Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXSK5LP)

• DOT Name: Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC)
• Synonyms: 130 kDa leucine-rich protein; LRP 130; GP130
• Gene Name: LRPPRC
• Related Disease:
  Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type
  Cytochrome-c oxidase deficiency disease
  Leigh syndrome
  Alzheimer disease
  Asthma
  Autoimmune disease
  Bladder cancer
  Cardiac failure
  Colorectal carcinoma
  Congestive heart failure
  Endometrial carcinoma
  Hepatocellular carcinoma
  Kaposi sarcoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Medulloblastoma
  Mitochondrial disease
  Myocardial infarction
  Neoplasm
  Non-insulin dependent diabetes
  Osteoarthritis
  Parkinson disease
  Plasma cell myeloma
  Prostate carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Head-neck squamous cell carcinoma
  Multiple sclerosis
  Pancreatic cancer
  Triple negative breast cancer
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Epithelial ovarian cancer
  Melanoma
  Non-small-cell lung cancer
  Obesity
  Ovarian cancer
  Ovarian neoplasm
  Systemic sclerosis
  Type-1/2 diabetes
• UniProt ID: LPPRC_HUMAN
• PDB ID: 8ANY
• Pfam ID: PF01535 ; PF13812 ; PF17177
• Sequence:
  MAALLRSARWLLRAGAAPRLPLSLRLLPGGPGRLHAASYLPAARAGPVAGGLLSPARLYA
  IAAKEKDIQEESTFSSRKISNQFDWALMRLDLSVRRTGRIPKKLLQKVFNDTCRSGGLGG
  SHALLLLRSCGSLLPELKLEERTEFAHRIWDTLQKLGAVYDVSHYNALLKVYLQNEYKFS
  PTDFLAKMEEANIQPNRVTYQRLIASYCNVGDIEGASKILGFMKTKDLPVTEAVFSALVT
  GHARAGDMENAENILTVMRDAGIEPGPDTYLALLNAYAEKGDIDHVKQTLEKVEKSELHL
  MDRDLLQIIFSFSKAGYPQYVSEILEKVTCERRYIPDAMNLILLLVTEKLEDVALQILLA
  CPVSKEDGPSVFGSFFLQHCVTMNTPVEKLTDYCKKLKEVQMHSFPLQFTLHCALLANKT
  DLAKALMKAVKEEGFPIRPHYFWPLLVGRRKEKNVQGIIEILKGMQELGVHPDQETYTDY
  VIPCFDSVNSARAILQENGCLSDSDMFSQAGLRSEAANGNLDFVLSFLKSNTLPISLQSI
  RSSLLLGFRRSMNINLWSEITELLYKDGRYCQEPRGPTEAVGYFLYNLIDSMSDSEVQAK
  EEHLRQYFHQLEKMNVKIPENIYRGIRNLLESYHVPELIKDAHLLVESKNLDFQKTVQLT
  SSELESTLETLKAENQPIRDVLKQLILVLCSEENMQKALELKAKYESDMVTGGYAALINL
  CCRHDKVEDALNLKEEFDRLDSSAVLDTGKYVGLVRVLAKHGKLQDAINILKEMKEKDVL
  IKDTTALSFFHMLNGAALRGEIETVKQLHEAIVTLGLAEPSTNISFPLVTVHLEKGDLST
  ALEVAIDCYEKYKVLPRIHDVLCKLVEKGETDLIQKAMDFVSQEQGEMVMLYDLFFAFLQ
  TGNYKEAKKIIETPGIRARSARLQWFCDRCVANNQVETLEKLVELTQKLFECDRDQMYYN
  LLKLYKINGDWQRADAVWNKIQEENVIPREKTLRLLAEILREGNQEVPFDVPELWYEDEK
  HSLNSSSASTTEPDFQKDILIACRLNQKKGAYDIFLNAKEQNIVFNAETYSNLIKLLMSE
  DYFTQAMEVKAFAETHIKGFTLNDAANSRLIITQVRRDYLKEAVTTLKTVLDQQQTPSRL
  AVTRVIQALAMKGDVENIEVVQKMLNGLEDSIGLSKMVFINNIALAQIKNNNIDAAIENI
  ENMLTSENKVIEPQYFGLAYLFRKVIEEQLEPAVEKISIMAERLANQFAIYKPVTDFFLQ
  LVDAGKVDDARALLQRCGAIAEQTPILLLFLLRNSRKQGKASTVKSVLELIPELNEKEEA
  YNSLMKSYVSEKDVTSAKALYEHLTAKNTKLDDLFLKRYASLLKYAGEPVPFIEPPESFE
  FYAQQLRKLRENSS
• Function: May play a role in RNA metabolism in both nuclei and mitochondria. In the nucleus binds to HNRPA1-associated poly(A) mRNAs and is part of nmRNP complexes at late stages of mRNA maturation which are possibly associated with nuclear mRNA export. Positively modulates nuclear export of mRNAs containing the EIF4E sensitivity element (4ESE) by binding simultaneously to both EIF4E and the 4ESE and acting as a platform for assembly for the RNA export complex. Also binds to exportin XPO1/CRM1 to engage the nuclear pore and traffic the bound mRNAs to the cytoplasm. May bind mature mRNA in the nucleus outer membrane. In mitochondria binds to poly(A) mRNA. Plays a role in translation or stability of mitochondrially encoded cytochrome c oxidase (COX) subunits. May be involved in transcription regulation. Cooperates with PPARGC1A to regulate certain mitochondrially encoded genes and gluconeogenic genes and may regulate docking of PPARGC1A to transcription factors. Seems to be involved in the transcription regulation of the multidrug-related genes MDR1 and MVP. Part of a nuclear factor that binds to the invMED1 element of MDR1 and MVP gene promoters. Binds single-stranded DNA.
