General Information of Drug Off-Target (DOT) (ID: OTIG527N)

DOT Name Laminin subunit gamma-1 (LAMC1)
Synonyms
Laminin B2 chain; Laminin-1 subunit gamma; Laminin-10 subunit gamma; Laminin-11 subunit gamma; Laminin-2 subunit gamma; Laminin-3 subunit gamma; Laminin-4 subunit gamma; Laminin-6 subunit gamma; Laminin-7 subunit gamma; Laminin-8 subunit gamma; Laminin-9 subunit gamma; S-laminin subunit gamma; S-LAM gamma
Gene Name LAMC1
Related Disease
Anaplastic astrocytoma ( )
Prostate carcinoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Aortic disorder ( )
Brain neoplasm ( )
Chronic kidney disease ( )
Colon cancer ( )
Colorectal adenocarcinoma ( )
Colorectal adenoma ( )
Colorectal cancer ( )
Colorectal cancer, susceptibility to, 1 ( )
Colorectal cancer, susceptibility to, 10 ( )
Colorectal cancer, susceptibility to, 12 ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Dandy-Walker syndrome ( )
DiGeorge syndrome ( )
Endometrial carcinoma ( )
Fuchs' endothelial dystrophy ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
Lipoid proteinosis ( )
Marfan syndrome ( )
Neoplasm ( )
Shprintzen-Goldberg syndrome ( )
Systemic lupus erythematosus ( )
Female hypogonadism ( )
Amyotrophic lateral sclerosis ( )
Cutaneous squamous cell carcinoma ( )
Prostate cancer ( )
Prostate neoplasm ( )
UniProt ID
LAMC1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5XAU; 7CEC; 8DMK
Pfam ID
PF00052 ; PF00053 ; PF00055
Sequence
MRGSHRAAPALRPRGRLWPVLAVLAAAAAAGCAQAAMDECTDEGGRPQRCMPEFVNAAFN
VTVVATNTCGTPPEEYCVQTGVTGVTKSCHLCDAGQPHLQHGAAFLTDYNNQADTTWWQS
QTMLAGVQYPSSINLTLHLGKAFDITYVRLKFHTSRPESFAIYKRTREDGPWIPYQYYSG
SCENTYSKANRGFIRTGGDEQQALCTDEFSDISPLTGGNVAFSTLEGRPSAYNFDNSPVL
QEWVTATDIRVTLNRLNTFGDEVFNDPKVLKSYYYAISDFAVGGRCKCNGHASECMKNEF
DKLVCNCKHNTYGVDCEKCLPFFNDRPWRRATAESASECLPCDCNGRSQECYFDPELYRS
TGHGGHCTNCQDNTDGAHCERCRENFFRLGNNEACSSCHCSPVGSLSTQCDSYGRCSCKP
GVMGDKCDRCQPGFHSLTEAGCRPCSCDPSGSIDECNIETGRCVCKDNVEGFNCERCKPG
FFNLESSNPRGCTPCFCFGHSSVCTNAVGYSVYSISSTFQIDEDGWRAEQRDGSEASLEW
SSERQDIAVISDSYFPRYFIAPAKFLGKQVLSYGQNLSFSFRVDRRDTRLSAEDLVLEGA
GLRVSVPLIAQGNSYPSETTVKYVFRLHEATDYPWRPALTPFEFQKLLNNLTSIKIRGTY
SERSAGYLDDVTLASARPGPGVPATWVESCTCPVGYGGQFCEMCLSGYRRETPNLGPYSP
CVLCACNGHSETCDPETGVCNCRDNTAGPHCEKCSDGYYGDSTAGTSSDCQPCPCPGGSS
CAVVPKTKEVVCTNCPTGTTGKRCELCDDGYFGDPLGRNGPVRLCRLCQCSDNIDPNAVG
NCNRLTGECLKCIYNTAGFYCDRCKDGFFGNPLAPNPADKCKACNCNLYGTMKQQSSCNP
VTGQCECLPHVTGQDCGACDPGFYNLQSGQGCERCDCHALGSTNGQCDIRTGQCECQPGI
TGQHCERCEVNHFGFGPEGCKPCDCHPEGSLSLQCKDDGRCECREGFVGNRCDQCEENYF
YNRSWPGCQECPACYRLVKDKVADHRVKLQELESLIANLGTGDEMVTDQAFEDRLKEAER
EVMDLLREAQDVKDVDQNLMDRLQRVNNTLSSQISRLQNIRNTIEETGNLAEQARAHVEN
TERLIEIASRELEKAKVAAANVSVTQPESTGDPNNMTLLAEEARKLAERHKQEADDIVRV
AKTANDTSTEAYNLLLRTLAGENQTAFEIEELNRKYEQAKNISQDLEKQAARVHEEAKRA
GDKAVEIYASVAQLSPLDSETLENEANNIKMEAENLEQLIDQKLKDYEDLREDMRGKELE
VKNLLEKGKTEQQTADQLLARADAAKALAEEAAKKGRDTLQEANDILNNLKDFDRRVNDN
KTAAEEALRKIPAINQTITEANEKTREAQQALGSAAADATEAKNKAHEAERIASAVQKNA
TSTKAEAERTFAEVTDLDNEVNNMLKQLQEAEKELKRKQDDADQDMMMAGMASQAAQEAE
INARKAKNSVTSLLSIINDLLEQLGQLDTVDLNKLNEIEGTLNKAKDEMKVSDLDRKVSD
LENEAKKQEAAIMDYNRDIEEIMKDIRNLEDIRKTLPSGCFNTPSIEKP
Function
Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
Tissue Specificity Found in the basement membranes (major component).
