Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFBW889)

• DOT Name: Pantothenate kinase 2, mitochondrial (PANK2)
• Synonyms: hPanK2; EC 2.7.1.33; Pantothenic acid kinase 2
• Gene Name: PANK2
• Related Disease:
  Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration
  Schimke immuno-osseous dysplasia
  Aceruloplasminemia
  Adult glioblastoma
  Adult respiratory distress syndrome
  Advanced cancer
  Alzheimer disease
  Anorexia nervosa cachexia
  Azoospermia
  Benign prostatic hyperplasia
  Cervical Intraepithelial neoplasia
  Chorea-acanthocytosis
  Choreatic disease
  Dystonia
  Glioblastoma multiforme
  Hallermann-Streiff syndrome
  Huntington disease
  Hypobetalipoproteinemia
  Inborn error of metabolism
  Leigh syndrome
  Lesch-Nyhan syndrome
  Major depressive disorder
  Malabsorption syndrome
  Movement disorder
  Myelodysplastic syndrome
  Neoplasm
  Neurodegeneration with brain iron accumulation 2A
  Neurodegeneration with brain iron accumulation 5
  Pantothenate kinase-associated neurodegeneration
  Parkinsonian disorder
  Prostate cancer
  Prostate carcinoma
  Retinitis pigmentosa
  Schizophrenia
  Schwartz-Jampel syndrome
  Toxic epidermal necrolysis
  Wilson disease
  Neurodegenerative disease
  Essential tremor
  Hereditary hemochromatosis
  Huntington disease-like 2
  Ankylosing spondylitis
  Cardiomyopathy
  Eosinophilic esophagitis
  Kearns-Sayre syndrome
  Neuroblastoma
  Parkinson disease
• UniProt ID: PANK2_HUMAN
• PDB ID: 5.00E+26
• EC Number: 2.7.1.33
• Pfam ID: PF03630
• Sequence:
  MRRLGPFHPRVHWAAPPSLSSGLHRLLFLRGTRIPSSTTLSPPRHDSLSLDGGTVNPPRV
  REPTGREAFGPSPASSDWLPARWRNGRGGRPRARLCSGWTAAEEARRNPTLGGLLGRQRL
  LLRMGGGRLGAPMERHGRASATSVSSAGEQAAGDPEGRRQEPLRRRASSASVPAVGASAE
  GTRRDRLGSYSGPTSVSRQRVESLRKKRPLFPWFGLDIGGTLVKLVYFEPKDITAEEEEE
  EVESLKSIRKYLTSNVAYGSTGIRDVHLELKDLTLCGRKGNLHFIRFPTHDMPAFIQMGR
  DKNFSSLHTVFCATGGGAYKFEQDFLTIGDLQLCKLDELDCLIKGILYIDSVGFNGRSQC
  YYFENPADSEKCQKLPFDLKNPYPLLLVNIGSGVSILAVYSKDNYKRVTGTSLGGGTFFG
  LCCLLTGCTTFEEALEMASRGDSTKVDKLVRDIYGGDYERFGLPGWAVASSFGNMMSKEK
  REAVSKEDLARATLITITNNIGSIARMCALNENINQVVFVGNFLRINTIAMRLLAYALDY
  WSKGQLKALFSEHEGYFGAVGALLELLKIP
• Function: [Isoform 1]: Mitochondrial isoform that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis. Required for angiogenic activity of umbilical vein of endothelial cells (HUVEC) ; [Isoform 4]: Cytoplasmic isoform that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.
• Tissue Specificity: Expressed in the brain (at protein level) . Ubiquitous . Highly expressed in the testis . Expressed in the umbilical vein endothelial cells (HUVEC) .
• KEGG Pathway:
  Pantothe.te and CoA biosynthesis (hsa00770)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Coenzyme A biosynthesis (R-HSA-196783)
• BioCyc Pathway: MetaCyc:HS13177-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration	DISBN8XM	Definitive	Autosomal recessive	[1]
Schimke immuno-osseous dysplasia	DISGEL3Z	Definitive	Genetic Variation	[2]
Aceruloplasminemia	DISDVY3R	Strong	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Adult respiratory distress syndrome	DISIJV47	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Altered Expression	[8]
Azoospermia	DIS94181	Strong	Biomarker	[9]
Benign prostatic hyperplasia	DISI3CW2	Strong	Biomarker	[10]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Genetic Variation	[11]
Chorea-acanthocytosis	DISW1V6N	Strong	Biomarker	[3]
