Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6HQ02S)

• DOT Name: Poly(A) RNA polymerase, mitochondrial (MTPAP)
• Synonyms: PAP; EC 2.7.7.19; PAP-associated domain-containing protein 1; Polynucleotide adenylyltransferase; Terminal uridylyltransferase 1; TUTase 1; mtPAP
• Gene Name: MTPAP
• Related Disease:
  Bacteremia
  Mitochondrial disease
  Obstructive sleep apnea
  Parkinson disease
  Acute pyelonephritis
  Adenocarcinoma in situ
  Adult glioblastoma
  Androgen insensitivity syndrome
  Arrhythmia
  Atrial fibrillation
  Autosomal dominant optic atrophy, classic form
  Cervical cancer
  Cervical carcinoma
  Classic Hodgkin lymphoma
  Colitis
  Dysplasia of cervix
  Glioblastoma multiforme
  Hepatitis B virus infection
  Huntington disease
  leukaemia
  Leukemia
  Male infertility
  Melanoma
  Neoplasm
  Obesity
  Pancreatic cancer
  Post-traumatic stress disorder
  Precancerous condition
  Pyelonephritis
  Scleroderma
  Severe combined immunodeficiency
  Sleep apnea syndrome
  Spastic ataxia 4
  Systemic lupus erythematosus
  Systemic sclerosis
  Type-1/2 diabetes
  Cervical Intraepithelial neoplasia
  Cholangiocarcinoma
  Methicillin-resistant staphylococci infection
  Pulmonary emphysema
  Amyotrophic lateral sclerosis
  Chronic obstructive pulmonary disease
  Colorectal carcinoma
  Human papillomavirus infection
  Pancreatitis
  Psychotic disorder
• UniProt ID: PAPD1_HUMAN
• PDB ID: 3PQ1
• EC Number: 2.7.7.19
• Pfam ID: PF03828 ; PF17797
• Sequence:
  MAVPGVGLLTRLNLCARRRTRVQRPIVRLLSCPGTVAKDLRRDEQPSGSVETGFEDKIPK
  RRFSEMQNERREQAQRTVLIHCPEKISENKFLKYLSQFGPINNHFFYESFGLYAVVEFCQ
  KESIGSLQNGTHTPSTAMETAIPFRSRFFNLKLKNQTSERSRVRSSNQLPRSNKQLFELL
  CYAESIDDQLNTLLKEFQLTEENTKLRYLTCSLIEDMAAAYFPDCIVRPFGSSVNTFGKL
  GCDLDMFLDLDETRNLSAHKISGNFLMEFQVKNVPSERIATQKILSVLGECLDHFGPGCV
  GVQKILNARCPLVRFSHQASGFQCDLTTNNRIALTSSELLYIYGALDSRVRALVFSVRCW
  ARAHSLTSSIPGAWITNFSLTMMVIFFLQRRSPPILPTLDSLKTLADAEDKCVIEGNNCT
  FVRDLSRIKPSQNTETLELLLKEFFEYFGNFAFDKNSINIRQGREQNKPDSSPLYIQNPF
  ETSLNISKNVSQSQLQKFVDLARESAWILQQEDTDRPSISSNRPWGLVSLLLPSAPNRKS
  FTKKKSNKFAIETVKNLLESLKGNRTENFTKTSGKRTISTQT
• Function: Polymerase that creates the 3' poly(A) tail of mitochondrial transcripts. Can use all four nucleotides, but has higher activity with ATP and UTP (in vitro). Plays a role in replication-dependent histone mRNA degradation. May be involved in the terminal uridylation of mature histone mRNAs before their degradation is initiated. Might be responsible for the creation of some UAA stop codons which are not encoded in mtDNA.
• Tissue Specificity: Ubiquitous, with stronger expression in tissues with high energy requirements: heart, brain, and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bacteremia	DIS6N9RZ	Definitive	Biomarker	[1]
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[2]
Obstructive sleep apnea	DIS0SVD1	Definitive	Biomarker	[3]
Parkinson disease	DISQVHKL	Definitive	Biomarker	[4]
Acute pyelonephritis	DISLG5PR	Strong	Genetic Variation	[5]
Adenocarcinoma in situ	DISSTE29	Strong	Biomarker	[6]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[7]
Androgen insensitivity syndrome	DISUZBBO	Strong	Biomarker	[6]
Arrhythmia	DISFF2NI	Strong	Biomarker	[8]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[8]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Biomarker	[9]
Cervical cancer	DISFSHPF	Strong	Biomarker	[10]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[10]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[11]
Colitis	DISAF7DD	Strong	Biomarker	[12]
Dysplasia of cervix	DISOAROS	Strong	Genetic Variation	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[7]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[14]
Huntington disease	DISQPLA4	Strong	Biomarker	[11]
leukaemia	DISS7D1V	Strong	Altered Expression	[15]
Leukemia	DISNAKFL	Strong	Genetic Variation	[15]
Male infertility	DISY3YZZ	Strong	Altered Expression	[16]
Melanoma	DIS1RRCY	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Obesity	DIS47Y1K	Strong	Biomarker	[19]
Pancreatic cancer	DISJC981	Strong	Biomarker	[20]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[21]
Precancerous condition	DISV06FL	Strong	Biomarker	[22]
Pyelonephritis	DISAOX93	Strong	Biomarker	[23]
Scleroderma	DISVQ342	Strong	Biomarker	[24]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[15]
Sleep apnea syndrome	DISER6KS	Strong	Biomarker	[25]
Spastic ataxia 4	DIS5JMQC	Strong	Autosomal recessive	[26]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[27]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[24]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[19]
Cervical Intraepithelial neoplasia	DISXP757	moderate	Genetic Variation	[13]
Cholangiocarcinoma	DIS71F6X	moderate	Genetic Variation	[28]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[29]
Pulmonary emphysema	DIS5M7HZ	moderate	Biomarker	[28]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[30]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[31]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[32]
Human papillomavirus infection	DISX61LX	Limited	Genetic Variation	[33]
Pancreatitis	DIS0IJEF	Limited	Altered Expression	[20]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[34]

12 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 Poly(A) RNA polymerase, mitochondrial (MTPAP).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[39]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[40]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[41]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[46]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[47]

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 affects the methylation of Poly(A) RNA polymerase, mitochondrial (MTPAP).	[43]

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