Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYB58S2)

• DOT Name: ATP-binding cassette sub-family C member 12 (ABCC12)
• Synonyms: Multidrug resistance-associated protein 9
• Gene Name: ABCC12
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
• UniProt ID: MRP9_HUMAN
• Pfam ID: PF00664 ; PF00005
• Sequence:
  MVGEGPYLISDLDQRGRRRSFAERYDPSLKTMIPVRPCARLAPNPVDDAGLLSFATFSWL
  TPVMVKGYRQRLTVDTLPPLSTYDSSDTNAKRFRVLWDEEVARVGPEKASLSHVVWKFQR
  TRVLMDIVANILCIIMAAIGPVILIHQILQQTERTSGKVWVGIGLCIALFATEFTKVFFW
  ALAWAINYRTAIRLKVALSTLVFENLVSFKTLTHISVGEVLNILSSDSYSLFEAALFCPL
  PATIPILMVFCAAYAFFILGPTALIGISVYVIFIPVQMFMAKLNSAFRRSAILVTDKRVQ
  TMNEFLTCIRLIKMYAWEKSFTNTIQDIRRRERKLLEKAGFVQSGNSALAPIVSTIAIVL
  TLSCHILLRRKLTAPVAFSVIAMFNVMKFSIAILPFSIKAMAEANVSLRRMKKILIDKSP
  PSYITQPEDPDTVLLLANATLTWEHEASRKSTPKKLQNQKRHLCKKQRSEAYSERSPPAK
  GATGPEEQSDSLKSVLHSISFVVRKGKILGICGNVGSGKSSLLAALLGQMQLQKGVVAVN
  GTLAYVSQQAWIFHGNVRENILFGEKYDHQRYQHTVRVCGLQKDLSNLPYGDLTEIGERG
  LNLSGGQRQRISLARAVYSDRQLYLLDDPLSAVDAHVGKHVFEECIKKTLRGKTVVLVTH
  QLQFLESCDEVILLEDGEICEKGTHKELMEERGRYAKLIHNLRGLQFKDPEHLYNAAMVE
  AFKESPAEREEDAGIIVLAPGNEKDEGKESETGSEFVDTKVPEHQLIQTESPQEGTVTWK
  TYHTYIKASGGYLLSLFTVFLFLLMIGSAAFSNWWLGLWLDKGSRMTCGPQGNRTMCEVG
  AVLADIGQHVYQWVYTASMVFMLVFGVTKGFVFTKTTLMASSSLHDTVFDKILKSPMSFF
  DTTPTGRLMNRFSKDMDELDVRLPFHAENFLQQFFMVVFILVILAAVFPAVLLVVASLAV
  GFFILLRIFHRGVQELKKVENVSRSPWFTHITSSMQGLGIIHAYGKKESCITYHLLYFNC
  ALRWFALRMDVLMNILTFTVALLVTLSFSSISTSSKGLSLSYIIQLSGLLQVCVRTGTET
  QAKFTSVELLREYISTCVPECTHPLKVGTCPKDWPSRGEITFRDYQMRYRDNTPLVLDSL
  NLNIQSGQTVGIVGRTGSGKSSLGMALFRLVEPASGTIFIDEVDICILSLEDLRTKLTVI
  PQDPVLFVGTVRYNLDPFESHTDEMLWQVLERTFMRDTIMKLPEKLQAEVTENGENFSVG
  ERQLLCVARALLRNSKIILLDEATASMDSKTDTLVQNTIKDAFKGCTVLTIAHRLNTVLN
  CDHVLVMENGKVIEFDKPEVLAEKPDSAFAMLLAAEVRL
• Function: Probable transporter, its substrate specificity is unknown.
• Tissue Specificity: Expressed in testis (at protein level). Widely expressed at low level . Isoform 5 is specifically expressed in brain, testis and breast cancer cells .
• KEGG Pathway: ABC transporters (hsa02010)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of ATP-binding cassette sub-family C member 12 (ABCC12).	[3]
Marinol	DM70IK5	Approved	Marinol increases the expression of ATP-binding cassette sub-family C member 12 (ABCC12).	[4]

References

• [1] Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases.FEBS J. 2011 Sep;278(18):3226-45. doi: 10.1111/j.1742-4658.2011.08235.x. Epub 2011 Aug 1.
• [2] MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer.Proc Natl Acad Sci U S A. 2002 May 14;99(10):6997-7002. doi: 10.1073/pnas.102187299.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.