Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGY9B5T)

• DOT Name: Phospholipid scramblase 1 (PLSCR1)
• Synonyms: PL scramblase 1; Ca(2+)-dependent phospholipid scramblase 1; Erythrocyte phospholipid scramblase; Mg(2+)-dependent nuclease; EC 3.1.-.-; MmTRA1b
• Gene Name: PLSCR1
• Related Disease:
  Cerebral infarction
  Colorectal carcinoma
  Acute myelogenous leukaemia
  Acute myelomonocytic leukemia M4
  Cervical cancer
  Cervical carcinoma
  Chromosomal disorder
  Hepatitis B virus infection
  Influenza
  Mantle cell lymphoma
  Myeloid leukaemia
  Promyelocytic leukaemia
  Systemic lupus erythematosus
  Thrombophilia
  Autoimmune polyendocrinopathy
  Nasopharyngeal carcinoma
  Neoplasm
  Phospholipid syndrome
• UniProt ID: PLS1_HUMAN
• PDB ID: 1Y2A
• EC Number: 3.1.-.-
• Pfam ID: PF03803
• Sequence:
  MDKQNSQMNASHPETNLPVGYPPQYPPTAFQGPPGYSGYPGPQVSYPPPPAGHSGPGPAG
  FPVPNQPVYNQPVYNQPVGAAGVPWMPAPQPPLNCPPGLEYLSQIDQILIHQQIELLEVL
  TGFETNNKYEIKNSFGQRVYFAAEDTDCCTRNCCGPSRPFTLRIIDNMGQEVITLERPLR
  CSSCCCPCCLQEIEIQAPPGVPIGYVIQTWHPCLPKFTIQNEKREDVLKISGPCVVCSCC
  GDVDFEIKSLDEQCVVGKISKHWTGILREAFTDADNFGIQFPLDLDVKMKAVMIGACFLI
  DFMFFESTGSQEQKSGVW
• Function: Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer leaflet of the plasma membrane resulting in collapse of the phospholipid asymmetry which leads to phosphatidylserine externalization on the cell surface. Mediates calcium-dependent phosphatidylserine externalization and apoptosis in neurons via its association with TRPC5. Also exhibits magnesium-dependent nuclease activity against double-stranded DNA and RNA but not single-stranded DNA and can enhance DNA decatenation mediated by TOP2A. Negatively regulates FcR-mediated phagocytosis in differentiated macrophages. May contribute to cytokine-regulated cell proliferation and differentiation. May play a role in the antiviral response of interferon (IFN) by amplifying and enhancing the IFN response through increased expression of select subset of potent antiviral genes. Inhibits the functions of viral transactivators, including human T-cell leukemia virus (HTLV)-1 protein Tax, human immunodeficiency virus (HIV)-1 Tat, human hepatitis B virus (HBV) HBx, Epstein-Barr virus (EBV) BZLF1 and human cytomegalovirus IE1 and IE2 proteins through direct interactions. Mediates also the inhibition of influenza virus infection by preventing nuclear import of the viral nucleoprotein/NP. Plays a crucial role as a defense factor against SARS-CoV-2 independently of its scramblase activity by directly targeting nascent viral vesicles to prevent virus-membrane fusion and the release of viral RNA into the host-cell cytosol ; (Microbial infection) Acts as an attachment receptor for HCV.
• Tissue Specificity: Expressed in platelets, erythrocyte membranes, lymphocytes, spleen, thymus, prostate, testis, uterus, intestine, colon, heart, placenta, lung, liver, kidney and pancreas. Not detected in brain and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebral infarction	DISR1WNP	Definitive	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Definitive	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[3]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Altered Expression	[4]
Cervical cancer	DISFSHPF	Strong	Biomarker	[5]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[5]
Chromosomal disorder	DISM5BB5	Strong	Altered Expression	[4]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[6]
Influenza	DIS3PNU3	Strong	Altered Expression	[7]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[8]
Myeloid leukaemia	DISMN944	Strong	Altered Expression	[9]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[9]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[10]
Thrombophilia	DISQR7U7	Strong	Altered Expression	[10]
Autoimmune polyendocrinopathy	DISOLDB2	Limited	Altered Expression	[11]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[12]
Neoplasm	DISZKGEW	Limited	Altered Expression	[13]
Phospholipid syndrome	DISPI49U	Limited	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Phospholipid scramblase 1 (PLSCR1) affects the response to substance of Fluorouracil.	[37]

1 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 Phospholipid scramblase 1 (PLSCR1).	[14]

24 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 Phospholipid scramblase 1 (PLSCR1).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phospholipid scramblase 1 (PLSCR1).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Phospholipid scramblase 1 (PLSCR1).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phospholipid scramblase 1 (PLSCR1).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phospholipid scramblase 1 (PLSCR1).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phospholipid scramblase 1 (PLSCR1).	[20]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Phospholipid scramblase 1 (PLSCR1).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phospholipid scramblase 1 (PLSCR1).	[22]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Phospholipid scramblase 1 (PLSCR1).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phospholipid scramblase 1 (PLSCR1).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Phospholipid scramblase 1 (PLSCR1).	[25]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Phospholipid scramblase 1 (PLSCR1).	[26]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Phospholipid scramblase 1 (PLSCR1).	[27]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Phospholipid scramblase 1 (PLSCR1).	[28]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Phospholipid scramblase 1 (PLSCR1).	[29]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Phospholipid scramblase 1 (PLSCR1).	[30]
Ethanol	DMDRQZU	Approved	Ethanol affects the expression of Phospholipid scramblase 1 (PLSCR1).	[31]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Phospholipid scramblase 1 (PLSCR1).	[32]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Phospholipid scramblase 1 (PLSCR1).	[33]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Phospholipid scramblase 1 (PLSCR1).	[30]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Phospholipid scramblase 1 (PLSCR1).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Phospholipid scramblase 1 (PLSCR1).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Phospholipid scramblase 1 (PLSCR1).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Phospholipid scramblase 1 (PLSCR1).	[36]

References

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