Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8AKP1J)

• DOT Name: ATP-binding cassette sub-family B member 5 (ABCB5)
• Synonyms: ABCB5 P-gp; P-glycoprotein ABCB5; EC 7.6.2.2
• Gene Name: ABCB5
• UniProt ID: ABCB5_HUMAN
• EC Number: 7.6.2.2
• Pfam ID: PF00664 ; PF00005
• Sequence:
  MENSERAEEMQENYQRNGTAEEQPKLRKEAVGSIEIFRFADGLDITLMILGILASLVNGA
  CLPLMPLVLGEMSDNLISGCLVQTNTTNYQNCTQSQEKLNEDMTLLTLYYVGIGVAALIF
  GYIQISLWIITAARQTKRIRKQFFHSVLAQDIGWFDSCDIGELNTRMTDDIDKISDGIGD
  KIALLFQNMSTFSIGLAVGLVKGWKLTLVTLSTSPLIMASAAACSRMVISLTSKELSAYS
  KAGAVAEEVLSSIRTVIAFRAQEKELQRYTQNLKDAKDFGIKRTIASKVSLGAVYFFMNG
  TYGLAFWYGTSLILNGEPGYTIGTVLAVFFSVIHSSYCIGAAVPHFETFAIARGAAFHIF
  QVIDKKPSIDNFSTAGYKPESIEGTVEFKNVSFNYPSRPSIKILKGLNLRIKSGETVALV
  GLNGSGKSTVVQLLQRLYDPDDGFIMVDENDIRALNVRHYRDHIGVVSQEPVLFGTTISN
  NIKYGRDDVTDEEMERAAREANAYDFIMEFPNKFNTLVGEKGAQMSGGQKQRIAIARALV
  RNPKILILDEATSALDSESKSAVQAALEKASKGRTTIVVAHRLSTIRSADLIVTLKDGML
  AEKGAHAELMAKRGLYYSLVMSQDIKKADEQMESMTYSTERKTNSLPLHSVKSIKSDFID
  KAEESTQSKEISLPEVSLLKILKLNKPEWPFVVLGTLASVLNGTVHPVFSIIFAKIITMF
  GNNDKTTLKHDAEIYSMIFVILGVICFVSYFMQGLFYGRAGEILTMRLRHLAFKAMLYQD
  IAWFDEKENSTGGLTTILAIDIAQIQGATGSRIGVLTQNATNMGLSVIISFIYGWEMTFL
  ILSIAPVLAVTGMIETAAMTGFANKDKQELKHAGKIATEALENIRTIVSLTREKAFEQMY
  EEMLQTQHRNTSKKAQIIGSCYAFSHAFIYFAYAAGFRFGAYLIQAGRMTPEGMFIVFTA
  IAYGAMAIGETLVLAPEYSKAKSGAAHLFALLEKKPNIDSRSQEGKKPDTCEGNLEFREV
  SFFYPCRPDVFILRGLSLSIERGKTVAFVGSSGCGKSTSVQLLQRLYDPVQGQVLFDGVD
  AKELNVQWLRSQIAIVPQEPVLFNCSIAENIAYGDNSRVVPLDEIKEAANAANIHSFIEG
  LPEKYNTQVGLKGAQLSGGQKQRLAIARALLQKPKILLLDEATSALDNDSEKVVQHALDK
  ARTGRTCLVVTHRLSAIQNADLIVVLHNGKIKEQGTHQELLRNRDIYFKLVNAQSVQ
• Function: Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells. Specifically present in limbal stem cells, where it plays a key role in corneal development and repair.
• Tissue Specificity: Expressed by CD133-expressing progenitor cells among epidermal melanocytes (at protein level). Widely expressed with specific expression in pigment cells. Highly expressed in several malignant tissues: highly expressed in clinical melanomas, with low expression in normal skin. In melanoma, marks malignant melanoma-initiating cells (MMIC), in which clinical virulence resides as a consequence of unlimited self-renewal capacity, resulting in inexorable tumor progression and metastasis. Also highly expressed in a number of leukemia cells. Expressed in basal limbal epithelium.
• KEGG Pathway: ABC transporters (hsa02010)
• Reactome Pathway: ABC-family proteins mediated transport (R-HSA-382556)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	ATP-binding cassette sub-family B member 5 (ABCB5) decreases the response to substance of Doxorubicin.	[6]
OXYQUINOLINE	DMZVS9Y	Investigative	ATP-binding cassette sub-family B member 5 (ABCB5) affects the response to substance of OXYQUINOLINE.	[7]

4 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 B member 5 (ABCB5).	[1]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of ATP-binding cassette sub-family B member 5 (ABCB5).	[2]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of ATP-binding cassette sub-family B member 5 (ABCB5).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of ATP-binding cassette sub-family B member 5 (ABCB5).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of ATP-binding cassette sub-family B member 5 (ABCB5).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of ATP-binding cassette sub-family B member 5 (ABCB5).	[4]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [3] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [4] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [5] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [6] ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Res. 2005 May 15;65(10):4320-33.
• [7] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.