomarker	[18]
Clear cell adenocarcinoma	DISYUGHZ	Limited	Biomarker	[19]
Corpus callosum, agenesis of	DISO9P40	Limited	Biomarker	[18]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bevacizumab	DMSD1UN	Approved	Mastermind-like protein 2 (MAML2) increases the Hypertension ADR of Bevacizumab.	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Mastermind-like protein 2 (MAML2).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mastermind-like protein 2 (MAML2).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mastermind-like protein 2 (MAML2).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Mastermind-like protein 2 (MAML2).	[24]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Mastermind-like protein 2 (MAML2).	[25]
Marinol	DM70IK5	Approved	Marinol increases the expression of Mastermind-like protein 2 (MAML2).	[27]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Mastermind-like protein 2 (MAML2).	[28]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Mastermind-like protein 2 (MAML2).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Mastermind-like protein 2 (MAML2).	[31]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Mastermind-like protein 2 (MAML2).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mastermind-like protein 2 (MAML2).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Mastermind-like protein 2 (MAML2).	[29]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Mastermind-like protein 2 (MAML2).	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mastermind-like protein 2 (MAML2).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Mastermind-like protein 2 (MAML2).	[30]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Mastermind-like protein 2 (MAML2).	[33]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Mastermind-like protein 2 (MAML2).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Mastermind-like protein 2 (MAML2).	[36]

References

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