Details of Drug Off-Target (DOT)

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

• DOT Name: Vitamin K-dependent protein S (PROS1)
• Gene Name: PROS1
• Related Disease:
  Hereditary thrombophilia due to congenital protein S deficiency
  Metastatic malignant neoplasm
  Thrombophilia due to protein S deficiency, autosomal dominant
  Adenocarcinoma
  Alzheimer disease
  Anxiety
  Benign prostatic hyperplasia
  Coagulation defect
  Diabetic kidney disease
  Disseminated intravascular coagulation
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Haemophilia A
  Helicoid peripapillary chorioretinal degeneration
  Hereditary chronic pancreatitis
  Huntington disease
  Juvenile idiopathic arthritis
  Lung cancer
  Lung carcinoma
  Non-insulin dependent diabetes
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Prostate adenocarcinoma
  Prostate disease
  Pyruvate carboxylase deficiency disease
  Retinitis pigmentosa
  Thrombophilia
  Thrombophilia due to protein S deficiency, autosomal recessive
  Thrombosis
  Type-1/2 diabetes
  Venous thromboembolism
  Cowden disease
  Adult respiratory distress syndrome
  Anxiety disorder
  Arteriosclerosis
  Arthritis
  Atherosclerosis
  Carcinoma
  Cardiovascular disease
  Colitis
  Depression
  Melanoma
  Metastatic prostate carcinoma
  Pachyonychia congenita 3
• UniProt ID: PROS_HUMAN
• PDB ID: 1Z6C
• Pfam ID: PF07645 ; PF14670 ; PF00594 ; PF12661 ; PF00054 ; PF02210
• Sequence:
  MRVLGGRCGALLACLLLVLPVSEANFLSKQQASQVLVRKRRANSLLEETKQGNLERECIE
  ELCNKEEAREVFENDPETDYFYPKYLVCLRSFQTGLFTAARQSTNAYPDLRSCVNAIPDQ
  CSPLPCNEDGYMSCKDGKASFTCTCKPGWQGEKCEFDINECKDPSNINGGCSQICDNTPG
  SYHCSCKNGFVMLSNKKDCKDVDECSLKPSICGTAVCKNIPGDFECECPEGYRYNLKSKS
  CEDIDECSENMCAQLCVNYPGGYTCYCDGKKGFKLAQDQKSCEVVSVCLPLNLDTKYELL
  YLAEQFAGVVLYLKFRLPEISRFSAEFDFRTYDSEGVILYAESIDHSAWLLIALRGGKIE
  VQLKNEHTSKITTGGDVINNGLWNMVSVEELEHSISIKIAKEAVMDINKPGPLFKPENGL
  LETKVYFAGFPRKVESELIKPINPRLDGCIRSWNLMKQGASGIKEIIQEKQNKHCLVTVE
  KGSYYPGSGIAQFHIDYNNVSSAEGWHVNVTLNIRPSTGTGVMLALVSGNNTVPFAVSLV
  DSTSEKSQDILLSVENTVIYRIQALSLCSDQQSHLEFRVNRNNLELSTPLKIETISHEDL
  QRQLAVLDKAMKAKVATYLGGLPDVPFSATPVNAFYNGCMEVNINGVQLDLDEAISKHND
  IRAHSCPSVWKKTKNS
• Function: Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis.
• Tissue Specificity: Plasma.
• KEGG Pathway:
  Efferocytosis (hsa04148)
  Complement and coagulation cascades (hsa04610)
• Reactome Pathway:
  Intrinsic Pathway of Fibrin Clot Formation (R-HSA-140837)
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)
  Gamma-carboxylation of protein precursors (R-HSA-159740)
  Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus (R-HSA-159763)
  Removal of aminoterminal propeptides from gamma-carboxylated proteins (R-HSA-159782)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Regulation of Complement cascade (R-HSA-977606)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary thrombophilia due to congenital protein S deficiency	DISP7RXI	Definitive	Semidominant	[1]
Metastatic malignant neoplasm	DIS86UK6	Definitive	Biomarker	[2]
Thrombophilia due to protein S deficiency, autosomal dominant	DISLW5LN	Definitive	Semidominant	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Anxiety	DISIJDBA	Strong	Biomarker	[6]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[7]
Coagulation defect	DIS9X3H6	Strong	Biomarker	[8]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[9]
Disseminated intravascular coagulation	DISCAVOZ	Strong	Biomarker	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[11]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[12]
Haemophilia A	DIS0RQ2E	Strong	Genetic Variation	[13]
Helicoid peripapillary chorioretinal degeneration	DISFSS5N	Strong	Genetic Variation	[14]
Hereditary chronic pancreatitis	DISF0J1Q	Strong	Genetic Variation	[15]
Huntington disease	DISQPLA4	Strong	Biomarker	[16]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[17]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Lung carcinoma	DISTR26C	Strong	Biomarker	[18]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[19]
Obesity	DIS47Y1K	Strong	Biomarker	[20]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[11]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[11]
Prostate adenocarcinoma	DISBZYU8	Strong	Genetic Variation	[21]
Prostate disease	DISFVG19	Strong	Biomarker	[22]
Pyruvate carboxylase deficiency disease	DIS6000W	Strong	Biomarker	[23]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[24]
Thrombophilia	DISQR7U7	Strong	Biomarker	[25]
Thrombophilia due to protein S deficiency, autosomal recessive	DISIIA6I	Strong	Autosomal recessive	[26]
Thrombosis	DIS2TXP8	Strong	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[20]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[28]
Cowden disease	DISMYKCE	moderate	Biomarker	[29]
Adult respiratory distress syndrome	DISIJV47	Limited	Biomarker	[30]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[31]
Arthritis	DIST1YEL	Limited	Biomarker	[32]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[31]
Carcinoma	DISH9F1N	Limited	Genetic Variation	[33]
Cardiovascular disease	DIS2IQDX	Limited	Biomarker	[31]
Colitis	DISAF7DD	Limited	Altered Expression	[34]
Depression	DIS3XJ69	Limited	Biomarker	[6]
Melanoma	DIS1RRCY	Limited	Altered Expression	[35]
Metastatic prostate carcinoma	DISVBEZ9	Limited	Altered Expression	[36]
Pachyonychia congenita 3	DISZLC6C	Limited	Biomarker	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Warfarin	DMJYCVW	Approved	Vitamin K-dependent protein S (PROS1) affects the response to substance of Warfarin.	[65]

