Details of Drug Off-Target (DOT)

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

DOT Name Matrix-remodeling-associated protein 5 (MXRA5)
Synonyms Adhesion protein with leucine-rich repeats and immunoglobulin domains related to perlecan; Adlican
Gene Name MXRA5
Related Disease
Advanced cancer ( )
Chronic kidney disease ( )
Lung cancer ( )
Lung carcinoma ( )
Non-small-cell lung cancer ( )
Renal cell carcinoma ( )
Intellectual disability ( )
Schizophrenia ( )
UniProt ID
MXRA5_HUMAN
Pfam ID
PF07679 ; PF13927 ; PF13855
Sequence
MPKRAHWGALSVVLILLWGHPRVALACPHPCACYVPSEVHCTFRSLASVPAGIAKHVERI
NLGFNSIQALSETSFAGLTKLELLMIHGNEIPSIPDGALRDLSSLQVFKFSYNKLRVITG
QTLQGLSNLMRLHIDHNKIEFIHPQAFNGLTSLRLLHLEGNLLHQLHPSTFSTFTFLDYF
RLSTIRHLYLAENMVRTLPASMLRNMPLLENLYLQGNPWTCDCEMRWFLEWDAKSRGILK
CKKDKAYEGGQLCAMCFSPKKLYKHEIHKLKDMTCLKPSIESPLRQNRSRSIEEEQEQEE
DGGSQLILEKFQLPQWSISLNMTDEHGNMVNLVCDIKKPMDVYKIHLNQTDPPDIDINAT
VALDFECPMTRENYEKLWKLIAYYSEVPVKLHRELMLSKDPRVSYQYRQDADEEALYYTG
VRAQILAEPEWVMQPSIDIQLNRRQSTAKKVLLSYYTQYSQTISTKDTRQARGRSWVMIE
PSGAVQRDQTVLEGGPCQLSCNVKASESPSIFWVLPDGSILKAPMDDPDSKFSILSSGWL
RIKSMEPSDSGLYQCIAQVRDEMDRMVYRVLVQSPSTQPAEKDTVTIGKNPGESVTLPCN
ALAIPEAHLSWILPNRRIINDLANTSHVYMLPNGTLSIPKVQVSDSGYYRCVAVNQQGAD
HFTVGITVTKKGSGLPSKRGRRPGAKALSRVREDIVEDEGGSGMGDEENTSRRLLHPKDQ
EVFLKTKDDAINGDKKAKKGRRKLKLWKHSEKEPETNVAEGRRVFESRRRINMANKQINP
ERWADILAKVRGKNLPKGTEVPPLIKTTSPPSLSLEVTPPFPAISPPSASPVQTVTSAEE
SSADVPLLGEEEHVLGTISSASMGLEHNHNGVILVEPEVTSTPLEEVVDDLSEKTEEITS
TEGDLKGTAAPTLISEPYEPSPTLHTLDTVYEKPTHEETATEGWSAADVGSSPEPTSSEY
EPPLDAVSLAESEPMQYFDPDLETKSQPDEDKMKEDTFAHLTPTPTIWVNDSSTSQLFED
STIGEPGVPGQSHLQGLTDNIHLVKSSLSTQDTLLIKKGMKEMSQTLQGGNMLEGDPTHS
RSSESEGQESKSITLPDSTLGIMSSMSPVKKPAETTVGTLLDKDTTTATTTPRQKVAPSS
TMSTHPSRRRPNGRRRLRPNKFRHRHKQTPPTTFAPSETFSTQPTQAPDIKISSQVESSL
VPTAWVDNTVNTPKQLEMEKNAEPTSKGTPRRKHGKRPNKHRYTPSTVSSRASGSKPSPS
PENKHRNIVTPSSETILLPRTVSLKTEGPYDSLDYMTTTRKIYSSYPKVQETLPVTYKPT
SDGKEIKDDVATNVDKHKSDILVTGESITNAIPTSRSLVSTMGEFKEESSPVGFPGTPTW
NPSRTAQPGRLQTGIPVTTSGENLTDPPLLKELEDVDFTSEFLSSLTVSTPFHQEEAGSS
TTLSSIKVEVASSQAETTTLDQDHLETTVAILLSETRPQNHTPTAARMKEPASSSPSTIL
MSLGQTTTTKPALPSPRISQASRDSKENVFLNYVGNPETEATPVNNEGTQHMSGPNELST
PSSDQDAFNLSTKLELEKQVFGSRSLPRGPDSQRQDGRVHASHQLTRVPAKPILPTATVR
LPEMSTQSASRYFVTSQSPRHWTNKPEITTYPSGALPENKQFTTPRLSSTTIPLPLHMSK
PSIPSKFTDRRTDQFNGYSKVFGNNNIPEARNPVGKPPSPRIPHYSNGRLPFFTNKTLSF
PQLGVTRRPQIPTSPAPVMRERKVIPGSYNRIHSHSTFHLDFGPPAPPLLHTPQTTGSPS
TNLQNIPMVSSTQSSISFITSSVQSSGSFHQSSSKFFAGGPPASKFWSLGEKPQILTKSP
QTVSVTAETDTVFPCEATGKPKPFVTWTKVSTGALMTPNTRIQRFEVLKNGTLVIRKVQV
QDRGQYMCTASNLHGLDRMVVLLSVTVQQPQILASHYQDVTVYLGDTIAMECLAKGTPAP
QISWIFPDRRVWQTVSPVEGRITLHENRTLSIKEASFSDRGVYKCVASNAAGADSLAIRL
HVAALPPVIHQEKLENISLPPGLSIHIHCTAKAAPLPSVRWVLGDGTQIRPSQFLHGNLF
VFPNGTLYIRNLAPKDSGRYECVAANLVGSARRTVQLNVQRAAANARITGTSPRRTDVRY
GGTLKLDCSASGDPWPRILWRLPSKRMIDALFSFDSRIKVFANGTLVVKSVTDKDAGDYL
CVARNKVGDDYVVLKVDVVMKPAKIEHKEENDHKVFYGGDLKVDCVATGLPNPEISWSLP
DGSLVNSFMQSDDSGGRTKRYVVFNNGTLYFNEVGMREEGDYTCFAENQVGKDEMRVRVK
VVTAPATIRNKTYLAVQVPYGDVVTVACEAKGEPMPKVTWLSPTNKVIPTSSEKYQIYQD
GTLLIQKAQRSDSGNYTCLVRNSAGEDRKTVWIHVNVQPPKINGNPNPITTVREIAAGGS
RKLIDCKAEGIPTPRVLWAFPEGVVLPAPYYGNRITVHGNGSLDIRSLRKSDSVQLVCMA
RNEGGEARLILQLTVLEPMEKPIFHDPISEKITAMAGHTISLNCSAAGTPTPSLVWVLPN
GTDLQSGQQLQRFYHKADGMLHISGLSSVDAGAYRCVARNAAGHTERLVSLKVGLKPEAN
KQYHNLVSIINGETLKLPCTPPGAGQGRFSWTLPNGMHLEGPQTLGRVSLLDNGTLTVRE
ASVFDRGTYVCRMETEYGPSVTSIPVIVIAYPPRITSEPTPVIYTRPGNTVKLNCMAMGI
PKADITWELPDKSHLKAGVQARLYGNRFLHPQGSLTIQHATQRDAGFYKCMAKNILGSDS
KTTYIHVF
Function In kidney, has anti-inflammatory and anti-fibrotic properties by limiting the induction of chemokines, fibronectin and collagen expression in response to TGB1 and pro-inflammatory stimuli.
Tissue Specificity
Detected in placenta (at protein level) . Detected in cerebrospinal fluid and fibroblasts (at protein level) . Highly expressed in kidney, also detected on liver and spleen . Expressed by proximal tubular cells of the kidney (at protein level) . Expression highly increases during chronic kidney disease and autosomal dominant polycystic kidney disease, where is detected in cysts .