• Tissue Specificity: Expressed ubiquitously. Expression is highest in heart, skeletal muscle, kidney and liver, intermediate in brain, non-mucosal colon, spleen and placenta, and lowest in small intestine, thymus, lung and peripheral blood leukocytes.
• Reactome Pathway:
  Respiratory electron transport (R-HSA-611105)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Mitochondrial RNA degradation (R-HSA-9836573)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	DISVZ0PJ	Definitive	Autosomal recessive	[1]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Definitive	Autosomal recessive	[2]
Leigh syndrome	DISWQU45	Definitive	Autosomal recessive	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Asthma	DISW9QNS	Strong	Biomarker	[4]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[6]
Cardiac failure	DISDC067	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[7]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[10]
Kaposi sarcoma	DISC1H1Z	Strong	Biomarker	[11]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[13]
Lung carcinoma	DISTR26C	Strong	Biomarker	[13]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[14]
Mitochondrial disease	DISKAHA3	Strong	Biomarker	[15]
Myocardial infarction	DIS655KI	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[17]
Osteoarthritis	DIS05URM	Strong	Biomarker	[18]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[19]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[20]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[21]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[6]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[6]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[22]
Multiple sclerosis	DISB2WZI	moderate	Biomarker	[23]
Pancreatic cancer	DISJC981	moderate	Biomarker	[24]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[25]
Acute lymphocytic leukaemia	DISPX75S	Limited	Altered Expression	[26]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[26]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[27]
Breast cancer	DIS7DPX1	Limited	Biomarker	[28]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[28]
Colon cancer	DISVC52G	Limited	Biomarker	[29]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[29]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[30]
Melanoma	DIS1RRCY	Limited	Biomarker	[31]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[32]
Obesity	DIS47Y1K	Limited	Biomarker	[33]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[30]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[30]
Systemic sclerosis	DISF44L6	Limited	Altered Expression	[34]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[35]

2 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 Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC).	[36]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC).	[39]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Leucine-rich PPR motif-containing protein, mitochondrial (LRPPRC).	[45]

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