Details of Drug Off-Target (DOT)

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

• DOT Name: Sterol carrier protein 2 (SCP2)
• Synonyms: SCP-2; Acetyl-CoA C-myristoyltransferase; EC 2.3.1.155; Non-specific lipid-transfer protein; NSL-TP; Propanoyl-CoA C-acyltransferase; EC 2.3.1.176; SCP-2/3-oxoacyl-CoA thiolase; SCP-2/thiolase; EC 2.3.1.16; SCP-chi; SCPX; Sterol carrier protein X; SCP-X
• Gene Name: SCP2
• Related Disease:
  Leukoencephalopathy with vanishing white matter
  Motor peripheral neuropathy
  Paroxysmal dystonia
  Polyneuropathy
  Adrenocortical carcinoma
  Adult Refsum disease
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Congenital contractural arachnodactyly
  Dystonia
  Food allergy
  Hyperglycemia
  Non-alcoholic fatty liver disease
  Pituitary adenoma
  Progressive multifocal leukoencephalopathy
  Sterol carrier protein 2 deficiency
  Vasculitis
  Breast carcinoma
  Connective tissue disorder
• UniProt ID: SCP2_HUMAN
• PDB ID: 1QND; 2C0L
• EC Number: 2.3.1.155; 2.3.1.16; 2.3.1.176
• Pfam ID: PF02036 ; PF02803 ; PF00108
• Sequence:
  MSSSPWEPATLRRVFVVGVGMTKFVKPGAENSRDYPDLAEEAGKKALADAQIPYSAVDQA
  CVGYVFGDSTCGQRAIYHSLGMTGIPIINVNNNCATGSTALFMARQLIQGGVAECVLALG
  FEKMSKGSLGIKFSDRTIPTDKHVDLLINKYGLSAHPVAPQMFGYAGKEHMEKYGTKIEH
  FAKIGWKNHKHSVNNPYSQFQDEYSLDEVMASKEVFDFLTILQCCPTSDGAAAAILASEA
  FVQKYGLQSKAVEILAQEMMTDLPSSFEEKSIIKMVGFDMSKEAARKCYEKSGLTPNDID
  VIELHDCFSTNELLTYEALGLCPEGQGATLVDRGDNTYGGKWVINPSGGLISKGHPLGAT
  GLAQCAELCWQLRGEAGKRQVPGAKVALQHNLGIGGAVVVTLYKMGFPEAASSFRTHQIE
  AVPTSSASDGFKANLVFKEIEKKLEEEGEQFVKKIGGIFAFKVKDGPGGKEATWVVDVKN
  GKGSVLPNSDKKADCTITMADSDFLALMTGKMNPQSAFFQGKLKITGNMGLAMKLQNLQL
  QPGNAKL
• Function: [Isoform SCPx]: Plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids. Catalyzes the last step of the peroxisomal beta-oxidation of branched chain fatty acids and the side chain of the bile acid intermediates di- and trihydroxycoprostanic acids (DHCA and THCA). Also active with medium and long straight chain 3-oxoacyl-CoAs. Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol and transfers phosphatidylcholine and 7-dehydrocholesterol between membrances, in vitro. Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs; [Isoform SCP2]: Mediates the transfer of all common phospholipids, cholesterol and gangliosides from the endoplasmic reticulum to the plasma membrane. May play a role in regulating steroidogenesis. Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol. Also binds fatty acids and fatty acyl Coenzyme A (CoA) such as phytanoyl-CoA. Involved in the regulation phospholipid synthesis in endoplasmic reticulum enhancing the incorporation of exogenous fatty acid into glycerides. Seems to stimulate the rate-limiting step in phosphatidic acid formation mediated by GPAT3. Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs.
• Tissue Specificity: Liver, fibroblasts, and placenta.
• KEGG Pathway:
  Primary bile acid biosynthesis (hsa00120)
  Biosynthesis of unsaturated fatty acids (hsa01040)
  Metabolic pathways (hsa01100)
  Fatty acid metabolism (hsa01212)
  PPAR sig.ling pathway (hsa03320)
  Peroxisome (hsa04146)
• Reactome Pathway:
  Peroxisomal protein import (R-HSA-9033241)
  TYSND1 cleaves peroxisomal proteins (R-HSA-9033500)
  alpha-linolenic acid (ALA) metabolism (R-HSA-2046106)
• BioCyc Pathway: MetaCyc:HS03991-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leukoencephalopathy with vanishing white matter	DIS3J8NN	Definitive	Biomarker	[1]
Motor peripheral neuropathy	DISVNBSJ	Definitive	Biomarker	[1]
Paroxysmal dystonia	DISV0MSQ	Definitive	Biomarker	[1]
Polyneuropathy	DISB9G3W	Definitive	Biomarker	[1]
Adrenocortical carcinoma	DISZF4HX	Strong	Biomarker	[2]
Adult Refsum disease	DISU2BLL	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[7]
Dystonia	DISJLFGW	Strong	Biomarker	[1]
Food allergy	DISMQ1BP	Strong	Biomarker	[8]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[9]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[10]
Pituitary adenoma	DISJ5R1X	Strong	Altered Expression	[11]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[12]
Sterol carrier protein 2 deficiency	DIS3O072	Strong	Autosomal recessive	[1]
Vasculitis	DISQRKDX	Strong	Biomarker	[13]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[6]
Connective tissue disorder	DISKXBS3	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Sterol carrier protein 2 (SCP2).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sterol carrier protein 2 (SCP2).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sterol carrier protein 2 (SCP2).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sterol carrier protein 2 (SCP2).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sterol carrier protein 2 (SCP2).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sterol carrier protein 2 (SCP2).	[20]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Sterol carrier protein 2 (SCP2).	[21]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Sterol carrier protein 2 (SCP2).	[22]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of Sterol carrier protein 2 (SCP2).	[23]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of Sterol carrier protein 2 (SCP2).	[24]
Nevirapine	DM6HX9B	Approved	Nevirapine increases the expression of Sterol carrier protein 2 (SCP2).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sterol carrier protein 2 (SCP2).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sterol carrier protein 2 (SCP2).	[27]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Sterol carrier protein 2 (SCP2).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sterol carrier protein 2 (SCP2).	[30]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sterol carrier protein 2 (SCP2).	[31]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Sterol carrier protein 2 (SCP2).	[32]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Sterol carrier protein 2 (SCP2).	[34]

2 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 decreases the methylation of Sterol carrier protein 2 (SCP2).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Sterol carrier protein 2 (SCP2).	[28]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone affects the localization of Sterol carrier protein 2 (SCP2).	[33]

References

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