Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPHD65D)

• DOT Name: Poly(A) polymerase alpha (PAPOLA)
• Synonyms: PAP-alpha; EC 2.7.7.19; Polynucleotide adenylyltransferase alpha
• Gene Name: PAPOLA
• Related Disease:
  Bacteremia
  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
  Neoplasm
  Obesity
  Pancreatic cancer
  Post-traumatic stress disorder
  Precancerous condition
  Pyelonephritis
  Rheumatoid arthritis
  Scleroderma
  Severe combined immunodeficiency
  Sleep apnea syndrome
  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
  Overhydrated hereditary stomatocytosis
  Pancreatitis
  Psychotic disorder
• UniProt ID: PAPOA_HUMAN
• EC Number: 2.7.7.19
• Pfam ID: PF04928 ; PF20750 ; PF04926
• Sequence:
  MPFPVTTQGSQQTQPPQKHYGITSPISLAAPKETDCVLTQKLIETLKPFGVFEEEEELQR
  RILILGKLNNLVKEWIREISESKNLPQSVIENVGGKIFTFGSYRLGVHTKGADIDALCVA
  PRHVDRSDFFTSFYDKLKLQEEVKDLRAVEEAFVPVIKLCFDGIEIDILFARLALQTIPE
  DLDLRDDSLLKNLDIRCIRSLNGCRVTDEILHLVPNIDNFRLTLRAIKLWAKRHNIYSNI
  LGFLGGVSWAMLVARTCQLYPNAIASTLVHKFFLVFSKWEWPNPVLLKQPEECNLNLPVW
  DPRVNPSDRYHLMPIITPAYPQQNSTYNVSVSTRMVMVEEFKQGLAITDEILLSKAEWSK
  LFEAPNFFQKYKHYIVLLASAPTEKQRLEWVGLVESKIRILVGSLEKNEFITLAHVNPQS
  FPAPKENPDKEEFRTMWVIGLVFKKTENSENLSVDLTYDIQSFTDTVYRQAINSKMFEVD
  MKIAAMHVKRKQLHQLLPNHVLQKKKKHSTEGVKLTALNDSSLDLSMDSDNSMSVPSPTS
  ATKTSPLNSSGSSQGRNSPAPAVTAASVTNIQATEVSVPQVNSSESSGGTSSESIPQTAT
  QPAISPPPKPTVSRVVSSTRLVNPPPRSSGNAATSGNAATKIPTPIVGVKRTSSPHKEES
  PKKTKTEEDETSEDANCLALSGHDKTEAKEQLDTETSTTQSETIQTAASLLASQKTSSTD
  LSDIPALPANPIPVIKNSIKLRLNR
• Function: Polymerase that creates the 3'-poly(A) tail of mRNA's. Also required for the endoribonucleolytic cleavage reaction at some polyadenylation sites. May acquire specificity through interaction with a cleavage and polyadenylation specificity factor (CPSF) at its C-terminus.
• KEGG Pathway: mR. surveillance pathway (hsa03015)
• Reactome Pathway:
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  Processing of Intronless Pre-mRNAs (R-HSA-77595)
  mRNA 3'-end processing (R-HSA-72187)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bacteremia	DIS6N9RZ	Definitive	Biomarker	[1]
Obstructive sleep apnea	DIS0SVD1	Definitive	Biomarker	[2]
Parkinson disease	DISQVHKL	Definitive	Biomarker	[3]
Acute pyelonephritis	DISLG5PR	Strong	Genetic Variation	[4]
Adenocarcinoma in situ	DISSTE29	Strong	Biomarker	[5]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[6]
Androgen insensitivity syndrome	DISUZBBO	Strong	Biomarker	[5]
Arrhythmia	DISFF2NI	Strong	Biomarker	[7]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[7]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Biomarker	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[10]
Colitis	DISAF7DD	Strong	Biomarker	[11]
Dysplasia of cervix	DISOAROS	Strong	Genetic Variation	[12]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[6]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[13]
Huntington disease	DISQPLA4	Strong	Biomarker	[10]
leukaemia	DISS7D1V	Strong	Altered Expression	[14]
Leukemia	DISNAKFL	Strong	Genetic Variation	[14]
Male infertility	DISY3YZZ	Strong	Altered Expression	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Obesity	DIS47Y1K	Strong	Biomarker	[17]
Pancreatic cancer	DISJC981	Strong	Biomarker	[18]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[19]
Precancerous condition	DISV06FL	Strong	Biomarker	[20]
Pyelonephritis	DISAOX93	Strong	Biomarker	[21]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[22]
Scleroderma	DISVQ342	Strong	Biomarker	[23]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[14]
Sleep apnea syndrome	DISER6KS	Strong	Biomarker	[24]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[25]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[23]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[17]
Cervical Intraepithelial neoplasia	DISXP757	moderate	Genetic Variation	[12]
Cholangiocarcinoma	DIS71F6X	moderate	Genetic Variation	[26]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[27]
Pulmonary emphysema	DIS5M7HZ	moderate	Biomarker	[26]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[28]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Biomarker	[29]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[30]
Human papillomavirus infection	DISX61LX	Limited	Genetic Variation	[31]
Overhydrated hereditary stomatocytosis	DIS6TF7I	Limited	Biomarker	[32]
Pancreatitis	DIS0IJEF	Limited	Altered Expression	[18]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Poly(A) polymerase alpha (PAPOLA) affects the response to substance of Methotrexate.	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Poly(A) polymerase alpha (PAPOLA).	[34]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Poly(A) polymerase alpha (PAPOLA).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Poly(A) polymerase alpha (PAPOLA).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Poly(A) polymerase alpha (PAPOLA).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Poly(A) polymerase alpha (PAPOLA).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Poly(A) polymerase alpha (PAPOLA).	[39]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Poly(A) polymerase alpha (PAPOLA).	[41]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Poly(A) polymerase alpha (PAPOLA).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Poly(A) polymerase alpha (PAPOLA).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Poly(A) polymerase alpha (PAPOLA).	[45]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Poly(A) polymerase alpha (PAPOLA).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Poly(A) polymerase alpha (PAPOLA).	[47]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Poly(A) polymerase alpha (PAPOLA).	[48]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Poly(A) polymerase alpha (PAPOLA).	[49]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Poly(A) polymerase alpha (PAPOLA).	[50]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Poly(A) polymerase alpha (PAPOLA).	[40]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Poly(A) polymerase alpha (PAPOLA).	[42]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Poly(A) polymerase alpha (PAPOLA).	[44]

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