Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPDUX30)

• DOT Name: Biotin--protein ligase (HLCS)
• Synonyms: EC 6.3.4.-; Biotin apo-protein ligase) ligase (EC 6.3.4.9); Biotin--] ligase (EC 6.3.4.10; Holocarboxylase synthetase; HCS); Biotin-- ligase (EC 6.3.4.11); Biotin-- ligase (EC 6.3.4.15)]
• Gene Name: HLCS
• Related Disease:
  Choriocarcinoma
  Holocarboxylase synthetase deficiency
  Breast cancer
  Breast carcinoma
  Chediak-Higashi syndrome
  Chondrosarcoma
  Head and neck neoplasm
  Hereditary hyperferritinemia with congenital cataracts
  Macular corneal dystrophy
  Multiple carboxylase deficiency
  Specific language impairment
  Tuberculosis
  Biotinidase deficiency
  Biotin metabolic disease
  Cystinuria
  Hypotonia-cystinuria syndrome
• UniProt ID: BPL1_HUMAN
• EC Number: 6.3.4.-; 6.3.4.10; 6.3.4.11; 6.3.4.15; 6.3.4.9
• Pfam ID: PF02237 ; PF03099
• Sequence:
  MEDRLHMDNGLVPQKIVSVHLQDSTLKEVKDQVSNKQAQILEPKPEPSLEIKPEQDGMEH
  VGRDDPKALGEEPKQRRGSASGSEPAGDSDRGGGPVEHYHLHLSSCHECLELENSTIESV
  KFASAENIPDLPYDYSSSLESVADETSPEREGRRVNLTGKAPNILLYVGSDSQEALGRFH
  EVRSVLADCVDIDSYILYHLLEDSALRDPWTDNCLLLVIATRESIPEDLYQKFMAYLSQG
  GKVLGLSSSFTFGGFQVTSKGALHKTVQNLVFSKADQSEVKLSVLSSGCRYQEGPVRLSP
  GRLQGHLENEDKDRMIVHVPFGTRGGEAVLCQVHLELPPSSNIVQTPEDFNLLKSSNFRR
  YEVLREILTTLGLSCDMKQVPALTPLYLLSAAEEIRDPLMQWLGKHVDSEGEIKSGQLSL
  RFVSSYVSEVEITPSCIPVVTNMEAFSSEHFNLEIYRQNLQTKQLGKVILFAEVTPTTMR
  LLDGLMFQTPQEMGLIVIAARQTEGKGRGGNVWLSPVGCALSTLLISIPLRSQLGQRIPF
  VQHLMSVAVVEAVRSIPEYQDINLRVKWPNDIYYSDLMKIGGVLVNSTLMGETFYILIGC
  GFNVTNSNPTICINDLITEYNKQHKAELKPLRADYLIARVVTVLEKLIKEFQDKGPNSVL
  PLYYRYWVHSGQQVHLGSAEGPKVSIVGLDDSGFLQVHQEGGEVVTVHPDGNSFDMLRNL
  ILPKRR
• Function: Biotin--protein ligase catalyzing the biotinylation of the 4 biotin-dependent carboxylases acetyl-CoA-carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase.
• Tissue Specificity: Widely expressed . Mostly expressed in muscle, placenta and to a lower extent in the brain, kidney, pancreas, liver and lung .
• KEGG Pathway:
  Biotin metabolism (hsa00780)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Defective HLCS causes multiple carboxylase deficiency (R-HSA-3371599)
  Biotin transport and metabolism (R-HSA-196780)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Choriocarcinoma	DISDBVNL	Definitive	Altered Expression	[1]
Holocarboxylase synthetase deficiency	DISY6SW9	Definitive	Autosomal recessive	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Chediak-Higashi syndrome	DISPJLLO	Strong	Biomarker	[4]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[5]
Head and neck neoplasm	DIS1OB2G	Strong	Biomarker	[6]
Hereditary hyperferritinemia with congenital cataracts	DISGL689	Strong	Altered Expression	[7]
Macular corneal dystrophy	DISOLD0H	Strong	Genetic Variation	[8]
Multiple carboxylase deficiency	DISV3SZX	Strong	Altered Expression	[8]
Specific language impairment	DISEKRML	Strong	Genetic Variation	[9]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[10]
Biotinidase deficiency	DISFHBBV	moderate	Altered Expression	[11]
Biotin metabolic disease	DISX6152	Limited	Altered Expression	[12]
Cystinuria	DISCU7CO	Limited	Biomarker	[13]
Hypotonia-cystinuria syndrome	DISUPMRI	Limited	Genetic Variation	[13]

29 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 Biotin--protein ligase (HLCS).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Biotin--protein ligase (HLCS).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Biotin--protein ligase (HLCS).	[16]
Quercetin	DM3NC4M	Approved	Quercetin decreases the activity of Biotin--protein ligase (HLCS).	[18]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Biotin--protein ligase (HLCS).	[19]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Biotin--protein ligase (HLCS).	[20]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Biotin--protein ligase (HLCS).	[21]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Biotin--protein ligase (HLCS).	[19]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Biotin--protein ligase (HLCS).	[22]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Biotin--protein ligase (HLCS).	[23]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Biotin--protein ligase (HLCS).	[23]
Vitamin C	DMXJ7O8	Approved	Vitamin C decreases the activity of Biotin--protein ligase (HLCS).	[18]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Biotin--protein ligase (HLCS).	[24]
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	3,4-Dihydroxycinnamic Acid decreases the activity of Biotin--protein ligase (HLCS).	[18]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the activity of Biotin--protein ligase (HLCS).	[18]
Fumaric acid	DMP83UZ	Phase 3	Fumaric acid decreases the activity of Biotin--protein ligase (HLCS).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Biotin--protein ligase (HLCS).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Biotin--protein ligase (HLCS).	[26]
Ferulic Acid	DMJC7NF	Patented	Ferulic Acid decreases the activity of Biotin--protein ligase (HLCS).	[18]
4-Hydroxybenzoicacid	DM3WQNY	Patented	4-Hydroxybenzoicacid decreases the activity of Biotin--protein ligase (HLCS).	[18]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Biotin--protein ligase (HLCS).	[28]
Citrate	DM37NYK	Preclinical	Citrate decreases the activity of Biotin--protein ligase (HLCS).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Biotin--protein ligase (HLCS).	[29]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the activity of Biotin--protein ligase (HLCS).	[18]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID decreases the activity of Biotin--protein ligase (HLCS).	[18]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid decreases the activity of Biotin--protein ligase (HLCS).	[18]
Piceatannol	DMYOP45	Investigative	Piceatannol decreases the activity of Biotin--protein ligase (HLCS).	[18]
P-Coumaric Acid	DMGJSVD	Investigative	P-Coumaric Acid decreases the activity of Biotin--protein ligase (HLCS).	[18]
CYANIDIN	DMZBDO1	Investigative	CYANIDIN decreases the activity of Biotin--protein ligase (HLCS).	[18]

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 Biotin--protein ligase (HLCS).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Biotin--protein ligase (HLCS).	[27]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Biotin--protein ligase (HLCS).	[27]

References

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