Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1C44F9)

DOT Name ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10)
Synonyms ABC-mitochondrial erythroid protein; ABC-me protein; ATP-binding cassette transporter 10; ABC transporter 10 protein; Mitochondrial ATP-binding cassette 2; M-ABC2
Gene Name ABCB10
Related Disease
Colorectal neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Colorectal carcinoma ( )
Epithelial ovarian cancer ( )
Huntington disease ( )
Non-insulin dependent diabetes ( )
Clear cell renal carcinoma ( )
Bladder cancer ( )
Esophageal squamous cell carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Type-1/2 diabetes ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
UniProt ID
ABCBA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3ZDQ; 4AYT; 4AYW; 4AYX; 7Y48; 7Y49
Pfam ID
PF00664 ; PF00005
Sequence
MRGPPAWPLRLLEPPSPAEPGRLLPVACVWAAASRVPGSLSPFTGLRPARLWGAGPALLW
GVGAARRWRSGCRGGGPGASRGVLGLARLLGLWARGPGSCRCGAFAGPGAPRLPRARFPG
GPAAAAWAGDEAWRRGPAAPPGDKGRLRPAAAGLPEARKLLGLAYPERRRLAAAVGFLTM
SSVISMSAPFFLGKIIDVIYTNPTVDYSDNLTRLCLGLSAVFLCGAAANAIRVYLMQTSG
QRIVNRLRTSLFSSILRQEVAFFDKTRTGELINRLSSDTALLGRSVTENLSDGLRAGAQA
SVGISMMFFVSPNLATFVLSVVPPVSIIAVIYGRYLRKLTKVTQDSLAQATQLAEERIGN
VRTVRAFGKEMTEIEKYASKVDHVMQLARKEAFARAGFFGATGLSGNLIVLSVLYKGGLL
MGSAHMTVGELSSFLMYAFWVGISIGGLSSFYSELMKGLGAGGRLWELLEREPKLPFNEG
VILNEKSFQGALEFKNVHFAYPARPEVPIFQDFSLSIPSGSVTALVGPSGSGKSTVLSLL
LRLYDPASGTISLDGHDIRQLNPVWLRSKIGTVSQEPILFSCSIAENIAYGADDPSSVTA
EEIQRVAEVANAVAFIRNFPQGFNTVVGEKGVLLSGGQKQRIAIARALLKNPKILLLDEA
TSALDAENEYLVQEALDRLMDGRTVLVIAHRLSTIKNANMVAVLDQGKITEYGKHEELLS
KPNGIYRKLMNKQSFISA
Function
Catalyzes the export of an unknown physiological substrate from the mitochondrial matrix to the cytosol in an ATP-dependent manner. May also transport the heme analog Zn (II) mesoporphyrin (ZnMP) in an ATP dependent manner but can't export the heme precursor 5-aminolevulinic acid (ALA) from mitochondria. Plays a role in the early step of the heme biosynthetic process during insertion of iron into protoporphyrin IX (PPIX). In turn participates in hemoglobin synthesis and also protects against oxidative stress. In addition may be involved in mitochondrial unfolded protein response (UPRmt) signaling pathway, although ABCB10 probably does not participate in peptide export from mitochondria.
Tissue Specificity
Ubiquitous. Highly expressed in bone marrow, expressed at intermediate to high levels in skeletal muscle, small intestine, thyroid, heart, brain, placenta, liver, pancreas, prostate, testis, ovary, leukocyte, stomach, spinal cord, lymph node, trachea and adrenal gland, and low levels are found in lung, kidney, spleen, thymus and colon.
KEGG Pathway
ABC transporters (hsa02010 )
Reactome Pathway
Mitochondrial ABC transporters (R-HSA-1369007 )

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colorectal neoplasm DISR1UCN Definitive Biomarker [1]
Breast cancer DIS7DPX1 Strong Biomarker [2]
Breast carcinoma DIS2UE88 Strong Biomarker [2]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [2]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [3]
Huntington disease DISQPLA4 Strong Biomarker [4]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [5]
Clear cell renal carcinoma DISBXRFJ moderate Biomarker [6]
Bladder cancer DISUHNM0 Limited Biomarker [2]
Esophageal squamous cell carcinoma DIS5N2GV Limited Biomarker [2]
Lung cancer DISCM4YA Limited Genetic Variation [2]
Lung carcinoma DISTR26C Limited Genetic Variation [2]
Type-1/2 diabetes DISIUHAP Limited Biomarker [7]
Urinary bladder cancer DISDV4T7 Limited Biomarker [2]
Urinary bladder neoplasm DIS7HACE Limited Biomarker [2]
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⏷ Show the Full List of 15 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10) affects the response to substance of Cisplatin. [18]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [8]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [9]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [10]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [11]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [12]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [13]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [10]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [14]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate increases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [16]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of ATP-binding cassette sub-family B member 10, mitochondrial (ABCB10). [17]
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⏷ Show the Full List of 11 Drug(s)

References

1 The role of ABC transporters in progression and clinical outcome of colorectal cancer.Mutagenesis. 2012 Mar;27(2):187-96. doi: 10.1093/mutage/ger075.
2 The biogenesis and biological functions of circular RNAs and their molecular diagnostic values in cancers.J Clin Lab Anal. 2020 Jan;34(1):e23049. doi: 10.1002/jcla.23049. Epub 2019 Sep 25.
3 Circular RNA ABCB10 correlates with advanced clinicopathological features and unfavorable survival, and promotes cell proliferation while reduces cell apoptosis in epithelial ovarian cancer.Cancer Biomark. 2019;26(2):151-161. doi: 10.3233/CBM-190064.
4 Mutant huntingtin inhibits the mitochondrial unfolded protein response by impairing ABCB10 mRNA stability.Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1428-1435. doi: 10.1016/j.bbadis.2019.02.015. Epub 2019 Feb 23.
5 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
6 Circular RNA ABCB10 promotes tumor progression and correlates with pejorative prognosis in clear cell renal cell carcinoma.Int J Biol Markers. 2019 Jun;34(2):176-183. doi: 10.1177/1724600819842279. Epub 2019 May 20.
7 Blood-brain barrier disruption in diabetic mice is linked to Nrf2 signaling deficits: Role of ABCB10?.Neurosci Lett. 2017 Jul 13;653:152-158. doi: 10.1016/j.neulet.2017.05.059. Epub 2017 May 29.
8 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.
9 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
10 Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis. Life Sci. 2003 Aug 15;73(13):1705-19. doi: 10.1016/s0024-3205(03)00515-0.
11 Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
12 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.
13 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
14 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
15 Impact of epigallocatechin gallate on gene expression profiles of human hepatocellular carcinoma cell lines BEL7404/ADM and BEL7402/5-FU. Ai Zheng. 2008 Oct;27(10):1056-64.
16 Benzo[a]pyrene and glycine N-methyltransferse interactions: gene expression profiles of the liver detoxification pathway. Toxicol Appl Pharmacol. 2006 Jul 15;214(2):126-35.
17 Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
18 Role of transporter genes in cisplatin resistance. In Vivo. 2008 May-Jun;22(3):279-83.