General Information of Drug Off-Target (DOT) (ID: OTQF0JPY)

DOT Name Leishmanolysin-like peptidase (LMLN)
Synonyms EC 3.4.24.-; Invadolysin
Gene Name LMLN
Related Disease
Cutaneous leishmaniasis ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Intellectual disability ( )
Thyroid gland papillary carcinoma ( )
Advanced cancer ( )
Amyotrophic lateral sclerosis ( )
Benign prostatic hyperplasia ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma ( )
Clear cell renal carcinoma ( )
Colorectal carcinoma ( )
Ductal breast carcinoma in situ ( )
Endometriosis ( )
Familial amyotrophic lateral sclerosis ( )
Gastric cancer ( )
Head-neck squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
Invasive ductal breast carcinoma ( )
Leukemia ( )
Lung cancer ( )
Lung carcinoma ( )
Neoplasm ( )
Pancreatic cancer ( )
Periodontitis ( )
Prostate neoplasm ( )
Schizophrenia ( )
Stomach cancer ( )
Bone osteosarcoma ( )
Melanoma ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Plasmodium falciparum malaria ( )
Prostate carcinoma ( )
Squamous cell carcinoma ( )
Visceral leishmaniasis ( )
Rheumatoid arthritis ( )
Acute myelogenous leukaemia ( )
Adenocarcinoma ( )
Adult glioblastoma ( )
Leishmaniasis ( )
Mucocutaneous leishmaniasis ( )
Nasopharyngeal carcinoma ( )
Prostate cancer ( )
Renal cell carcinoma ( )
UniProt ID
LMLN_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
3.4.24.-
Pfam ID
PF01457
Sequence
MAAEWGGGVGYSGSGPGRSRWRWSGSVWVRSVLLLLGGLRASATSTPVSLGSSPPCRHHV
PSDTEVINKVHLKANHVVKRDVDEHLRIKTVYDKSVEELLPEKKNLVKNKLFPQAISYLE
KTFQVRRPAGTILLSRQCATNQYLRKENDPHRYCTGECAAHTKCGPVIVPEEHLQQCRVY
RGGKWPHGAVGVPDQEGISDADFVLYVGALATERCSHENIISYAAYCQQEANMDRPIAGY
ANLCPNMISTQPQEFVGMLSTVKHEVIHALGFSAGLFAFYHDKDGNPLTSRFADGLPPFN
YSLGLYQWSDKVVRKVERLWDVRDNKIVRHTVYLLVTPRVVEEARKHFDCPVLEGMELEN
QGGVGTELNHWEKRLLENEAMTGSHTQNRVLSRITLALMEDTGRQMLSPYCDTLRSNPLQ
LTCRQDQRAVAVCNLQKFPKPLPQEYQYFDELSGIPAEDLPYYGGSVEIADYCPFSQEFS
WHLSGEYQRSSDCRILENQPEIFKNYGAEKYGPHSVCLIQKSAFVMEKCERKLSYPDWGS
GCYQVSCSPQGLKVWVQDTSYLCSRAGQVLPVSIQMNGWIHDGNLLCPSCWDFCELCPPE
TDPPATNLTRALPLDLCSCSSSLVVTLWLLLGNLFPLLAGFLLCIWH
Function Metalloprotease.
Tissue Specificity Expressed in all cell lines analyzed.

