Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBM30SW)

DOT Name	Myelin and lymphocyte protein (MAL)
Synonyms	T-lymphocyte maturation-associated protein
Gene Name	MAL
Related Disease	Acute megakaryoblastic leukemia ( ) Prostate cancer ( ) Prostate carcinoma ( ) Actinic keratosis ( ) Adenocarcinoma ( ) Adenoma ( ) B-cell lymphoma ( ) Barrett esophagus ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Carcinoma ( ) Carcinoma of esophagus ( ) Cervical Intraepithelial neoplasia ( ) Childhood acute megakaryoblastic leukemia ( ) Classic Hodgkin lymphoma ( ) Colorectal adenoma ( ) Colorectal neoplasm ( ) Endometrial cancer ( ) Endometrial carcinoma ( ) Esophageal cancer ( ) Gastric cancer ( ) Head and neck cancer ( ) Head and neck carcinoma ( ) Head-neck squamous cell carcinoma ( ) Hepatocellular carcinoma ( ) Herpes simplex infection ( ) Leukemia ( ) Lung neoplasm ( ) Neoplasm of esophagus ( ) Prostate neoplasm ( ) Stomach cancer ( ) Head and neck neoplasm ( ) Squamous cell carcinoma ( ) Advanced cancer ( ) Cutaneous squamous cell carcinoma ( ) Epithelial ovarian cancer ( ) Gastric neoplasm ( ) Glioblastoma multiforme ( ) Ovarian cancer ( ) Rheumatoid arthritis ( ) Skin cancer ( ) Stroke ( )
UniProt ID	MAL_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF01284
Sequence	MAPAAATGGSTLPSGFSVFTTLPDLLFIFEFIFGGLVWILVASSLVPWPLVQGWVMFVSV FCFVATTTLIILYIIGAHGGETSWVTLDAAYHCTAALFYLSASVLEALATITMQDGFTYR HYHENIAAVVFSYIATLLYVVHAVFSLIRWKSS
Function	Could be an important component in vesicular trafficking cycling between the Golgi complex and the apical plasma membrane. Could be involved in myelin biogenesis and/or myelin function.

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute megakaryoblastic leukemia	DIS0JX3M	Definitive	Genetic Variation	[1]
Prostate cancer	DISF190Y	Definitive	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[2]
Actinic keratosis	DISR1RC5	Strong	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[5]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[6]
Barrett esophagus	DIS416Y7	Strong	Posttranslational Modification	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[9]
Carcinoma	DISH9F1N	Strong	Posttranslational Modification	[10]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[7]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Biomarker	[11]
Childhood acute megakaryoblastic leukemia	DIS5VZDR	Strong	Altered Expression	[12]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[13]
Colorectal adenoma	DISTSVHM	Strong	Posttranslational Modification	[5]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[5]
Endometrial cancer	DISW0LMR	Strong	Posttranslational Modification	[14]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[14]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[15]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[16]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[17]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[17]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[19]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[20]
Leukemia	DISNAKFL	Strong	Biomarker	[21]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[22]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[15]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[23]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[16]
Head and neck neoplasm	DIS1OB2G	moderate	Biomarker	[17]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[24]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[25]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[26]
Gastric neoplasm	DISOKN4Y	Limited	Posttranslational Modification	[27]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[28]
Ovarian cancer	DISZJHAP	Limited	Altered Expression	[26]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[29]
Skin cancer	DISTM18U	Limited	Biomarker	[24]
Stroke	DISX6UHX	Limited	Biomarker	[30]
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⏷ Show the Full List of 43 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

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	Myelin and lymphocyte protein (MAL) affects the response to substance of Cisplatin.	[43]
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13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Myelin and lymphocyte protein (MAL).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Myelin and lymphocyte protein (MAL).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Myelin and lymphocyte protein (MAL).	[33]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Myelin and lymphocyte protein (MAL).	[34]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Myelin and lymphocyte protein (MAL).	[9]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Myelin and lymphocyte protein (MAL).	[36]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Myelin and lymphocyte protein (MAL).	[37]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Myelin and lymphocyte protein (MAL).	[38]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Myelin and lymphocyte protein (MAL).	[38]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Myelin and lymphocyte protein (MAL).	[39]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myelin and lymphocyte protein (MAL).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Myelin and lymphocyte protein (MAL).	[37]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Myelin and lymphocyte protein (MAL).	[42]
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⏷ Show the Full List of 13 Drug(s)