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Chronic kidney disease DISW82R7 Strong Biomarker [2]
Lung cancer DISCM4YA Strong Biomarker [3]
Lung carcinoma DISTR26C Strong Genetic Variation [4]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [3]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [2]
Intellectual disability DISMBNXP Disputed Genetic Variation [5]
Schizophrenia DISSRV2N Disputed Biomarker [5]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
19 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 Matrix-remodeling-associated protein 5 (MXRA5). [6]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [7]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [10]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Matrix-remodeling-associated protein 5 (MXRA5). [11]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [12]
Progesterone DMUY35B Approved Progesterone decreases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [13]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [15]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [16]
Azathioprine DMMZSXQ Approved Azathioprine increases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [12]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Matrix-remodeling-associated protein 5 (MXRA5). [17]
Piroxicam DMTK234 Approved Piroxicam increases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [12]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [18]
Permethrin DMZ0Q1G Approved Permethrin decreases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [19]
Ethinyl estradiol DMODJ40 Approved Ethinyl estradiol affects the expression of Matrix-remodeling-associated protein 5 (MXRA5). [20]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [21]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Matrix-remodeling-associated protein 5 (MXRA5). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Matrix-remodeling-associated protein 5 (MXRA5). [23]
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⏷ Show the Full List of 19 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the methylation of Matrix-remodeling-associated protein 5 (MXRA5). [14]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Matrix-remodeling-associated protein 5 (MXRA5). [22]
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References

1 Matrix remodeling associated 5 expression in trunk and limb during avian development.Int J Dev Biol. 2018;62(4-5):335-340. doi: 10.1387/ijdb.170225ac.
2 MXRA5 is a TGF-1-regulated human protein with anti-inflammatory and anti-fibrotic properties.J Cell Mol Med. 2017 Jan;21(1):154-164. doi: 10.1111/jcmm.12953. Epub 2016 Sep 6.
3 Matrix-remodeling associated 5 as a novel tissue biomarker predicts poor prognosis in non-small cell lung cancers.Cancer Biomark. 2015;15(5):645-51. doi: 10.3233/CBM-150504.
4 Exome sequencing identifies MXRA5 as a novel cancer gene frequently mutated in non-small cell lung carcinoma from Chinese patients.Carcinogenesis. 2012 Sep;33(9):1797-805. doi: 10.1093/carcin/bgs210. Epub 2012 Jun 13.
5 Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families.Sci Rep. 2017 Jul 18;7(1):5679. doi: 10.1038/s41598-017-06033-1.
6 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
7 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
8 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
9 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.
10 Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
11 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
12 Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
13 Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
14 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.
15 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.
16 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
17 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
18 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
19 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
20 The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
21 Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
22 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.
23 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.