General Information of Drug Off-Target (DOT) (ID: OTKDOC2M)

DOT Name Engulfment and cell motility protein 2 (ELMO2)
Synonyms Protein ced-12 homolog A; hCed-12A
Gene Name ELMO2
Related Disease
Primary intraosseous venous malformation ( )
Vascular malformation ( )
Ramon syndrome ( )
Adult glioblastoma ( )
Glioblastoma multiforme ( )
UniProt ID
ELMO2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6IDX; 6IE1
Pfam ID
PF11841 ; PF04727 ; PF16457
Sequence
MPPPSDIVKVAIEWPGANAQLLEIDQKRPLASIIKEVCDGWSLPNPEYYTLRYADGPQLY
ITEQTRSDIKNGTILQLAISPSRAARQLMERTQSSNMETRLDAMKELAKLSADVTFATEF
INMDGIIVLTRLVESGTKLLSHYSEMLAFTLTAFLELMDHGIVSWDMVSITFIKQIAGYV
SQPMVDVSILQRSLAILESMVLNSQSLYQKIAEEITVGQLISHLQVSNQEIQTYAIALIN
ALFLKAPEDKRQDMANAFAQKHLRSIILNHVIRGNRPIKTEMAHQLYVLQVLTFNLLEER
MMTKMDPNDQAQRDIIFELRRIAFDAESDPSNAPGSGTEKRKAMYTKDYKMLGFTNHINP
AMDFTQTPPGMLALDNMLYLAKVHQDTYIRIVLENSSREDKHECPFGRSAIELTKMLCEI
LQVGELPNEGRNDYHPMFFTHDRAFEELFGICIQLLNKTWKEMRATAEDFNKVMQVVREQ
ITRALPSKPNSLDQFKSKLRSLSYSEILRLRQSERMSQDDFQSPPIVELREKIQPEILEL
IKQQRLNRLCEGSSFRKIGNRRRQERFWYCRLALNHKVLHYGDLDDNPQGEVTFESLQEK
IPVADIKAIVTGKDCPHMKEKSALKQNKEVLELAFSILYDPDETLNFIAPNKYEYCIWID
GLSALLGKDMSSELTKSDLDTLLSMEMKLRLLDLENIQIPEAPPPIPKEPSSYDFVYHYG
Function
Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1.
Tissue Specificity Widely expressed, with a higher expression in skeletal muscle, kidney and placenta.
KEGG Pathway
Bacterial invasion of epithelial cells (hsa05100 )
Shigellosis (hsa05131 )
Salmonella infection (hsa05132 )
Yersinia infection (hsa05135 )
Reactome Pathway
VEGFA-VEGFR2 Pathway (R-HSA-4420097 )
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases (R-HSA-8849471 )
RHOG GTPase cycle (R-HSA-9013408 )
FCGR3A-mediated phagocytosis (R-HSA-9664422 )
Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Primary intraosseous venous malformation DISSM0B0 Strong Autosomal recessive [1]
Vascular malformation DIS2DB7A Strong Genetic Variation [2]
Ramon syndrome DISCTV2L Supportive Autosomal recessive [3]
Adult glioblastoma DISVP4LU Limited Biomarker [4]
Glioblastoma multiforme DISK8246 Limited Biomarker [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Engulfment and cell motility protein 2 (ELMO2). [5]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Engulfment and cell motility protein 2 (ELMO2). [6]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Engulfment and cell motility protein 2 (ELMO2). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Engulfment and cell motility protein 2 (ELMO2). [8]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Engulfment and cell motility protein 2 (ELMO2). [9]
Testosterone DM7HUNW Approved Testosterone increases the expression of Engulfment and cell motility protein 2 (ELMO2). [9]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Engulfment and cell motility protein 2 (ELMO2). [10]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Engulfment and cell motility protein 2 (ELMO2). [11]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Engulfment and cell motility protein 2 (ELMO2). [12]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Engulfment and cell motility protein 2 (ELMO2). [13]
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⏷ Show the Full List of 9 Drug(s)

References

1 Loss-of-Function Mutations in ELMO2 Cause Intraosseous Vascular Malformation by Impeding RAC1 Signaling. Am J Hum Genet. 2016 Aug 4;99(2):299-317. doi: 10.1016/j.ajhg.2016.06.008. Epub 2016 Jul 28.
2 Clinical and Molecular Study of ELMO-2-Related Massive Intraosseous Vascular Malformations: Lessons Learned From 25 Years of Follow-up.Ann Plast Surg. 2019 Sep;83(3):293-299. doi: 10.1097/SAP.0000000000001786.
3 Homozygous mutation in ELMO2 may cause Ramon syndrome. Clin Genet. 2018 Mar;93(3):703-706. doi: 10.1111/cge.13166. Epub 2018 Jan 25.
4 HGF-induced formation of the MET-AXL-ELMO2-DOCK180 complex promotes RAC1 activation, receptor clustering, and cancer cell migration and invasion.J Biol Chem. 2018 Oct 5;293(40):15397-15418. doi: 10.1074/jbc.RA118.003063. Epub 2018 Aug 14.
5 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
6 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
7 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
8 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.
9 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
10 Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on cervical carcinoma cells. Int J Gynecol Cancer. 2006 May-Jun;16(3):1321-9.
11 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
12 Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
13 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.