Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9QIHEQ)

DOT Name Reversion-inducing cysteine-rich protein with Kazal motifs (RECK)
Synonyms hRECK; Suppressor of tumorigenicity 15 protein
Gene Name RECK
UniProt ID
RECK_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
8TZP
Pfam ID
PF07648
Sequence
MATVRASLRGALLLLLAVAGVAEVAGGLAPGSAGALCCNHSKDNQMCRDVCEQIFSSKSE
SRLKHLLQRAPDYCPETMVEIWNCMNSSLPGVFKKSDGWVGLGCCELAIALECRQACKQA
SSKNDISKVCRKEYENALFSCISRNEMGSVCCSYAGHHTNCREYCQAIFRTDSSPGPSQI
KAVENYCASISPQLIHCVNNYTQSYPMRNPTDSLYCCDRAEDHACQNACKRILMSKKTEM
EIVDGLIEGCKTQPLPQDPLWQCFLESSQSVHPGVTVHPPPSTGLDGAKLHCCSKANTST
CRELCTKLYSMSWGNTQSWQEFDRFCEYNPVEVSMLTCLADVREPCQLGCRNLTYCTNFN
NRPTELFRSCNAQSDQGAMNDMKLWEKGSIKMPFINIPVLDIKKCQPEMWKAIACSLQIK
PCHSKSRGSIICKSDCVEILKKCGDQNKFPEDHTAESICELLSPTDDLKNCIPLDTYLRP
STLGNIVEEVTHPCNPNPCPANELCEVNRKGCPSGDPCLPYFCVQGCKLGEASDFIVRQG
TLIQVPSSAGEVGCYKICSCGQSGLLENCMEMHCIDLQKSCIVGGKRKSHGTSFSIDCNV
CSCFAGNLVCSTRLCLSEHSSEDDRRTFTGLPCNCADQFVPVCGQNGRTYPSACIARCVG
LQDHQFEFGSCMSKDPCNPNPCQKNQRCIPKPQVCLTTFDKFGCSQYECVPRQLACDQVQ
DPVCDTDHMEHNNLCTLYQRGKSLSYKGPCQPFCRATEPVCGHNGETYSSVCAAYSDRVA
VDYYGDCQAVGVLSEHSSVAECASVKCPSLLAAGCKPIIPPGACCPLCAGMLRVLFDKEK
LDTIAKVTNKKPITVLEILQKIRMHVSVPQCDVFGYFSIESEIVILIIPVDHYPKALQIE
ACNKEAEKIESLINSDSPTLASHVPLSALIISQVQVSSSVPSAGVRARPSCHSLLLPLSL
GLALHLLWTYN
Function
Functions together with ADGRA2 to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B). Plays a key role in Wnt7-specific responses: required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation. Acts as a Wnt7-specific coactivator of canonical Wnt signaling by decoding Wnt ligands: acts by interacting specifically with the disordered linker region of Wnt7, thereby conferring ligand selectivity for Wnt7. ADGRA2 is then required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex. Also acts as a serine protease inhibitor: negatively regulates matrix metalloproteinase-9 (MMP9) by suppressing MMP9 secretion and by direct inhibition of its enzymatic activity. Also inhibits metalloproteinase activity of MMP2 and MMP14 (MT1-MMP).
Tissue Specificity Expressed in various tissues and untransformed cells . It is undetectable in tumor-derived cell lines and oncogenically transformed cells .
KEGG Pathway
MicroR.s in cancer (hsa05206 )
Reactome Pathway
Post-translational modification (R-HSA-163125 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
21 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 Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [3]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [4]
Quercetin DM3NC4M Approved Quercetin increases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [5]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [6]
Selenium DM25CGV Approved Selenium decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [7]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [8]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [9]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [10]
Irinotecan DMP6SC2 Approved Irinotecan increases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [11]
Dasatinib DMJV2EK Approved Dasatinib increases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [12]
Cocaine DMSOX7I Approved Cocaine increases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [13]
Emetine DMCT2YF Approved Emetine decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [14]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [15]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [5]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [17]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [18]
Nickel chloride DMI12Y8 Investigative Nickel chloride decreases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [19]
ELLAGIC ACID DMX8BS5 Investigative ELLAGIC ACID increases the expression of Reversion-inducing cysteine-rich protein with Kazal motifs (RECK). [20]
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⏷ Show the Full List of 21 Drug(s)

References

1 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
3 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
4 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
6 Downregulation of RECK by promoter methylation correlates with lymph node metastasis in non-small cell lung cancer. Cancer Sci. 2007 Feb;98(2):169-73. doi: 10.1111/j.1349-7006.2006.00367.x.
7 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
8 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.
9 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
10 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
11 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
12 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
13 Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling. PLoS One. 2007 Nov 14;2(11):e1187. doi: 10.1371/journal.pone.0001187.
14 Emetine inhibits migration and invasion of human non-small-cell lung cancer cells via regulation of ERK and p38 signaling pathways. Chem Biol Interact. 2015 Dec 5;242:25-33. doi: 10.1016/j.cbi.2015.08.014. Epub 2015 Aug 30.
15 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.
16 Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
17 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.
18 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.
19 Nickel may contribute to EGFR mutation and synergistically promotes tumor invasion in EGFR-mutated lung cancer via nickel-induced microRNA-21 expression. Toxicol Lett. 2015 Aug 19;237(1):46-54. doi: 10.1016/j.toxlet.2015.05.019. Epub 2015 May 27.
20 Zinc-chelation contributes to the anti-angiogenic effect of ellagic acid on inhibiting MMP-2 activity, cell migration and tube formation. PLoS One. 2011 May 4;6(5):e18986. doi: 10.1371/journal.pone.0018986.