Details of Drug Off-Target (DOT)

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

• DOT Name: Cartilage matrix protein (MATN1)
• Synonyms: Matrilin-1
• Gene Name: MATN1
• Related Disease:
  Amyloidosis
  Androgen insensitivity syndrome
  Atrichia with papular lesions
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Cardiomyopathy
  Coagulation defect
  Colon carcinoma
  Colorectal carcinoma
  Congestive heart failure
  Gonorrhea
  Hypopigmentation of the skin
  Intellectual disability
  Melanoma
  Neuralgia
  Salla disease
  Sialuria
  Triple negative breast cancer
  Achondrogenesis type II
  Autosomal dominant prognathism
  Influenza
  Osteochondrodysplasia
  Skeletal dysplasia
  Acute myelogenous leukaemia
  Promyelocytic leukaemia
• UniProt ID: MATN1_HUMAN
• Pfam ID: PF14670 ; PF10393 ; PF00092
• Sequence:
  MRVLSGTSLMLCSLLLLLQALCSPGLAPQSRGHLCRTRPTDLVFVVDSSRSVRPVEFEKV
  KVFLSQVIESLDVGPNATRVGMVNYASTVKQEFSLRAHVSKAALLQAVRRIQPLSTGTMT
  GLAIQFAITKAFGDAEGGRSRSPDISKVVIVVTDGRPQDSVQDVSARARASGVELFAIGV
  GSVDKATLRQIASEPQDEHVDYVESYSVIEKLSRKFQEAFCVVSDLCATGDHDCEQVCIS
  SPGSYTCACHEGFTLNSDGKTCNVCSGGGGSSATDLVFLIDGSKSVRPENFELVKKFISQ
  IVDTLDVSDKLAQVGLVQYSSSVRQEFPLGRFHTKKDIKAAVRNMSYMEKGTMTGAALKY
  LIDNSFTVSSGARPGAQKVGIVFTDGRSQDYINDAAKKAKDLGFKMFAVGVGNAVEDELR
  EIASEPVAEHYFYTADFKTINQIGKKLQKKICVEEDPCACESLVKFQAKVEGLLQALTRK
  LEAVSKRLAILENTVV
• Function: Cartilage matrix protein is a major component of the extracellular matrix of non-articular cartilage. It binds to collagen.
• Reactome Pathway: ECM proteoglycans (R-HSA-3000178)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyloidosis	DISHTAI2	Strong	Altered Expression	[1]
Androgen insensitivity syndrome	DISUZBBO	Strong	Genetic Variation	[2]
Atrichia with papular lesions	DIS80CUB	Strong	Biomarker	[3]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cardiac failure	DISDC067	Strong	Biomarker	[6]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[3]
Coagulation defect	DIS9X3H6	Strong	Biomarker	[7]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[6]
Gonorrhea	DISQ5AO6	Strong	Biomarker	[10]
Hypopigmentation of the skin	DIS39YKC	Strong	Genetic Variation	[11]
Intellectual disability	DISMBNXP	Strong	Biomarker	[7]
Melanoma	DIS1RRCY	Strong	Altered Expression	[12]
Neuralgia	DISWO58J	Strong	Genetic Variation	[13]
Salla disease	DISA4PBW	Strong	Biomarker	[14]
Sialuria	DISK9T5J	Strong	Biomarker	[14]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[15]
Achondrogenesis type II	DIS7IMR5	moderate	Genetic Variation	[16]
Autosomal dominant prognathism	DIS2G3FF	moderate	Genetic Variation	[17]
Influenza	DIS3PNU3	moderate	Biomarker	[18]
Osteochondrodysplasia	DIS9SPWW	moderate	Genetic Variation	[16]
Skeletal dysplasia	DIS5Z8U6	moderate	Genetic Variation	[16]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[19]
Promyelocytic leukaemia	DISYGG13	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cartilage matrix protein (MATN1).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cartilage matrix protein (MATN1).	[25]

4 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 Cartilage matrix protein (MATN1).	[21]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cartilage matrix protein (MATN1).	[22]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cartilage matrix protein (MATN1).	[23]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Cartilage matrix protein (MATN1).	[24]

