Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHLZY8D)

• DOT Name: Membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3)
• Synonyms: Phosphatidylinositol transfer protein, membrane-associated 3; PITPnm 3; Pyk2 N-terminal domain-interacting receptor 1; NIR-1
• Gene Name: PITPNM3
• Related Disease:
  Hepatocellular carcinoma
  Advanced cancer
  Age-related macular degeneration
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Cone-rod dystrophy 5
  Hereditary macular dystrophy
  Neoplasm
  Retinitis pigmentosa
  Retinitis pigmentosa 12
  Vascular purpura
  Vitelliform macular dystrophy
  Cone-rod dystrophy
  Matthew-Wood syndrome
• UniProt ID: PITM3_HUMAN
• Pfam ID: PF02862
• Sequence:
  MAKAGRAGGPPPGGGAPWHLRNVLSDSVESSDDEFFDAREEMAEGKNAILIGMSQWNSND
  LVEQIETMGKLDEHQGEGTAPCTSSILQEKQRELYRVSLRRQRFPAQGSIEIHEDSEEGC
  PQRSCKTHVLLLVLHGGNILDTGAGDPSCKAADIHTFSSVLEKVTRAHFPAALGHILIKF
  VPCPAICSEAFSLVSHLNPYSHDEGCLSSSQDHVPLAALPLLAISSPQYQDAVATVIERA
  NQVYREFLKSSDGIGFSGQVCLIGDCVGGLLAFDAICYSAGPSGDSPASSSRKGSISSTQ
  DTPVAVEEDCSLASSKRLSKSNIDISSGLEDEEPKRPLPRKQSDSSTYDCEAITQHHAFL
  SSIHSSVLKDESETPAAGGPQLPEVSLGRFDFDVSDFFLFGSPLGLVLAMRRTVLPGLDG
  FQVRPACSQVYSFFHCADPSASRLEPLLEPKFHLVPPVSVPRYQRFPLGDGQSLLLADAL
  HTHSPLFLEGSSRDSPPLLDAPASPPQASRFQRPGRRMSEGSSHSESSESSDSMAPVGAS
  RITAKWWGSKRIDYALYCPDVLTAFPTVALPHLFHASYWESTDVVAFILRQVMRYESVNI
  KESARLDPAALSPANPREKWLRKRTQVKLRNVTANHRANDVIAAEDGPQVLVGRFMYGPL
  DMVALTGEKVDILVMAEPSSGRWVHLDTEITNSSGRITYNVPRPRRLGVGVYPVKMVVRG
  DQTCAMSYLTVLPRGMECVVFSIDGSFAASVSIMGSDPKVRPGAVDVVRHWQDLGYMILY
  ITGRPDMQKQRVVSWLSQHNFPQGMIFFSDGLVHDPLRQKAIFLRNLMQECFIKISAAYG
  STKDISVYSVLGLPASQIFIVGRPTKKYQTQCQFLSEGYAAHLAALEASHRSRPKKNNSR
  MILRKGSFGLHAQPEFLRKRNHLRRTMSVQQPDPPAANPKPERAQSQPESDKDHERPLPA
  LSWARGPPKFESVP
• Function: Catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes (in vitro). Binds calcium ions.
• Tissue Specificity: Detected in brain and spleen, and at low levels in ovary.
• Reactome Pathway: Synthesis of PI (R-HSA-1483226)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cone-rod dystrophy 5	DISZTDDR	Strong	Autosomal dominant	[6]
Hereditary macular dystrophy	DISEYSYY	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[3]
Retinitis pigmentosa 12	DIS90SAO	Strong	Genetic Variation	[3]
Vascular purpura	DIS6ZZMF	Strong	Genetic Variation	[8]
Vitelliform macular dystrophy	DISEFYYN	Strong	Biomarker	[3]
Cone-rod dystrophy	DISY9RWN	Supportive	Autosomal dominant	[6]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[9]

3 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 Membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3).	[13]

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 decreases the methylation of Membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3).	[12]

References

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• [2] A molecular design strategy toward enzyme-activated probes with near-infrared I and II fluorescence for targeted cancer imaging.Chem Sci. 2019 Jun 14;10(30):7222-7227. doi: 10.1039/c9sc02093d. eCollection 2019 Aug 14.
• [3] Analysis of peripherin/RDS gene for Japanese retinal dystrophies.Jpn J Ophthalmol. 1998 May-Jun;42(3):186-92. doi: 10.1016/s0021-5155(97)00133-0.
• [4] Bright Aggregation-Induced-Emission Dots for Targeted Synergetic NIR-II Fluorescence and NIR-I Photoacoustic Imaging of Orthotopic Brain Tumors.Adv Mater. 2018 May 28:e1800766. doi: 10.1002/adma.201800766. Online ahead of print.
• [5] Discovery of CCL18 antagonist blocking breast cancer metastasis.Clin Exp Metastasis. 2019 Jun;36(3):243-255. doi: 10.1007/s10585-019-09965-2. Epub 2019 May 6.
• [6] Mutation in the PYK2-binding domain of PITPNM3 causes autosomal dominant cone dystrophy (CORD5) in two Swedish families. Eur J Hum Genet. 2007 Jun;15(6):664-71. doi: 10.1038/sj.ejhg.5201817. Epub 2007 Mar 21.
• [7] Nanocatalysts-Augmented and Photothermal-Enhanced Tumor-Specific Sequential Nanocatalytic Therapy in Both NIR-I and NIR-II Biowindows.Adv Mater. 2019 Feb;31(5):e1805919. doi: 10.1002/adma.201805919. Epub 2018 Dec 9.
• [8] Engineered Exosome-Mediated Near-Infrared-II Region V(2)C Quantum Dot Delivery for Nucleus-Target Low-Temperature Photothermal Therapy.ACS Nano. 2019 Feb 26;13(2):1499-1510. doi: 10.1021/acsnano.8b07224. Epub 2019 Jan 29.
• [9] Tumor-associated macrophages promote progression and the Warburg effect via CCL18/NF-kB/VCAM-1 pathway in pancreatic ductal adenocarcinoma.Cell Death Dis. 2018 May 1;9(5):453. doi: 10.1038/s41419-018-0486-0.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.