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cutaneous leishmaniasis DISRK7TS Definitive Altered Expression [1]
Epithelial ovarian cancer DIS56MH2 Definitive Biomarker [2]
Esophageal squamous cell carcinoma DIS5N2GV Definitive Biomarker [3]
Intellectual disability DISMBNXP Definitive Biomarker [4]
Thyroid gland papillary carcinoma DIS48YMM Definitive Posttranslational Modification [5]
Advanced cancer DISAT1Z9 Strong Biomarker [6]
Amyotrophic lateral sclerosis DISF7HVM Strong Biomarker [7]
Benign prostatic hyperplasia DISI3CW2 Strong Biomarker [8]
Breast cancer DIS7DPX1 Strong Biomarker [9]
Breast carcinoma DIS2UE88 Strong Biomarker [9]
Breast neoplasm DISNGJLM Strong Biomarker [9]
Carcinoma DISH9F1N Strong Posttranslational Modification [10]
Clear cell renal carcinoma DISBXRFJ Strong Biomarker [11]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [12]
Ductal breast carcinoma in situ DISLCJY7 Strong Genetic Variation [13]
Endometriosis DISX1AG8 Strong Biomarker [14]
Familial amyotrophic lateral sclerosis DISWZ9CJ Strong Genetic Variation [15]
Gastric cancer DISXGOUK Strong Posttranslational Modification [16]
Head-neck squamous cell carcinoma DISF7P24 Strong Posttranslational Modification [17]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [18]
Invasive ductal breast carcinoma DIS43J58 Strong Biomarker [19]
Leukemia DISNAKFL Strong Biomarker [20]
Lung cancer DISCM4YA Strong Posttranslational Modification [21]
Lung carcinoma DISTR26C Strong Posttranslational Modification [21]
Neoplasm DISZKGEW Strong Posttranslational Modification [22]
Pancreatic cancer DISJC981 Strong Posttranslational Modification [23]
Periodontitis DISI9JOI Strong Biomarker [24]
Prostate neoplasm DISHDKGQ Strong Posttranslational Modification [25]
Schizophrenia DISSRV2N Strong Biomarker [26]
Stomach cancer DISKIJSX Strong Posttranslational Modification [16]
Bone osteosarcoma DIST1004 moderate Biomarker [27]
Melanoma DIS1RRCY moderate Biomarker [28]
Non-small-cell lung cancer DIS5Y6R9 moderate Biomarker [29]
Osteosarcoma DISLQ7E2 moderate Biomarker [27]
Plasmodium falciparum malaria DIS3Q9KF moderate Biomarker [30]
Prostate carcinoma DISMJPLE moderate Biomarker [31]
Squamous cell carcinoma DISQVIFL moderate Biomarker [32]
Visceral leishmaniasis DISTKEYK moderate Genetic Variation [33]
Rheumatoid arthritis DISTSB4J Disputed Altered Expression [34]
Acute myelogenous leukaemia DISCSPTN Limited Biomarker [35]
Adenocarcinoma DIS3IHTY Limited Posttranslational Modification [36]
Adult glioblastoma DISVP4LU Limited Posttranslational Modification [37]
Leishmaniasis DISABTW7 Limited Biomarker [38]
Mucocutaneous leishmaniasis DISQEME2 Limited Altered Expression [1]
Nasopharyngeal carcinoma DISAOTQ0 Limited Posttranslational Modification [39]
Prostate cancer DISF190Y Limited Biomarker [31]
Renal cell carcinoma DISQZ2X8 Limited Posttranslational Modification [40]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 Leishmanolysin-like peptidase (LMLN). [41]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Leishmanolysin-like peptidase (LMLN). [42]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Leishmanolysin-like peptidase (LMLN). [43]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Leishmanolysin-like peptidase (LMLN). [44]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Leishmanolysin-like peptidase (LMLN). [46]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Leishmanolysin-like peptidase (LMLN). [47]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Leishmanolysin-like peptidase (LMLN). [48]
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⏷ Show the Full List of 7 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 decreases the methylation of Leishmanolysin-like peptidase (LMLN). [45]
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References

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2 Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk.PLoS One. 2015 Jun 19;10(6):e0128106. doi: 10.1371/journal.pone.0128106. eCollection 2015.
3 MSH2 promoter hypermethylation in circulating tumor DNA is a valuable predictor of disease-free survival for patients with esophageal squamous cell carcinoma.Eur J Surg Oncol. 2012 Apr;38(4):326-32. doi: 10.1016/j.ejso.2012.01.008. Epub 2012 Jan 23.
4 Pharmacotherapy for mood and anxiety disorders in older people with intellectual disability in comparison with the general population.BMC Psychiatry. 2019 Aug 1;19(1):238. doi: 10.1186/s12888-019-2191-7.