29 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 Vitamin K-dependent protein S (PROS1).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Vitamin K-dependent protein S (PROS1).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Vitamin K-dependent protein S (PROS1).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Vitamin K-dependent protein S (PROS1).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Vitamin K-dependent protein S (PROS1).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Vitamin K-dependent protein S (PROS1).	[43]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Vitamin K-dependent protein S (PROS1).	[44]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Vitamin K-dependent protein S (PROS1).	[45]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Vitamin K-dependent protein S (PROS1).	[46]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Vitamin K-dependent protein S (PROS1).	[47]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Vitamin K-dependent protein S (PROS1).	[48]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Vitamin K-dependent protein S (PROS1).	[44]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Vitamin K-dependent protein S (PROS1).	[49]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Vitamin K-dependent protein S (PROS1).	[50]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Vitamin K-dependent protein S (PROS1).	[51]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate decreases the expression of Vitamin K-dependent protein S (PROS1).	[52]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Vitamin K-dependent protein S (PROS1).	[53]
Cenestin	DMXQS7K	Approved	Cenestin decreases the expression of Vitamin K-dependent protein S (PROS1).	[54]
Desogestrel	DM27U4Y	Approved	Desogestrel affects the expression of Vitamin K-dependent protein S (PROS1).	[55]
Gestodene	DM9R1YU	Phase 4	Gestodene decreases the expression of Vitamin K-dependent protein S (PROS1).	[56]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Vitamin K-dependent protein S (PROS1).	[57]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Vitamin K-dependent protein S (PROS1).	[58]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Vitamin K-dependent protein S (PROS1).	[58]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Vitamin K-dependent protein S (PROS1).	[59]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Vitamin K-dependent protein S (PROS1).	[61]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Vitamin K-dependent protein S (PROS1).	[62]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Vitamin K-dependent protein S (PROS1).	[63]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Vitamin K-dependent protein S (PROS1).	[64]
Piceatannol	DMYOP45	Investigative	Piceatannol decreases the expression of Vitamin K-dependent protein S (PROS1).	[58]

1 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 increases the methylation of Vitamin K-dependent protein S (PROS1).	[60]

References

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