Details of Drug Off-Target (DOT)

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

• DOT Name: Mothers against decapentaplegic homolog 5 (SMAD5)
• Synonyms: MAD homolog 5; Mothers against DPP homolog 5; JV5-1; SMAD family member 5; SMAD 5; Smad5; hSmad5
• Gene Name: SMAD5
• Related Disease:
  Colitis
  Crohn disease
  Inflammatory bowel disease
  Neoplasm
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Adult lymphoma
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Diabetic kidney disease
  Esophageal cancer
  Granulosa cell tumor
  Juvenile polyposis syndrome
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Lung neoplasm
  Lymphoma
  Myelodysplastic syndrome
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Osteoporosis
  Pediatric lymphoma
  Plasma cell myeloma
  Hepatocellular carcinoma
  Schizophrenia
  Chronic pancreatitis
  Cocaine addiction
  Myeloid neoplasm
  Non-insulin dependent diabetes
  Substance withdrawal syndrome
• UniProt ID: SMAD5_HUMAN
• PDB ID: 6FZS; 6TCE
• Pfam ID: PF03165 ; PF03166
• Sequence:
  MTSMASLFSFTSPAVKRLLGWKQGDEEEKWAEKAVDALVKKLKKKKGAMEELEKALSSPG
  QPSKCVTIPRSLDGRLQVSHRKGLPHVIYCRVWRWPDLQSHHELKPLDICEFPFGSKQKE
  VCINPYHYKRVESPVLPPVLVPRHNEFNPQHSLLVQFRNLSHNEPHMPQNATFPDSFHQP
  NNTPFPLSPNSPYPPSPASSTYPNSPASSGPGSPFQLPADTPPPAYMPPDDQMGQDNSQP
  MDTSNNMIPQIMPSISSRDVQPVAYEEPKHWCSIVYYELNNRVGEAFHASSTSVLVDGFT
  DPSNNKSRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECLSDSSIFVQSRNC
  NFHHGFHPTTVCKIPSSCSLKIFNNQEFAQLLAQSVNHGFEAVYELTKMCTIRMSFVKGW
  GAEYHRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPLNPISSVS
• Function: Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis. Upon BMP ligand binding to their receptors at the cell surface, is phosphorylated by activated type I BMP receptors (BMPRIs) and associates with SMAD4 to form an heteromeric complex which translocates into the nucleus acting as transcription factor. In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network. Non-phosphorylated SMAD5 has a cytoplasmic role in energy metabolism regulation by promoting mitochondrial respiration and glycolysis in response to cytoplasmic pH changes. Mechanistically, interacts with hexokinase 1/HK1 and thereby accelerates glycolysis.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  TGF-beta sig.ling pathway (hsa04350)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway: Signaling by BMP (R-HSA-201451)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colitis	DISAF7DD	Definitive	Biomarker	[1]
Crohn disease	DIS2C5Q8	Definitive	Altered Expression	[1]
Inflammatory bowel disease	DISGN23E	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Definitive	Posttranslational Modification	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[3]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[4]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[6]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[7]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[6]
Granulosa cell tumor	DISKWVAB	Strong	Altered Expression	[8]
Juvenile polyposis syndrome	DISBPSLH	Strong	Genetic Variation	[9]
leukaemia	DISS7D1V	Strong	Biomarker	[10]
Leukemia	DISNAKFL	Strong	Biomarker	[10]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[11]
Lung neoplasm	DISVARNB	Strong	Biomarker	[12]
Lymphoma	DISN6V4S	Strong	Biomarker	[4]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[10]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[13]
Osteoporosis	DISF2JE0	Strong	Biomarker	[14]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[4]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[16]
Schizophrenia	DISSRV2N	moderate	Altered Expression	[17]
Chronic pancreatitis	DISBUOMJ	Limited	Biomarker	[18]
Cocaine addiction	DISHTRXG	Limited	Biomarker	[19]
Myeloid neoplasm	DIS2YOWO	Limited	Biomarker	[20]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Therapeutic	[21]
Substance withdrawal syndrome	DISTT24U	Limited	Biomarker	[19]

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 Mothers against decapentaplegic homolog 5 (SMAD5).	[22]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the phosphorylation of Mothers against decapentaplegic homolog 5 (SMAD5).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Mothers against decapentaplegic homolog 5 (SMAD5).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Mothers against decapentaplegic homolog 5 (SMAD5).	[36]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Mothers against decapentaplegic homolog 5 (SMAD5).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[23]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[25]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[26]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[27]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[28]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[29]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[30]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[31]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[33]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[38]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Mothers against decapentaplegic homolog 5 (SMAD5).	[39]

References

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