5 Aberrant hypermethylation of the HOXD10 gene in papillary thyroid cancer with BRAFV600E mutation.Oncol Rep. 2018 Jan;39(1):338-348. doi: 10.3892/or.2017.6058. Epub 2017 Oct 25.
6 Inhibition of MSP-RON signaling pathway in cancer cells by a novel soluble form of RON comprising the entire sema sequence.Int J Oncol. 2010 Jun;36(6):1551-61. doi: 10.3892/ijo_00000642.
7 VAMP associated proteins are required for autophagic and lysosomal degradation by promoting a PtdIns4P-mediated endosomal pathway.Autophagy. 2019 Jul;15(7):1214-1233. doi: 10.1080/15548627.2019.1580103. Epub 2019 Feb 20.
8 SFRP1 repression in prostate cancer is triggered by two different epigenetic mechanisms.Gene. 2016 Nov 30;593(2):292-301. doi: 10.1016/j.gene.2016.08.030. Epub 2016 Aug 26.
9 ESR1 Methylation: A Liquid Biopsy-Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment.Clin Cancer Res. 2018 Mar 15;24(6):1500-1510. doi: 10.1158/1078-0432.CCR-17-1181. Epub 2017 Dec 28.
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11 Methylation of the gamma-catenin gene is associated with poor prognosis of renal cell carcinoma.Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):557-64.
12 Epigenetic silencing of ADAMTS5 is associated with increased invasiveness and poor survival in patients with colorectal cancer.J Cancer Res Clin Oncol. 2018 Feb;144(2):215-227. doi: 10.1007/s00432-017-2545-9. Epub 2017 Nov 15.
13 Differences in Breast Cancer Characteristics by Mammography Screening Participation or Non-Participation.Dtsch Arztebl Int. 2018 Aug 6;115(31-32):520-527. doi: 10.3238/arztebl.2018.0520.
14 The macrophage stimulating protein/RON system: a potential novel target for prevention and treatment of endometriosis.Mol Hum Reprod. 2005 May;11(5):345-9. doi: 10.1093/molehr/gah162. Epub 2005 Mar 11.
15 Structural, stability, dynamic and binding properties of the ALS-causing T46I mutant of the hVAPB MSP domain as revealed by NMR and MD simulations.PLoS One. 2011;6(11):e27072. doi: 10.1371/journal.pone.0027072. Epub 2011 Nov 1.
16 DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer.Gastric Cancer. 2017 Sep;20(5):784-792. doi: 10.1007/s10120-017-0697-6. Epub 2017 Feb 27.
17 Dysregulated miR-363 affects head and neck cancer invasion and metastasis by targeting podoplanin.Int J Biochem Cell Biol. 2013 Mar;45(3):513-20. doi: 10.1016/j.biocel.2012.12.004. Epub 2012 Dec 12.
18 Frequent methylation of HOXA9 gene in tumor tissues and plasma samples from human hepatocellular carcinomas.Clin Chem Lab Med. 2014 Aug;52(8):1235-45. doi: 10.1515/cclm-2013-0780.
19 Pharmacologic reversion of epigenetic silencing of the PRKD1 promoter blocks breast tumor cell invasion and metastasis.Breast Cancer Res. 2013 Aug 23;15(2):R66. doi: 10.1186/bcr3460.
20 INV(12) (p13q11) and dicentric chromosomes in a secondary leukaemia with basophilia.Haematologica. 1990 Sep-Oct;75(5):473-6.
21 Abnormal hypermethylation and clinicopathological significance of Axin gene in lung cancer.Tumour Biol. 2013 Apr;34(2):749-57. doi: 10.1007/s13277-012-0604-z. Epub 2012 Nov 29.
22 RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.Oncotarget. 2017 Mar 28;8(13):21429-21443. doi: 10.18632/oncotarget.15249.
23 Expression of DNMT1 and DNMT3a are regulated by GLI1 in human pancreatic cancer.PLoS One. 2011;6(11):e27684. doi: 10.1371/journal.pone.0027684. Epub 2011 Nov 14.
