Details of Drug Off-Target (DOT)

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

• DOT Name: Myocardin-related transcription factor A (MRTFA)
• Synonyms: MRTF-A; MKL/myocardin-like protein 1; Megakaryoblastic leukemia 1 protein; Megakaryocytic acute leukemia protein
• Gene Name: MRTFA
• Related Disease:
  Breast cancer
  Breast carcinoma
  Thyroid gland papillary carcinoma
  Acute megakaryoblastic leukemia
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Bacteremia
  Cervical cancer
  Cervical carcinoma
  Childhood acute megakaryoblastic leukemia
  Classic Hodgkin lymphoma
  Colitis
  Colon cancer
  Colon carcinoma
  Coronary atherosclerosis
  Coronary heart disease
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Immunodeficiency
  leukaemia
  Leukemia
  Lung squamous cell carcinoma
  Lupus
  Myocardial infarction
  Myocardial ischemia
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Pulmonary fibrosis
  Renal fibrosis
  Systemic lupus erythematosus
  Systemic sclerosis
  Uterine fibroids
  Vascular disease
  Bacterial infection
  Diabetic kidney disease
  Acute myelogenous leukaemia
  Adult glioblastoma
  Immunodeficiency 66
  Inflammatory bowel disease
  Lung cancer
  Lung carcinoma
  Melanoma
  Schizophrenia
• UniProt ID: MRTFA_HUMAN
• PDB ID: 2KVU; 2KW9
• Pfam ID: PF02755 ; PF02037
• Sequence:
  MPPLKSPAAFHEQRRSLERARTEDYLKRKIRSRPERSELVRMHILEETSAEPSLQAKQLK
  LKRARLADDLNEKIAQRPGPMELVEKNILPVESSLKEAIIVGQVNYPKVADSSSFDEDSS
  DALSPEQPASHESQGSVPSPLEARVSEPLLSATSASPTQVVSQLPMGRDSREMLFLAEQP
  PLPPPPLLPPSLTNGTTIPTAKSTPTLIKQSQPKSASEKSQRSKKAKELKPKVKKLKYHQ
  YIPPDQKQDRGAPPMDSSYAKILQQQQLFLQLQILNQQQQQHHNYQAILPAPPKSAGEAL
  GSSGTPPVRSLSTTNSSSSSGAPGPCGLARQNSTSLTGKPGALPANLDDMKVAELKQELK
  LRSLPVSGTKTELIERLRAYQDQISPVPGAPKAPAATSILHKAGEVVVAFPAARLSTGPA
  LVAAGLAPAEVVVATVASSGVVKFGSTGSTPPVSPTPSERSLLSTGDENSTPGDTFGEMV
  TSPLTQLTLQASPLQILVKEEGPRAGSCCLSPGGRAELEGRDKDQMLQEKDKQIEALTRM
  LRQKQQLVERLKLQLEQEKRAQQPAPAPAPLGTPVKQENSFSSCQLSQQPLGPAHPFNPS
  LAAPATNHIDPCAVAPGPPSVVVKQEALQPEPEPVPAPQLLLGPQGPSLIKGVAPPTLIT
  DSTGTHLVLTVTNKNADSPGLSSGSPQQPSSQPGSPAPAPSAQMDLEHPLQPLFGTPTSL
  LKKEPPGYEEAMSQQPKQQENGSSSQQMDDLFDILIQSGEISADFKEPPSLPGKEKPSPK
  TVCGSPLAAQPSPSAELPQAAPPPPGSPSLPGRLEDFLESSTGLPLLTSGHDGPEPLSLI
  DDLHSQMLSSTAILDHPPSPMDTSELHFVPEPSSTMGLDLADGHLDSMDWLELSSGGPVL
  SLAPLSTTAPSLFSTDFLDGHDLQLHWDSCL
• Function: Transcription coactivator that associates with the serum response factor (SRF) transcription factor to control expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration. The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics. MRTFA binds G-actin via its RPEL repeats, regulating activity of the MRTFA-SRF complex. Activity is also regulated by filamentous actin (F-actin) in the nucleus.
• Tissue Specificity: Ubiquitously expressed, has been detected in lung, placenta, small intestine, liver, kidney, spleen, thymus, colon, muscle, heart and brain . Expressed in peripheral blood mononuclear cells (at protein level) .
• Reactome Pathway:
  RHO GTPases Activate Formins (R-HSA-5663220)
  SUMOylation of transcription cofactors (R-HSA-3899300)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[2]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Bacteremia	DIS6N9RZ	Strong	Genetic Variation	[6]
Cervical cancer	DISFSHPF	Strong	Biomarker	[4]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[4]
Childhood acute megakaryoblastic leukemia	DIS5VZDR	Strong	Genetic Variation	[7]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[8]
Colitis	DISAF7DD	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[11]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Immunodeficiency	DIS093I0	Strong	Genetic Variation	[15]
leukaemia	DISS7D1V	Strong	Biomarker	[16]
Leukemia	DISNAKFL	Strong	Biomarker	[16]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[17]
Lupus	DISOKJWA	Strong	Biomarker	[18]
Myocardial infarction	DIS655KI	Strong	Biomarker	[19]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[19]
Pancreatic cancer	DISJC981	Strong	Biomarker	[20]
Prostate cancer	DISF190Y	Strong	Biomarker	[21]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[22]
Renal fibrosis	DISMHI3I	Strong	Altered Expression	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[18]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[23]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[24]
Vascular disease	DISVS67S	Strong	Biomarker	[25]
Bacterial infection	DIS5QJ9S	moderate	Genetic Variation	[26]
Diabetic kidney disease	DISJMWEY	moderate	Altered Expression	[27]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[28]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[29]
Immunodeficiency 66	DIS7UUBQ	Limited	Unknown	[30]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[9]
Lung cancer	DISCM4YA	Limited	Altered Expression	[31]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[31]
Melanoma	DIS1RRCY	Limited	Altered Expression	[32]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[33]

14 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 Myocardin-related transcription factor A (MRTFA).	[34]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Myocardin-related transcription factor A (MRTFA).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myocardin-related transcription factor A (MRTFA).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Myocardin-related transcription factor A (MRTFA).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Myocardin-related transcription factor A (MRTFA).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Myocardin-related transcription factor A (MRTFA).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Myocardin-related transcription factor A (MRTFA).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Myocardin-related transcription factor A (MRTFA).	[41]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Myocardin-related transcription factor A (MRTFA).	[42]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Myocardin-related transcription factor A (MRTFA).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Myocardin-related transcription factor A (MRTFA).	[44]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Myocardin-related transcription factor A (MRTFA).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Myocardin-related transcription factor A (MRTFA).	[47]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Myocardin-related transcription factor A (MRTFA).	[49]

3 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 affects the methylation of Myocardin-related transcription factor A (MRTFA).	[46]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Myocardin-related transcription factor A (MRTFA).	[48]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Myocardin-related transcription factor A (MRTFA).	[48]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid affects the localization of Myocardin-related transcription factor A (MRTFA).	[50]

References

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