Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ6S50X)

• DOT Name: ER membrane protein complex subunit 10 (EMC10)
• Synonyms: Hematopoietic signal peptide-containing membrane domain-containing protein 1
• Gene Name: EMC10
• Related Disease:
  Acute myocardial infarction
  Advanced cancer
  Astrocytoma
  Cardiac failure
  Congestive heart failure
  Glioblastoma multiforme
  Glioma
  Hereditary spherocytosis
  Male infertility
  Malignant glioma
  Myocardial infarction
  Neurodevelopmental disorder with dysmorphic facies and variable seizures
  Global developmental delay with or without impaired intellectual development
• UniProt ID: EMC10_HUMAN
• PDB ID: 6WW7; 6Z3W; 7ADO; 7ADP; 8EOI; 8S9S
• Pfam ID: PF21203
• Sequence:
  MAAASAGATRLLLLLLMAVAAPSRARGSGCRAGTGARGAGAEGREGEACGTVGLLLEHSF
  EIDDSANFRKRGSLLWNQQDGTLSLSQRQLSEEERGRLRDVAALNGLYRVRIPRRPGALD
  GLEAGGYVSSFVPACSLVESHLSDQLTLHVDVAGNVVGVSVVTHPGGCRGHEVEDVDLEL
  FNTSVQLQPPTTAPGPETAAFIERLEMEQAQKAKNPQEQKSFFAKYWMYIIPVVLFLMMS
  GAPDTGGQGGGGGGGGGGGSGR
• Function: Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable). Promotes angiogenesis and tissue repair in the heart after myocardial infarction. Stimulates cardiac endothelial cell migration and outgrowth via the activation of p38 MAPK, PAK and MAPK2 signaling pathways.
• Tissue Specificity: Present in serum (at protein level). Increased expression seen in the left ventrice after myocardial infarction (at protein level). Expressed in the pituitary gland. Expressed in brain .

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Astrocytoma	DISL3V18	Strong	Biomarker	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Hereditary spherocytosis	DISQYJP5	Strong	Genetic Variation	[3]
Male infertility	DISY3YZZ	Strong	Biomarker	[4]
Malignant glioma	DISFXKOV	Strong	Genetic Variation	[2]
Myocardial infarction	DIS655KI	Strong	Biomarker	[1]
Neurodevelopmental disorder with dysmorphic facies and variable seizures	DISW3CL3	Strong	Autosomal recessive	[5]
Global developmental delay with or without impaired intellectual development	DISAQVWQ	Limited	Autosomal recessive	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of ER membrane protein complex subunit 10 (EMC10).	[7]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ER membrane protein complex subunit 10 (EMC10).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ER membrane protein complex subunit 10 (EMC10).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of ER membrane protein complex subunit 10 (EMC10).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of ER membrane protein complex subunit 10 (EMC10).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of ER membrane protein complex subunit 10 (EMC10).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ER membrane protein complex subunit 10 (EMC10).	[13]

References

• [1] EMC10 (Endoplasmic Reticulum Membrane Protein Complex Subunit 10) Is a Bone Marrow-Derived Angiogenic Growth Factor Promoting Tissue Repair After Myocardial Infarction.Circulation. 2017 Nov 7;136(19):1809-1823. doi: 10.1161/CIRCULATIONAHA.117.029980. Epub 2017 Sep 20.
• [2] hHSS1: a novel secreted factor and suppressor of glioma growth located at chromosome 19q13.33.J Neurooncol. 2011 Apr;102(2):197-211. doi: 10.1007/s11060-010-0314-6. Epub 2010 Jul 31.
• [3] Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan, a new mouse model of band-3 deficiency.Blood. 2004 Apr 15;103(8):3233-40. doi: 10.1182/blood-2003-08-2813. Epub 2003 Dec 30.
• [4] EMC10 governs male fertility via maintaining sperm ion balance.J Mol Cell Biol. 2018 Dec 1;10(6):503-514. doi: 10.1093/jmcb/mjy024.
• [5] Whole Exome Sequencing of Patients from Multicase Families with Systemic Lupus Erythematosus Identifies Multiple Rare Variants. Sci Rep. 2018 Jun 8;8(1):8775. doi: 10.1038/s41598-018-26274-y.
• [6] EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay. Clin Genet. 2020 Dec;98(6):555-561. doi: 10.1111/cge.13842. Epub 2020 Sep 15.
• [7] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [8] 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.
• [9] 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.
• [10] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [11] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [12] 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.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.