General Information of Drug Off-Target (DOT) (ID: OTYI2WNS)

DOT Name M-phase phosphoprotein 8 (MPHOSPH8)
Synonyms Two hybrid-associated protein 3 with RanBPM; Twa3
Gene Name MPHOSPH8
Related Disease
Advanced cancer ( )
Colorectal carcinoma ( )
Gastric cancer ( )
Gastric neoplasm ( )
Non-small-cell lung cancer ( )
Stomach cancer ( )
Neoplasm ( )
UniProt ID
MPP8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3LWE; 3QO2; 3R93; 3SVM; 6V2S; 7M5U
Pfam ID
PF00023 ; PF12796 ; PF00385
Sequence
MEQVAEGARVTAVPVSAADSTEELAEVEEGVGVVGEDNDAAARGAEAFGDSEEDGEDVFE
VEKILDMKTEGGKVLYKVRWKGYTSDDDTWEPEIHLEDCKEVLLEFRKKIAENKAKAVRK
DIQRLSLNNDIFEANSDSDQQSETKEDTSPKKKKKKLRQREEKSPDDLKKKKAKAGKLKD
KSKPDLESSLESLVFDLRTKKRISEAKEELKESKKPKKDEVKETKELKKVKKGEIRDLKT
KTREDPKENRKTKKEKFVESQVESESSVLNDSPFPEDDSEGLHSDSREEKQNTKSARERA
GQDMGLEHGFEKPLDSAMSAEEDTDVRGRRKKKTPRKAEDTRENRKLENKNAFLEKKTVP
KKQRNQDRSKSAAELEKLMPVSAQTPKGRRLSGEERGLWSTDSAEEDKETKRNESKEKYQ
KRHDSDKEEKGRKEPKGLKTLKEIRNAFDLFKLTPEEKNDVSENNRKREEIPLDFKTIDD
HKTKENKQSLKERRNTRDETDTWAYIAAEGDQEVLDSVCQADENSDGRQQILSLGMDLQL
EWMKLEDFQKHLDGKDENFAATDAIPSNVLRDAVKNGDYITVKVALNSNEEYNLDQEDSS
GMTLVMLAAAGGQDDLLRLLITKGAKVNGRQKNGTTALIHAAEKNFLTTVAILLEAGAFV
NVQQSNGETALMKACKRGNSDIVRLVIECGADCNILSKHQNSALHFAKQSNNVLVYDLLK
NHLETLSRVAEETIKDYFEARLALLEPVFPIACHRLCEGPDFSTDFNYKPPQNIPEGSGI
LLFIFHANFLGKEVIARLCGPCSVQAVVLNDKFQLPVFLDSHFVYSFSPVAGPNKLFIRL
TEAPSAKVKLLIGAYRVQLQ
Function
Heterochromatin component that specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression. Mediates recruitment of the HUSH complex to H3K9me3 sites: the HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2. Binds H3K9me and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene. Mediates down-regulation of CDH1 expression. Also represses L1 retrotransposons in collaboration with MORC2 and, probably, SETDB1, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression. The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [2]
Gastric cancer DISXGOUK Strong Altered Expression [3]
Gastric neoplasm DISOKN4Y Strong Biomarker [3]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [1]
Stomach cancer DISKIJSX Strong Altered Expression [3]
Neoplasm DISZKGEW Limited Altered Expression [3]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 M-phase phosphoprotein 8 (MPHOSPH8). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of M-phase phosphoprotein 8 (MPHOSPH8). [5]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of M-phase phosphoprotein 8 (MPHOSPH8). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of M-phase phosphoprotein 8 (MPHOSPH8). [7]
Marinol DM70IK5 Approved Marinol increases the expression of M-phase phosphoprotein 8 (MPHOSPH8). [8]
Amphotericin B DMTAJQE Approved Amphotericin B decreases the expression of M-phase phosphoprotein 8 (MPHOSPH8). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of M-phase phosphoprotein 8 (MPHOSPH8). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of M-phase phosphoprotein 8 (MPHOSPH8). [12]
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⏷ Show the Full List of 8 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of M-phase phosphoprotein 8 (MPHOSPH8). [11]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of M-phase phosphoprotein 8 (MPHOSPH8). [11]
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References

1 Knockdown of MPP8 suppresses cell proliferation via regulation of HOXA5 in non-small cell lung cancer cells.Cell Mol Biol (Noisy-le-grand). 2018 Jan 31;64(1):27-31. doi: 10.14715/cmb/2018.64.1.6.
2 Lentivirus-mediated knockdown of M-phase phosphoprotein 8 inhibits proliferation of colon cancer cells.Biotechnol Appl Biochem. 2017 Nov;64(6):911-917. doi: 10.1002/bab.1504. Epub 2017 Sep 7.
3 M-phase phosphoprotein 8 promotes gastric cancer growth and metastasis via p53/Bcl-2 and EMT-related signaling pathways.J Cell Biochem. 2020 Mar;121(3):2330-2342. doi: 10.1002/jcb.29456. Epub 2019 Nov 6.
4 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
5 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
6 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
7 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.
8 Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
9 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
10 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
11 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
12 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.