KEGG Pathway
PI3K-Akt sig.ling pathway (hsa04151 )
Focal adhesion (hsa04510 )
ECM-receptor interaction (hsa04512 )
Prion disease (hsa05020 )
Toxoplasmosis (hsa05145 )
Amoebiasis (hsa05146 )
Human papillomavirus infection (hsa05165 )
Pathways in cancer (hsa05200 )
Small cell lung cancer (hsa05222 )
Reactome Pathway
Laminin interactions (R-HSA-3000157 )
Non-integrin membrane-ECM interactions (R-HSA-3000171 )
ECM proteoglycans (R-HSA-3000178 )
L1CAM interactions (R-HSA-373760 )
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426 )
MET activates PTK2 signaling (R-HSA-8874081 )
Post-translational protein phosphorylation (R-HSA-8957275 )
EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665 )
Degradation of the extracellular matrix (R-HSA-1474228 )

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Anaplastic astrocytoma DISSBE0K Definitive Biomarker [1]
Prostate carcinoma DISMJPLE Definitive Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Alzheimer disease DISF8S70 Strong Altered Expression [4]
Aortic disorder DISKXISV Strong Biomarker [5]
Brain neoplasm DISY3EKS Strong Biomarker [6]
Chronic kidney disease DISW82R7 Strong Altered Expression [7]
Colon cancer DISVC52G Strong Genetic Variation [8]
Colorectal adenocarcinoma DISPQOUB Strong Genetic Variation [8]
Colorectal adenoma DISTSVHM Strong Genetic Variation [9]
Colorectal cancer DISNH7P9 Strong Genetic Variation [8]
Colorectal cancer, susceptibility to, 1 DISZ794C Strong Genetic Variation [8]
Colorectal cancer, susceptibility to, 10 DISQXMYM Strong Genetic Variation [8]
Colorectal cancer, susceptibility to, 12 DIS4FXJX Strong Genetic Variation [8]
Colorectal carcinoma DIS5PYL0 Strong Genetic Variation [8]
Colorectal neoplasm DISR1UCN Strong Genetic Variation [8]
Dandy-Walker syndrome DIS4HC6W Strong Genetic Variation [10]
DiGeorge syndrome DIST1RKO Strong Biomarker [11]
Endometrial carcinoma DISXR5CY Strong Altered Expression [12]
Fuchs' endothelial dystrophy DISL7TXC Strong Genetic Variation [13]
Glioblastoma multiforme DISK8246 Strong Altered Expression [14]
Glioma DIS5RPEH Strong Biomarker [15]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [16]
Lipoid proteinosis DISHAODY Strong Altered Expression [17]
Marfan syndrome DISVEUWZ Strong Biomarker [5]
Neoplasm DISZKGEW Strong Biomarker [16]
Shprintzen-Goldberg syndrome DISQH6P3 Strong Biomarker [11]
Systemic lupus erythematosus DISI1SZ7 Strong Genetic Variation [18]
Female hypogonadism DISWASB4 moderate Biomarker [19]
Amyotrophic lateral sclerosis DISF7HVM Limited Altered Expression [20]
Cutaneous squamous cell carcinoma DIS3LXUG Limited Altered Expression [3]
Prostate cancer DISF190Y Limited Biomarker [2]
Prostate neoplasm DISHDKGQ Limited Biomarker [21]
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⏷ Show the Full List of 33 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 4 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Methotrexate DM2TEOL Approved Laminin subunit gamma-1 (LAMC1) affects the response to substance of Methotrexate. [46]
Fluorouracil DMUM7HZ Approved Laminin subunit gamma-1 (LAMC1) affects the response to substance of Fluorouracil. [46]
Topotecan DMP6G8T Approved Laminin subunit gamma-1 (LAMC1) affects the response to substance of Topotecan. [46]
Mitoxantrone DMM39BF Approved Laminin subunit gamma-1 (LAMC1) affects the response to substance of Mitoxantrone. [46]
