Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1F2G4J)

• DOT Name: Protein S100-A1 (S100A1)
• Synonyms: S-100 protein alpha chain; S-100 protein subunit alpha; S100 calcium-binding protein A1
• Gene Name: S100A1
• Related Disease:
  Esophageal squamous cell carcinoma
  Psoriasis
  Type-1/2 diabetes
  Urinary bladder neoplasm
  Acinar cell carcinoma
  Adenocarcinoma
  Adult glioblastoma
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Cardiomyopathy
  Clear cell renal carcinoma
  Epithelial ovarian cancer
  Glioblastoma multiforme
  H syndrome
  Malignant peripheral nerve sheath tumor
  Meningioma
  Metastatic malignant neoplasm
  Metastatic melanoma
  Non-small-cell lung cancer
  Osteoarthritis
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Renal cell carcinoma
  Rheumatoid arthritis
  Sarcoma
  Soft tissue sarcoma
  Squamous cell carcinoma
  Vasospasm
  T-cell lymphoma
  Cardiac failure
  Congestive heart failure
  Prostate cancer
  Alzheimer disease
  Cardiovascular disease
  Depression
  Gastric cancer
  Neuroblastoma
  Stomach cancer
• UniProt ID: S10A1_HUMAN
• PDB ID: 2L0P; 2LHL; 2LLS; 2LLT; 2LLU; 2LP2; 2LP3; 2LUX; 2M3W; 5K89
• Pfam ID: PF00036 ; PF01023
• Sequence:
  MGSELETAMETLINVFHAHSGKEGDKYKLSKKELKELLQTELSGFLDAQKDVDAVDKVMK
  ELDENGDGEVDFQEYVVLVAALTVACNNFFWENS
• Function: Small calcium binding protein that plays important roles in several biological processes such as Ca(2+) homeostasis, chondrocyte biology and cardiomyocyte regulation. In response to an increase in intracellular Ca(2+) levels, binds calcium which triggers conformational changes. These changes allow interactions with specific target proteins and modulate their activity. Regulates a network in cardiomyocytes controlling sarcoplasmic reticulum Ca(2+) cycling and mitochondrial function through interaction with the ryanodine receptors RYR1 and RYR2, sarcoplasmic reticulum Ca(2+)-ATPase/ATP2A2 and mitochondrial F1-ATPase. Facilitates diastolic Ca(2+) dissociation and myofilament mechanics in order to improve relaxation during diastole.
• Tissue Specificity: Highly prevalent in heart . Also found in lesser quantities in skeletal muscle and brain .
• Reactome Pathway:
  MyD88 (R-HSA-166058)
  MyD88 deficiency (TLR2/4) (R-HSA-5602498)
  IRAK4 deficiency (TLR2/4) (R-HSA-5603041)
  Regulation of TLR by endogenous ligand (R-HSA-5686938)
  ER-Phagosome pathway (R-HSA-1236974)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Altered Expression	[1]
Psoriasis	DIS59VMN	Definitive	Genetic Variation	[2]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Definitive	Altered Expression	[4]
Acinar cell carcinoma	DIS37Y0J	Strong	Altered Expression	[5]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[6]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[7]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[8]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[9]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Cardiomyopathy	DISUPZRG	Strong	Altered Expression	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[13]
H syndrome	DISQ2RNS	Strong	Biomarker	[14]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[15]
Meningioma	DISPT4TG	Strong	Biomarker	[16]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[17]
Metastatic melanoma	DISSL43L	Strong	Genetic Variation	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[19]
Osteoarthritis	DIS05URM	Strong	Biomarker	[20]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[12]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[12]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[21]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[22]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[23]
Sarcoma	DISZDG3U	Strong	Biomarker	[24]
Soft tissue sarcoma	DISSN8XB	Strong	Genetic Variation	[25]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[26]
Vasospasm	DIS532UM	Strong	Biomarker	[27]
T-cell lymphoma	DISSXRTQ	moderate	Biomarker	[28]
Cardiac failure	DISDC067	Disputed	Biomarker	[29]
Congestive heart failure	DIS32MEA	Disputed	Biomarker	[29]
Prostate cancer	DISF190Y	Disputed	Altered Expression	[30]
Alzheimer disease	DISF8S70	Limited	Biomarker	[31]
Cardiovascular disease	DIS2IQDX	Limited	Genetic Variation	[8]
Depression	DIS3XJ69	Limited	Biomarker	[32]
Gastric cancer	DISXGOUK	Limited	Biomarker	[33]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[34]
Stomach cancer	DISKIJSX	Limited	Biomarker	[33]

16 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 Protein S100-A1 (S100A1).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein S100-A1 (S100A1).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein S100-A1 (S100A1).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein S100-A1 (S100A1).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein S100-A1 (S100A1).	[39]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein S100-A1 (S100A1).	[40]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein S100-A1 (S100A1).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein S100-A1 (S100A1).	[42]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Protein S100-A1 (S100A1).	[36]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Protein S100-A1 (S100A1).	[43]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Protein S100-A1 (S100A1).	[44]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Protein S100-A1 (S100A1).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein S100-A1 (S100A1).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein S100-A1 (S100A1).	[46]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Protein S100-A1 (S100A1).	[47]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Protein S100-A1 (S100A1).	[36]

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