Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSOBOL5)

• DOT Name: ABC-type oligopeptide transporter ABCB9 (ABCB9)
• Synonyms: EC 7.4.2.6; ATP-binding cassette sub-family B member 9; ATP-binding cassette transporter 9; ABC transporter 9 protein; hABCB9; TAP-like protein; TAPL
• Gene Name: ABCB9
• UniProt ID: ABCB9_HUMAN
• EC Number: 7.4.2.6
• Pfam ID: PF00664 ; PF00005
• Sequence:
  MRLWKAVVVTLAFMSVDICVTTAIYVFSHLDRSLLEDIRHFNIFDSVLDLWAACLYRSCL
  LLGATIGVAKNSALGPRRLRASWLVITLVCLFVGIYAMVKLLLFSEVRRPIRDPWFWALF
  VWTYISLGASFLLWWLLSTVRPGTQALEPGAATEAEGFPGSGRPPPEQASGATLQKLLSY
  TKPDVAFLVAASFFLIVAALGETFLPYYTGRAIDGIVIQKSMDQFSTAVVIVCLLAIGSS
  FAAGIRGGIFTLIFARLNIRLRNCLFRSLVSQETSFFDENRTGDLISRLTSDTTMVSDLV
  SQNINVFLRNTVKVTGVVVFMFSLSWQLSLVTFMGFPIIMMVSNIYGKYYKRLSKEVQNA
  LARASNTAEETISAMKTVRSFANEEEEAEVYLRKLQQVYKLNRKEAAAYMYYVWGSGLTL
  LVVQVSILYYGGHLVISGQMTSGNLIAFIIYEFVLGDCMESVGSVYSGLMQGVGAAEKVF
  EFIDRQPTMVHDGSLAPDHLEGRVDFENVTFTYRTRPHTQVLQNVSFSLSPGKVTALVGP
  SGSGKSSCVNILENFYPLEGGRVLLDGKPISAYDHKYLHRVISLVSQEPVLFARSITDNI
  SYGLPTVPFEMVVEAAQKANAHGFIMELQDGYSTETGEKGAQLSGGQKQRVAMARALVRN
  PPVLILDEATSALDAESEYLIQQAIHGNLQKHTVLIIAHRLSTVEHAHLIVVLDKGRVVQ
  QGTHQQLLAQGGLYAKLVQRQMLGLQPAADFTAGHNEPVANGSHKA
• Function: ATP-dependent low-affinity peptide transporter which translocates a broad spectrum of peptides from the cytosol to the lysosomal lumen for degradation. Displays a broad peptide length specificity from 6-mer up to at least 59-mer peptides with an optimum of 23-mers. Binds and transports smaller and larger peptides with the same affinity. Favors positively charged, aromatic or hydrophobic residues in the N- and C-terminal positions whereas negatively charged residues as well as asparagine and methionine are not favored.
• Tissue Specificity: Highly expressed in testis, and at moderate levels in brain, spinal cord, and thyroid. Not expressed in monocytes but strongly expressed during differentiation of monocytes to dendritic cells and macrophages.
• KEGG Pathway:
  ABC transporters (hsa02010)
  Lysosome (hsa04142)
• Reactome Pathway: ABC-family proteins mediated transport (R-HSA-382556)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[3]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[5]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[6]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[7]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[6]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[8]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of ABC-type oligopeptide transporter ABCB9 (ABCB9).	[9]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [6] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [7] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro. Oncotarget. 2014 Dec 30;5(24):12891-907.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.