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23 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 Laminin subunit gamma-1 (LAMC1). [22]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Laminin subunit gamma-1 (LAMC1). [23]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Laminin subunit gamma-1 (LAMC1). [24]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Laminin subunit gamma-1 (LAMC1). [25]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Laminin subunit gamma-1 (LAMC1). [26]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Laminin subunit gamma-1 (LAMC1). [27]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Laminin subunit gamma-1 (LAMC1). [28]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Laminin subunit gamma-1 (LAMC1). [29]
Menadione DMSJDTY Approved Menadione affects the expression of Laminin subunit gamma-1 (LAMC1). [30]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Laminin subunit gamma-1 (LAMC1). [31]
Piroxicam DMTK234 Approved Piroxicam decreases the expression of Laminin subunit gamma-1 (LAMC1). [32]
Indomethacin DMSC4A7 Approved Indomethacin decreases the expression of Laminin subunit gamma-1 (LAMC1). [14]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Laminin subunit gamma-1 (LAMC1). [34]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Laminin subunit gamma-1 (LAMC1). [35]
Tamibarotene DM3G74J Phase 3 Tamibarotene decreases the expression of Laminin subunit gamma-1 (LAMC1). [24]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Laminin subunit gamma-1 (LAMC1). [37]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Laminin subunit gamma-1 (LAMC1). [38]
SB-431542 DM0YOXQ Preclinical SB-431542 increases the expression of Laminin subunit gamma-1 (LAMC1). [39]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Laminin subunit gamma-1 (LAMC1). [41]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Laminin subunit gamma-1 (LAMC1). [42]
Lithium chloride DMHYLQ2 Investigative Lithium chloride increases the expression of Laminin subunit gamma-1 (LAMC1). [43]
Butanoic acid DMTAJP7 Investigative Butanoic acid increases the expression of Laminin subunit gamma-1 (LAMC1). [44]
ORG2058 DMH1M6N Investigative ORG2058 decreases the expression of Laminin subunit gamma-1 (LAMC1). [45]
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⏷ Show the Full List of 23 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Resveratrol DM3RWXL Phase 3 Resveratrol affects the secretion of Laminin subunit gamma-1 (LAMC1). [36]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Laminin subunit gamma-1 (LAMC1). [40]
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References

1 Identification of COL1A1 as an invasionrelated gene in malignant astrocytoma.Int J Oncol. 2018 Dec;53(6):2542-2554. doi: 10.3892/ijo.2018.4568. Epub 2018 Sep 21.
2 miR-22 and miR-29a Are Members of the Androgen Receptor Cistrome Modulating LAMC1 and Mcl-1 in Prostate Cancer.Mol Endocrinol. 2015 Jul;29(7):1037-54. doi: 10.1210/me.2014-1358. Epub 2015 Jun 8.
3 miR-506 contributes to malignancy of cutaneous squamous cell carcinoma via targeting of P65 and LAMC1.Cell Cycle. 2019 Feb;18(3):333-345. doi: 10.1080/15384101.2019.1568747. Epub 2019 Jan 24.
4 Differential distribution of laminins in Alzheimer disease and normal human brain tissue.J Neurosci Res. 2002 Jul 15;69(2):243-56. doi: 10.1002/jnr.10292.
5 Analysis of oxidative stress enzymes and structural and functional proteins on human aortic tissue from different aortopathies.Oxid Med Cell Longev. 2014;2014:760694. doi: 10.1155/2014/760694. Epub 2014 Jul 1.
6 Changes in laminin isoforms associated with brain tumor invasion and angiogenesis.Front Biosci. 2006 Jan 1;11:81-8. doi: 10.2741/1781.
7 A novel biomarker of laminin turnover is associated with disease progression and mortality in chronic kidney disease.PLoS One. 2018 Oct 1;13(10):e0204239. doi: 10.1371/journal.pone.0204239. eCollection 2018.
8 Novel Common Genetic Susceptibility Loci for Colorectal Cancer.J Natl Cancer Inst. 2019 Feb 1;111(2):146-157. doi: 10.1093/jnci/djy099.