Choreatic disease	DISH8K3M	Strong	Genetic Variation	[12]
Dystonia	DISJLFGW	Strong	Biomarker	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Hallermann-Streiff syndrome	DISNT5DL	Strong	Biomarker	[14]
Huntington disease	DISQPLA4	Strong	Biomarker	[15]
Hypobetalipoproteinemia	DIS0TPI3	Strong	Biomarker	[3]
Inborn error of metabolism	DISO5FAY	Strong	Genetic Variation	[16]
Leigh syndrome	DISWQU45	Strong	Genetic Variation	[17]
Lesch-Nyhan syndrome	DISGXKU7	Strong	Biomarker	[18]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[19]
Malabsorption syndrome	DISGMUVS	Strong	Genetic Variation	[20]
Movement disorder	DISOJJ2D	Strong	Biomarker	[21]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[22]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Neurodegeneration with brain iron accumulation 2A	DIS9XEBF	Strong	Biomarker	[23]
Neurodegeneration with brain iron accumulation 5	DISW9SFJ	Strong	Genetic Variation	[24]
Pantothenate kinase-associated neurodegeneration	DIS50V55	Strong	Autosomal recessive	[25]
Parkinsonian disorder	DISHGY45	Strong	Genetic Variation	[26]
Prostate cancer	DISF190Y	Strong	Biomarker	[10]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[10]
Retinitis pigmentosa	DISCGPY8	Strong	CausalMutation	[27]
Schizophrenia	DISSRV2N	Strong	Biomarker	[28]
Schwartz-Jampel syndrome	DIS3HCR8	Strong	Biomarker	[29]
Toxic epidermal necrolysis	DISIWPFR	Strong	Biomarker	[29]
Wilson disease	DISVS9H7	Strong	Biomarker	[15]
Neurodegenerative disease	DISM20FF	moderate	Biomarker	[30]
Essential tremor	DIS7GBKQ	Disputed	Genetic Variation	[31]
Hereditary hemochromatosis	DISVG5MT	Disputed	Genetic Variation	[26]
Huntington disease-like 2	DISM3G09	Disputed	Genetic Variation	[3]
Ankylosing spondylitis	DISRC6IR	Limited	Biomarker	[32]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[33]
Eosinophilic esophagitis	DISR8WSB	Limited	Biomarker	[34]
Kearns-Sayre syndrome	DIS9UK5R	Limited	Biomarker	[35]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[36]
Parkinson disease	DISQVHKL	Limited	Biomarker	[22]

3 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 Pantothenate kinase 2, mitochondrial (PANK2).	[37]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Pantothenate kinase 2, mitochondrial (PANK2).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Pantothenate kinase 2, mitochondrial (PANK2).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pantothenate kinase 2, mitochondrial (PANK2).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Pantothenate kinase 2, mitochondrial (PANK2).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Pantothenate kinase 2, mitochondrial (PANK2).	[40]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Pantothenate kinase 2, mitochondrial (PANK2).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Pantothenate kinase 2, mitochondrial (PANK2).	[43]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Pantothenate kinase 2, mitochondrial (PANK2).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Pantothenate kinase 2, mitochondrial (PANK2).	[45]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Pantothenate kinase 2, mitochondrial (PANK2).	[46]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Pantothenate kinase 2, mitochondrial (PANK2).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pantothenate kinase 2, mitochondrial (PANK2).	[48]

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