References

• [1] Matrix metalloproteinases and their tissue inhibitors in cardiac amyloidosis: relationship to structural, functional myocardial changes and to light chain amyloid deposition.Circ Heart Fail. 2008 Nov;1(4):249-57. doi: 10.1161/CIRCHEARTFAILURE.108.788687. Epub 2008 Oct 14.
• [2] The association of rs1149048 polymorphism in matrilin-1(MATN1) gene with adolescent idiopathic scoliosis susceptibility: a meta-analysis.Mol Biol Rep. 2014;41(4):2543-9. doi: 10.1007/s11033-014-3112-y. Epub 2014 Jan 28.
• [3] Assessment of late cardiomyopathy by magnetic resonance imaging in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and idarubicin.Ann Hematol. 2017 Jul;96(7):1077-1084. doi: 10.1007/s00277-017-3004-z. Epub 2017 Apr 28.
• [4] alpha2,3-sialyltransferase mRNA and alpha2,3-linked glycoprotein sialylation are increased in malignant gliomas.Brain Res. 1997 Apr 25;755(1):175-9. doi: 10.1016/s0006-8993(97)00241-2.
• [5] Expression of sialyl-Tn antigen in breast cancer cells transfected with the human CMP-Neu5Ac: GalNAc alpha2,6-sialyltransferase (ST6GalNac I) cDNA.Glycoconj J. 2001 Nov-Dec;18(11-12):883-93. doi: 10.1023/a:1022200525695.
• [6] The challenge of cardiomyopathies and heart failure in pregnancy.Curr Opin Obstet Gynecol. 2018 Dec;30(6):378-384. doi: 10.1097/GCO.0000000000000496.
• [7] Intellectual disability and bleeding diathesis due to deficient CMP--sialic acid transport.Neurology. 2013 Aug 13;81(7):681-7. doi: 10.1212/WNL.0b013e3182a08f53. Epub 2013 Jul 19.
• [8] Characterization of two glycolipid: alpha 2-3sialyltransferases, SAT-3 (CMP-NeuAc:nLcOse4Cer alpha 2-3sialyltransferase) and SAT-4 (CMP-NeuAc:GgOse4Cer alpha 2-3sialyltransferase), from human colon carcinoma (Colo 205) cell line.Biochemistry. 1996 Apr 23;35(16):5166-74. doi: 10.1021/bi960239l.
• [9] Elevation of ST6Gal I activity in malignant and transitional tissue in human colorectal cancer.Oncology. 2005;69(5):436-44. doi: 10.1159/000089999. Epub 2005 Nov 25.
• [10] Utilizing complement evasion strategies to design complement-based antibacterial immunotherapeutics: Lessons from the pathogenic Neisseriae.Immunobiology. 2016 Oct;221(10):1110-23. doi: 10.1016/j.imbio.2016.05.016. Epub 2016 Jun 1.
• [11] Candida albicans quorum-sensing molecule farnesol modulates staphyloxanthin production and activates the thiol-based oxidative-stress response in Staphylococcus aureus.Virulence. 2019 Dec;10(1):625-642. doi: 10.1080/21505594.2019.1635418.
• [12] Expression of the human CMP-NeuAc:GM3 alpha2,8-sialyltransferase (GD3 synthase) gene through the NF-kappaB activation in human melanoma SK-MEL-2 cells.Biochim Biophys Acta. 2007 Nov-Dec;1769(11-12):622-30. doi: 10.1016/j.bbaexp.2007.08.001. Epub 2007 Aug 25.
• [13] A double-blind, randomized, comparative study of the use of a combination of uridine triphosphate trisodium, cytidine monophosphate disodium, and hydroxocobalamin, versus isolated treatment with hydroxocobalamin, in patients presenting with compressive neuralgias.J Pain Res. 2017 Feb 15;10:397-404. doi: 10.2147/JPR.S123045. eCollection 2017.
• [14] Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis.Biol Chem. 2009 Jul;390(7):591-9. doi: 10.1515/BC.2009.073.
• [15] Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients.Sci Rep. 2016 Aug 25;6:32027. doi: 10.1038/srep32027.
• [16] Matrix composition of cartilaginous anlagen in achondrogenesis type II (Langer-Saldino).Front Biosci. 2005 Jan 1;10:446-53. doi: 10.2741/1540. Print 2005 Jan 1.
• [17] Polymorphisms in the Matrilin-1 gene and risk of mandibular prognathism in Koreans.J Dent Res. 2010 Nov;89(11):1203-7. doi: 10.1177/0022034510375962. Epub 2010 Aug 25.
• [18] Ultrasensitive Electrical Detection of Hemagglutinin for Point-of-Care Detection of Influenza Virus Based on a CMP-NANA Probe and Top-Down Processed Silicon Nanowire Field-Effect Transistors.Sensors (Basel). 2019 Oct 17;19(20):4502. doi: 10.3390/s19204502.
• [19] The prognostic value of cN-II and cN-III enzymes in adult acute myeloid leukemia.Haematologica. 2005 Dec;90(12):1699-701.
• [20] 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.
• [21] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [22] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [23] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [24] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [25] 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.