9 Discovery of common and rare genetic risk variants for colorectal cancer.Nat Genet. 2019 Jan;51(1):76-87. doi: 10.1038/s41588-018-0286-6. Epub 2018 Dec 3.
10 Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant Dandy-Walker malformation and occipital cephaloceles.Hum Mutat. 2013 Aug;34(8):1075-9. doi: 10.1002/humu.22351. Epub 2013 May 28.
11 Isolation of a novel gene from the DiGeorge syndrome critical region with homology to Drosophila gdl and to human LAMC1 genes.Hum Mol Genet. 1996 May;5(5):633-8. doi: 10.1093/hmg/5.5.633.
12 Laminin C1 expression by uterine carcinoma cells is associated with tumor progression.Gynecol Oncol. 2015 Nov;139(2):338-44. doi: 10.1016/j.ygyno.2015.08.025. Epub 2015 Sep 3.
13 Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy.Nat Commun. 2017 Mar 30;8:14898. doi: 10.1038/ncomms14898.
14 The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma1 in human glioblastoma cells. Exp Cell Res. 2005 Jan 15;302(2):244-52. doi: 10.1016/j.yexcr.2004.09.021.
15 High LAMC1 expression in glioma is associated with poor prognosis.Onco Targets Ther. 2019 May 29;12:4253-4260. doi: 10.2147/OTT.S205333. eCollection 2019.
16 Lamc1 promotes the Warburg effect in hepatocellular carcinoma cells by regulating PKM2 expression through AKT pathway.Cancer Biol Ther. 2019;20(5):711-719. doi: 10.1080/15384047.2018.1564558. Epub 2019 Feb 12.
17 Expression of basement membrane zone genes coding for type IV procollagen and laminin by human skin fibroblasts in vitro: elevated alpha 1 (IV) collagen mRNA levels in lipoid proteinosis.J Invest Dermatol. 1988 May;90(5):734-8. doi: 10.1111/1523-1747.ep12560934.
18 Laminin-1 (LM-111) in preeclampsia and systemic lupus erythematosus.Autoimmunity. 2013 Feb;46(1):14-20. doi: 10.3109/08916934.2012.730586. Epub 2012 Dec 3.
19 LAMC1 gene is associated with premature ovarian failure.Maturitas. 2012 Apr;71(4):402-6. doi: 10.1016/j.maturitas.2012.01.011. Epub 2012 Feb 10.
20 Selective overexpression of gamma1 laminin in astrocytes in amyotrophic lateral sclerosis indicates an involvement in ALS pathology.J Neurosci Res. 2007 Jul;85(9):2045-58. doi: 10.1002/jnr.21314.
21 Global analysis of differentially expressed genes in androgen-independent prostate cancer.Prostate Cancer Prostatic Dis. 2007;10(2):167-74. doi: 10.1038/sj.pcan.4500933. Epub 2007 Jan 2.
22 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.
23 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
24 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
25 Pretreatment of 3-MA prevents doxorubicin-induced cardiotoxicity through inhibition of autophagy initiation. Toxicology. 2023 May 15;490:153512. doi: 10.1016/j.tox.2023.153512. Epub 2023 Apr 14.
26 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
27 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
28 Gene expression profile changes in NB4 cells induced by arsenic trioxide. Acta Pharmacol Sin. 2003 Jul;24(7):646-50.
29 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.
30 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
31 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
32 Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
33 The cyclooxygenase inhibitor indomethacin modulates gene expression and represses the extracellular matrix protein laminin gamma1 in human glioblastoma cells. Exp Cell Res. 2005 Jan 15;302(2):244-52. doi: 10.1016/j.yexcr.2004.09.021.
34 Unique bisphenol A transcriptome in prostate cancer: novel effects on ERbeta expression that correspond to androgen receptor mutation status. Environ Health Perspect. 2007 Nov;115(11):1646-53. doi: 10.1289/ehp.10283.
35 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
36 Calorie restriction-induced changes in the secretome of human adipocytes, comparison with resveratrol-induced secretome effects. Biochim Biophys Acta. 2014 Sep;1844(9):1511-22. doi: 10.1016/j.bbapap.2014.04.023. Epub 2014 May 5.
37 Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
38 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
39 Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
40 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.
41 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.
42 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
43 Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
44 MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
45 The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5. Mol Endocrinol. 2010 Jul;24(7):1380-92. doi: 10.1210/me.2009-0516. Epub 2010 Jun 2.
46 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.