Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT34G4US)

• DOT Name: ATP-binding cassette sub-family C member 5 (ABCC5)
• Synonyms: EC 7.6.2.-; EC 7.6.2.2; Multi-specific organic anion transporter C; MOAT-C; Multidrug resistance-associated protein 5; SMRP; pABC11
• Gene Name: ABCC5
• UniProt ID: MRP5_HUMAN
• EC Number: 7.6.2.-; 7.6.2.2
• Pfam ID: PF00664 ; PF00005
• Sequence:
  MKDIDIGKEYIIPSPGYRSVRERTSTSGTHRDREDSKFRRTRPLECQDALETAARAEGLS
  LDASMHSQLRILDEEHPKGKYHHGLSALKPIRTTSKHQHPVDNAGLFSCMTFSWLSSLAR
  VAHKKGELSMEDVWSLSKHESSDVNCRRLERLWQEELNEVGPDAASLRRVVWIFCRTRLI
  LSIVCLMITQLAGFSGPAFMVKHLLEYTQATESNLQYSLLLVLGLLLTEIVRSWSLALTW
  ALNYRTGVRLRGAILTMAFKKILKLKNIKEKSLGELINICSNDGQRMFEAAAVGSLLAGG
  PVVAILGMIYNVIILGPTGFLGSAVFILFYPAMMFASRLTAYFRRKCVAATDERVQKMNE
  VLTYIKFIKMYAWVKAFSQSVQKIREEERRILEKAGYFQSITVGVAPIVVVIASVVTFSV
  HMTLGFDLTAAQAFTVVTVFNSMTFALKVTPFSVKSLSEASVAVDRFKSLFLMEEVHMIK
  NKPASPHIKIEMKNATLAWDSSHSSIQNSPKLTPKMKKDKRASRGKKEKVRQLQRTEHQA
  VLAEQKGHLLLDSDERPSPEEEEGKHIHLGHLRLQRTLHSIDLEIQEGKLVGICGSVGSG
  KTSLISAILGQMTLLEGSIAISGTFAYVAQQAWILNATLRDNILFGKEYDEERYNSVLNS
  CCLRPDLAILPSSDLTEIGERGANLSGGQRQRISLARALYSDRSIYILDDPLSALDAHVG
  NHIFNSAIRKHLKSKTVLFVTHQLQYLVDCDEVIFMKEGCITERGTHEELMNLNGDYATI
  FNNLLLGETPPVEINSKKETSGSQKKSQDKGPKTGSVKKEKAVKPEEGQLVQLEEKGQGS
  VPWSVYGVYIQAAGGPLAFLVIMALFMLNVGSTAFSTWWLSYWIKQGSGNTTVTRGNETS
  VSDSMKDNPHMQYYASIYALSMAVMLILKAIRGVVFVKGTLRASSRLHDELFRRILRSPM
  KFFDTTPTGRILNRFSKDMDEVDVRLPFQAEMFIQNVILVFFCVGMIAGVFPWFLVAVGP
  LVILFSVLHIVSRVLIRELKRLDNITQSPFLSHITSSIQGLATIHAYNKGQEFLHRYQEL
  LDDNQAPFFLFTCAMRWLAVRLDLISIALITTTGLMIVLMHGQIPPAYAGLAISYAVQLT
  GLFQFTVRLASETEARFTSVERINHYIKTLSLEAPARIKNKAPSPDWPQEGEVTFENAEM
  RYRENLPLVLKKVSFTIKPKEKIGIVGRTGSGKSSLGMALFRLVELSGGCIKIDGVRISD
  IGLADLRSKLSIIPQEPVLFSGTVRSNLDPFNQYTEDQIWDALERTHMKECIAQLPLKLE
  SEVMENGDNFSVGERQLLCIARALLRHCKILILDEATAAMDTETDLLIQETIREAFADCT
  MLTIAHRLHTVLGSDRIMVLAQGQVVEFDTPSVLLSNDSSRFYAMFAAAENKVAVKG
• Function: ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro). Acts also as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins. Confers resistance to the antiviral agent PMEA. Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated. Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway. May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells.
• Tissue Specificity: .Predominant isoform in retinal pigment epithelium, bladder, and stomach.; Ubiquitously expressed, but levels in brain and muscle are especially high . All isoforms are equally expressed in retina .
• KEGG Pathway:
  Antifolate resistance (hsa01523)
  ABC transporters (hsa02010)
• Reactome Pathway:
  ABC-family proteins mediated transport (R-HSA-382556)
  Azathioprine ADME (R-HSA-9748787)
  Paracetamol ADME (R-HSA-9753281)
  Hyaluronan biosynthesis and export (R-HSA-2142850)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 7 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	ATP-binding cassette sub-family C member 5 (ABCC5) decreases the response to substance of Doxorubicin.	[27]
Cisplatin	DMRHGI9	Approved	ATP-binding cassette sub-family C member 5 (ABCC5) decreases the response to substance of Cisplatin.	[28]
Quercetin	DM3NC4M	Approved	ATP-binding cassette sub-family C member 5 (ABCC5) decreases the response to substance of Quercetin.	[29]
Fluorouracil	DMUM7HZ	Approved	ATP-binding cassette sub-family C member 5 (ABCC5) decreases the response to substance of Fluorouracil.	[30]
Pemetrexed	DMMX2E6	Approved	ATP-binding cassette sub-family C member 5 (ABCC5) decreases the response to substance of Pemetrexed.	[27]
Thioguanine	DM7NKEV	Approved	ATP-binding cassette sub-family C member 5 (ABCC5) decreases the response to substance of Thioguanine.	[27]
Resveratrol	DM3RWXL	Phase 3	ATP-binding cassette sub-family C member 5 (ABCC5) decreases the response to substance of Resveratrol.	[29]

This DOT Affected the Regulation of Drug Effects of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Glutathione	DMAHMT9	Approved	ATP-binding cassette sub-family C member 5 (ABCC5) affects the transport of Glutathione.	[31]
5-Fluoro-2'-Deoxyuridine-5'-Monophosphate	DME1AGO	Investigative	ATP-binding cassette sub-family C member 5 (ABCC5) increases the export of 5-Fluoro-2'-Deoxyuridine-5'-Monophosphate.	[27]
2'-deoxyuridylic acid	DMPV1LU	Investigative	ATP-binding cassette sub-family C member 5 (ABCC5) increases the export of 2'-deoxyuridylic acid.	[27]

28 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 ATP-binding cassette sub-family C member 5 (ABCC5).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[3]
Aspirin	DM672AH	Approved	Aspirin increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[9]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[10]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[11]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[13]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone affects the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[14]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[15]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[3]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[17]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[19]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[22]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[24]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[26]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[3]
U0126	DM31OGF	Investigative	U0126 decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[18]
Chrysin	DM7V2LG	Investigative	Chrysin decreases the expression of ATP-binding cassette sub-family C member 5 (ABCC5).	[18]

3 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 ATP-binding cassette sub-family C member 5 (ABCC5).	[16]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of ATP-binding cassette sub-family C member 5 (ABCC5).	[23]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of ATP-binding cassette sub-family C member 5 (ABCC5).	[25]

References

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