24 Relationship between severity of periodontitis and masseter muscle activity during waking and sleeping hours.Arch Oral Biol. 2018 Jun;90:13-18. doi: 10.1016/j.archoralbio.2018.02.021. Epub 2018 Mar 1.
25 DNA-based detection of prostate cancer in blood, urine, and ejaculates.Ann N Y Acad Sci. 2001 Sep;945:51-8. doi: 10.1111/j.1749-6632.2001.tb03863.x.
26 Comparative linkage meta-analysis reveals regionally-distinct, disparate genetic architectures: application to bipolar disorder and schizophrenia.PLoS One. 2011 Apr 29;6(4):e19073. doi: 10.1371/journal.pone.0019073.
27 MSP-4, an antimicrobial peptide, induces apoptosis via activation of extrinsic Fas/FasL- and intrinsic mitochondria-mediated pathways in one osteosarcoma cell line. Mar Drugs. 2018 Jan 2;16(1).
28 Comprehensive analysis of receptor tyrosine kinase activation in human melanomas reveals autocrine signaling through IGF-1R.Melanoma Res. 2011 Aug;21(4):274-84. doi: 10.1097/CMR.0b013e328343a1d6.
29 Role of transcription factor FOXA1 in nonsmall cell lung cancer.Mol Med Rep. 2018 Jan;17(1):509-521. doi: 10.3892/mmr.2017.7885. Epub 2017 Oct 26.
30 Variant-specific antibodies to merozoite surface protein 2 and clinical expression of Plasmodium falciparum malaria in rural Amazonians.Am J Trop Med Hyg. 2007 Jun;76(6):1084-91.
31 An exome-wide rare variant analysis of Korean men identifies three novel genes predisposing to prostate cancer.Sci Rep. 2019 Nov 20;9(1):17173. doi: 10.1038/s41598-019-53445-2.
32 Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas.Respir Res. 2014 Dec 31;15(1):160. doi: 10.1186/s12931-014-0160-8.
33 Genetic homogeneity among Leishmania (Leishmania) infantum isolates from dog and human samples in Belo Horizonte Metropolitan Area (BHMA), Minas Gerais, Brazil.Parasit Vectors. 2015 Apr 15;8:226. doi: 10.1186/s13071-015-0837-y.
34 Identification of pathogenic genes related to rheumatoid arthritis through integrated analysis of DNA methylation and gene expression profiling.Gene. 2017 Nov 15;634:62-67. doi: 10.1016/j.gene.2017.08.032. Epub 2017 Sep 4.
35 Quantification of CBFbeta/MYH11 fusion transcript by real time RT-PCR in patients with INV(16) acute myeloid leukemia.Leukemia. 2001 Jul;15(7):1072-80. doi: 10.1038/sj.leu.2402159.
36 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.
37 Real-Time Methylation-Specific Polymerase Chain Reaction for MGMT Promoter Methylation Clinical Testing in Glioblastoma: An Alternative Detection Method for a Heterogeneous Process.Am J Clin Pathol. 2017 Oct 1;148(4):296-307. doi: 10.1093/ajcp/aqx073.
38 Extracellular release of virulence factor major surface protease via exosomes in Leishmania infantum promastigotes.Parasit Vectors. 2018 Jun 19;11(1):355. doi: 10.1186/s13071-018-2937-y.
39 The new 6q27 tumor suppressor DACT2, frequently silenced by CpG methylation, sensitizes nasopharyngeal cancer cells to paclitaxel and 5-FU toxicity via -catenin/Cdc25c signaling and G2/M arrest.Clin Epigenetics. 2018 Feb 27;10(1):26. doi: 10.1186/s13148-018-0459-2.
40 The Silencing of CCND2 by Promoter Aberrant Methylation in Renal Cell Cancer and Analysis of the Correlation between CCND2 Methylation Status and Clinical Features.PLoS One. 2016 Sep 1;11(9):e0161859. doi: 10.1371/journal.pone.0161859. eCollection 2016.
41 The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
42 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.
43 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.
44 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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46 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
47 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
48 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.