1 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 increases the methylation of Myelin and lymphocyte protein (MAL).	[40]
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References

1	Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study.Blood. 2015 Sep 24;126(13):1575-84. doi: 10.1182/blood-2015-02-629204. Epub 2015 Jul 27.
2	A novel DNA methylation score accurately predicts death from prostate cancer in men with low to intermediate clinical risk factors.Oncotarget. 2016 Nov 1;7(44):71833-71840. doi: 10.18632/oncotarget.12377.
3	Methyl aminolevulinate daylight photodynamic therapy applied at home for non-hyperkeratotic actinic keratosis of the face or scalp: an open, interventional study conducted in Germany.J Eur Acad Dermatol Venereol. 2019 Apr;33(4):661-666. doi: 10.1111/jdv.15422. Epub 2019 Feb 22.
4	On The Role of Myelin and Lymphocyte Protein (MAL) In Cancer: A Puzzle With Two Faces.J Cancer. 2019 May 21;10(10):2312-2318. doi: 10.7150/jca.30376. eCollection 2019.
5	Hypermethylated MAL gene - a silent marker of early colon tumorigenesis.J Transl Med. 2008 Mar 17;6:13. doi: 10.1186/1479-5876-6-13.
6	Performance of a Commercially Available MAL Antibody in the Diagnosis of Primary Mediastinal Large B-Cell Lymphoma.Am J Surg Pathol. 2017 Feb;41(2):189-194. doi: 10.1097/PAS.0000000000000771.
7	MAL hypermethylation is a tissue-specific event that correlates with MAL mRNA expression in esophageal carcinoma.Sci Rep. 2013 Oct 3;3:2838. doi: 10.1038/srep02838.
8	Differential promoter methylation of kinesin family member 1a in plasma is associated with breast cancer and DNA repair capacity.Oncol Rep. 2014 Aug;32(2):505-12. doi: 10.3892/or.2014.3262. Epub 2014 Jun 13.
9	Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy. Mol Cancer Res. 2009 Feb;7(2):199-209. doi: 10.1158/1541-7786.MCR-08-0314. Epub 2009 Feb 10.
10	CADM1 and MAL promoter methylation levels in hrHPV-positive cervical scrapes increase proportional to degree and duration of underlying cervical disease.Int J Cancer. 2013 Sep 15;133(6):1293-9. doi: 10.1002/ijc.28138. Epub 2013 Apr 4.
11	CADM1, MAL, and miR124 Promoter Methylation as Biomarkers of Transforming Cervical Intrapithelial Lesions.Int J Mol Sci. 2019 May 7;20(9):2262. doi: 10.3390/ijms20092262.
12	The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model.J Clin Invest. 2009 Apr;119(4):852-64. doi: 10.1172/JCI35901. Epub 2009 Mar 16.
13	MAL is expressed in a subset of Hodgkin lymphoma and identifies a population of patients with poor prognosis.Am J Clin Pathol. 2006 May;125(5):776-82. doi: 10.1309/98KL-HRDA-M5CM-DHE2.
14	CADM1, MAL and miR124-2 methylation analysis in cervical scrapes to detect cervical and endometrial cancer.J Clin Pathol. 2014 Dec;67(12):1067-71. doi: 10.1136/jclinpath-2014-202616. Epub 2014 Oct 3.
15	Loss of MAL expression in precancerous lesions of the esophagus.Ann Surg Oncol. 2007 May;14(5):1670-7. doi: 10.1245/s10434-006-9064-2. Epub 2006 Dec 6.
16	Enhanced expression of 2,3-linked sialic acids promotes gastric cancer cell metastasis and correlates with poor prognosis.Int J Oncol. 2017 Apr;50(4):1201-1210. doi: 10.3892/ijo.2017.3882. Epub 2017 Feb 20.
17	T-lymphocyte maturation-associated protein gene as a candidate metastasis suppressor for head and neck squamous cell carcinomas.Cancer Sci. 2009 May;100(5):873-80. doi: 10.1111/j.1349-7006.2009.01132.x.
