Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF906UR)

• DOT Name: Acyl carrier protein, mitochondrial (NDUFAB1)
• Synonyms: ACP; CI-SDAP; NADH-ubiquinone oxidoreductase 9.6 kDa subunit
• Gene Name: NDUFAB1
• Related Disease:
  Advanced cancer
  Atherosclerosis
  Cardiac failure
  Central retinal vein occlusion
  Congestive heart failure
  Dementia
  Dilated cardiomyopathy
  Endometrial carcinoma
  G6PD deficiency
  Hairy cell leukaemia
  Hereditary nonpolyposis colon cancer
  Neoplasm
  Osteoporosis
  Polyp
  Stroke
  Trichohepatoenteric syndrome
  Tuberculosis
  Wilson disease
  Adult lymphoma
  Benign neoplasm
  Coronary atherosclerosis
  Coronary heart disease
  Gonorrhea
  Lymphoma
  Obesity
  Pediatric lymphoma
  Sexually transmitted infection
  Small lymphocytic lymphoma
• UniProt ID: ACPM_HUMAN
• PDB ID: 2DNW; 5OOL; 5OOM; 5XTB; 5XTC; 5XTD; 5XTH; 5XTI; 6ODD; 7A5H; 7A5J; 7O9K; 7O9M; 7ODR; 7ODS; 7ODT; 7OF0; 7OF2; 7OF3; 7OF5; 7OF7; 7OI6; 7OI7; 7OI8; 7OI9; 7OIC; 7OID; 7OIE; 7PD3; 7PO4; 7QH6; 7QH7
• Pfam ID: PF00550
• Sequence:
  MASRVLSAYVSRLPAAFAPLPRVRMLAVARPLSTALCSAGTQTRLGTLQPALVLAQVPGR
  VTQLCRQYSDMPPLTLEGIQDRVLYVLKLYDKIDPEKLSVNSHFMKDLGLDSLDQVEIIM
  AMEDEFGFEIPDIDAEKLMCPQEIVDYIADKKDVYE
• Function: Carrier of the growing fatty acid chain in fatty acid biosynthesis. Accessory and non-catalytic subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which functions in the transfer of electrons from NADH to the respiratory chain. Accessory protein, of the core iron-sulfur cluster (ISC) assembly complex, that regulates, in association with LYRM4, the stability and the cysteine desulfurase activity of NFS1 and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU. The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Thermogenesis (hsa04714)
  Retrograde endocan.binoid sig.ling (hsa04723)
  Non-alcoholic fatty liver disease (hsa04932)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Respiratory electron transport (R-HSA-611105)
  Complex I biogenesis (R-HSA-6799198)
  Mitochondrial Fatty Acid Beta-Oxidation (R-HSA-77289)
  Glyoxylate metabolism and glycine degradation (R-HSA-389661)
• BioCyc Pathway: MetaCyc:ENSG00000004779-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[3]
Central retinal vein occlusion	DIS5ICKE	Strong	Biomarker	[4]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]
Dementia	DISXL1WY	Strong	Biomarker	[5]
Dilated cardiomyopathy	DISX608J	Strong	Genetic Variation	[3]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[1]
G6PD deficiency	DISYF1GO	Strong	Genetic Variation	[6]
Hairy cell leukaemia	DISTD2E5	Strong	Biomarker	[7]
Hereditary nonpolyposis colon cancer	DISPA49R	Strong	Genetic Variation	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Osteoporosis	DISF2JE0	Strong	Biomarker	[10]
Polyp	DISRSLYF	Strong	Biomarker	[11]
Stroke	DISX6UHX	Strong	Biomarker	[12]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Biomarker	[13]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[14]
Wilson disease	DISVS9H7	Strong	Biomarker	[15]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[16]
Benign neoplasm	DISDUXAD	Limited	Biomarker	[17]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[18]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[18]
Gonorrhea	DISQ5AO6	Limited	Altered Expression	[19]
Lymphoma	DISN6V4S	Limited	Biomarker	[16]
Obesity	DIS47Y1K	Limited	Biomarker	[20]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[16]
Sexually transmitted infection	DISIVIAL	Limited	Altered Expression	[19]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[21]

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 Acyl carrier protein, mitochondrial (NDUFAB1).	[22]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[27]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[28]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[29]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[30]
Fenretinide	DMRD5SP	Phase 3	Fenretinide affects the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[32]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[34]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[35]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Acyl carrier protein, mitochondrial (NDUFAB1).	[36]

References

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• [19] Structure of the Recombinant Neisseria gonorrhoeae Adhesin Complex Protein (rNg-ACP) and Generation of Murine Antibodies with Bactericidal Activity against Gonococci.mSphere. 2018 Oct 10;3(5):e00331-18. doi: 10.1128/mSphere.00331-18.
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