18	KIF1A and EDNRB are differentially methylated in primary HNSCC and salivary rinses.Int J Cancer. 2010 Nov 15;127(10):2351-9. doi: 10.1002/ijc.25248.
19	Comparison of anti-EGFR-Fab' conjugated immunoliposomes modified with two different conjugation linkers for siRNa delivery in SMMC-7721 cells.Int J Nanomedicine. 2013;8:3271-83. doi: 10.2147/IJN.S47597. Epub 2013 Aug 26.
20	Herpes Simplex Virus 1 Spread in Oligodendrocytic Cells Is Highly Dependent on MAL Proteolipid.J Virol. 2020 Jan 31;94(4):e01739-19. doi: 10.1128/JVI.01739-19. Print 2020 Jan 31.
21	The molecular basis of leukemia.Hematology Am Soc Hematol Educ Program. 2004:80-97. doi: 10.1182/asheducation-2004.1.80.
22	Global identification of genes targeted by DNMT3b for epigenetic silencing in lung cancer.Oncogene. 2015 Jan 29;34(5):621-30. doi: 10.1038/onc.2013.580. Epub 2014 Jan 27.
23	Caveolin-1 and MAL are located on prostasomes secreted by the prostate cancer PC-3 cell line.J Cell Sci. 2004 Oct 15;117(Pt 22):5343-51. doi: 10.1242/jcs.01420. Epub 2004 Oct 5.
24	An experimental investigation of a novel iron chelating protoporphyrin IX prodrug for the enhancement of photodynamic therapy.Lasers Surg Med. 2018 Jul;50(5):552-565. doi: 10.1002/lsm.22809. Epub 2018 Mar 31.
25	Effect of Methyl Aminolevulinate Photodynamic Therapy With and Without Ablative Fractional Laser Treatment in Patients With Microinvasive Squamous Cell Carcinoma: A Randomized Clinical Trial.JAMA Dermatol. 2017 Mar 1;153(3):289-295. doi: 10.1001/jamadermatol.2016.4463.
26	Elevated MAL expression is accompanied by promoter hypomethylation and platinum resistance in epithelial ovarian cancer.Int J Cancer. 2010 Mar 15;126(6):1378-89. doi: 10.1002/ijc.24797.
27	MAL promoter hypermethylation as a novel prognostic marker in gastric cancer.Br J Cancer. 2008 Dec 2;99(11):1802-7. doi: 10.1038/sj.bjc.6604777. Epub 2008 Nov 11.
28	An Efficient Bivalent Cyclic RGD-PIK3CB siRNA Conjugate for Specific Targeted Therapy against Glioblastoma InVitro and InVivo.Mol Ther Nucleic Acids. 2018 Dec 7;13:220-232. doi: 10.1016/j.omtn.2018.09.002. Epub 2018 Sep 6.
29	Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-talk between MyD88 and FAK pathways.J Immunol. 2008 Mar 1;180(5):3485-91. doi: 10.4049/jimmunol.180.5.3485.
30	A Revised Motor Activity Log Following Rasch Validation (Rasch-Based MAL-18) and Consensus Methods in Chronic Stroke and Multiple Sclerosis.Neurorehabil Neural Repair. 2019 Oct;33(10):787-791. doi: 10.1177/1545968319868717. Epub 2019 Aug 18.
31	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.
32	Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
33	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.
34	Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
35	Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy. Mol Cancer Res. 2009 Feb;7(2):199-209. doi: 10.1158/1541-7786.MCR-08-0314. Epub 2009 Feb 10.
36	In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
37	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.
38	Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
39	Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
40	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.
41	Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
42	Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
43	Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.