Details of Drug Off-Target (DOT)

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

DOT Name ELKS/Rab6-interacting/CAST family member 1 (ERC1)
Synonyms ERC-1; Rab6-interacting protein 2
Gene Name ERC1
Related Disease
Acute myelogenous leukaemia ( )
Autism spectrum disorder ( )
Childhood apraxia of speech ( )
Complete hydatidiform mole ( )
Hepatitis C virus infection ( )
Thyroid gland papillary carcinoma ( )
Thyroid tumor ( )
Varicose veins ( )
Neoplasm ( )
Nervous system disease ( )
UniProt ID
RB6I2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF10174 ; PF09457
Sequence
MYGSARSVGKVEPSSQSPGRSPRLPRSPRLGHRRTNSTGGSSGSSVGGGSGKTLSMENIQ
SLNAAYATSGPMYLSDHENVGSETPKSTMTLGRSGGRLPYGVRMTAMGSSPNIASSGVAS
DTIAFGEHHLPPVSMASTVPHSLRQARDNTIMDLQTQLKEVLRENDLLRKDVEVKESKLS
SSMNSIKTFWSPELKKERALRKDEASKITIWKEQYRVVQEENQHMQMTIQALQDELRIQR
DLNQLFQQDSSSRTGEPCVAELTEENFQRLHAEHERQAKELFLLRKTLEEMELRIETQKQ
TLNARDESIKKLLEMLQSKGLSAKATEEDHERTRRLAEAEMHVHHLESLLEQKEKENSML
REEMHRRFENAPDSAKTKALQTVIEMKDSKISSMERGLRDLEEEIQMLKSNGALSTEERE
EEMKQMEVYRSHSKFMKNKVEQLKEELSSKEAQWEELKKKAAGLQAEIGQVKQELSRKDT
ELLALQTKLETLTNQFSDSKQHIEVLKESLTAKEQRAAILQTEVDALRLRLEEKETMLNK
KTKQIQDMAEEKGTQAGEIHDLKDMLDVKERKVNVLQKKIENLQEQLRDKEKQMSSLKER
VKSLQADTTNTDTALTTLEEALAEKERTIERLKEQRDRDEREKQEEIDNYKKDLKDLKEK
VSLLQGDLSEKEASLLDLKEHASSLASSGLKKDSRLKTLEIALEQKKEECLKMESQLKKA
HEAALEARASPEMSDRIQHLEREITRYKDESSKAQAEVDRLLEILKEVENEKNDKDKKIA
ELERQVKDQNKKVANLKHKEQVEKKKSAQMLEEARRREDNLNDSSQQLQDSLRKKDDRIE
ELEEALRESVQITAEREMVLAQEESARTNAEKQVEELLMAMEKVKQELESMKAKLSSTQQ
SLAEKETHLTNLRAERRKHLEEVLEMKQEALLAAISEKDANIALLELSSSKKKTQEEVAA
LKREKDRLVQQLKQQTQNRMKLMADNYEDDHFKSSHSNQTNHKPSPDQIIQPLLELDQNR
SKLKLYIGHLTTLCHDRDPLILRGLTPPASYNLDDDQAAWENELQKMTRGQLQDELEKGE
RDNAELQEFANAILQQIADHCPDILEQVVNALEESS
Function
Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex. May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport.
Tissue Specificity
Widely expressed. Isoform 2 and isoform 4 are abundantly expressed in brain. Isoform 1 and isoform 3 are predominantly expressed in testis and thyroid, and isoform 1 predominates in other tissues tested.
KEGG Pathway
NF-kappa B sig.ling pathway (hsa04064 )

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Strong Genetic Variation [1]
Autism spectrum disorder DISXK8NV Strong Biomarker [2]
Childhood apraxia of speech DISIR974 Strong Genetic Variation [3]
Complete hydatidiform mole DIS5QPI0 Strong Genetic Variation [4]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [5]
Thyroid gland papillary carcinoma DIS48YMM Strong Biomarker [6]
Thyroid tumor DISLVKMD Strong Biomarker [7]
Varicose veins DISIMBN2 Strong Biomarker [8]
Neoplasm DISZKGEW Limited Genetic Variation [6]
Nervous system disease DISJ7GGT Limited Genetic Variation [9]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 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 ELKS/Rab6-interacting/CAST family member 1 (ERC1). [10]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [13]
Decitabine DMQL8XJ Approved Decitabine affects the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [11]
Marinol DM70IK5 Approved Marinol increases the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [14]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [15]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [17]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [19]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [20]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [22]
geraniol DMS3CBD Investigative geraniol increases the expression of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [23]
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⏷ Show the Full List of 13 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [18]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of ELKS/Rab6-interacting/CAST family member 1 (ERC1). [21]
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References

1 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
2 A 1.5Mb terminal deletion of 12p associated with autism spectrum disorder.Gene. 2014 May 25;542(1):83-6. doi: 10.1016/j.gene.2014.02.058. Epub 2014 Mar 5.
3 12p13.33 microdeletion including ELKS/ERC1, a new locus associated with childhood apraxia of speech.Eur J Hum Genet. 2013 Jan;21(1):82-8. doi: 10.1038/ejhg.2012.116. Epub 2012 Jun 20.
4 Whole-exome sequencing reveals genetic variants in ERC1 and KCNG4 associated with complete hydatidiform mole in Chinese Han women.Oncotarget. 2017 Sep 8;8(43):75264-75271. doi: 10.18632/oncotarget.20769. eCollection 2017 Sep 26.
5 Hepatitis C virus NS3 protein interacts with ELKS-{delta} and ELKS-{alpha}, members of a novel protein family involved in intracellular transport and secretory pathways.J Gen Virol. 2005 Aug;86(Pt 8):2197-2208. doi: 10.1099/vir.0.80862-0.
6 Low prevalence of RET rearrangements (RET/PTC1, RET/PTC2, RET/PTC3, and ELKS-RET) in sporadic papillary thyroid carcinomas in Taiwan Chinese.Thyroid. 2005 Apr;15(4):326-35. doi: 10.1089/thy.2005.15.326.
7 Differential expression of multiple isoforms of the ELKS mRNAs involved in a papillary thyroid carcinoma.Genes Chromosomes Cancer. 2002 Sep;35(1):30-7. doi: 10.1002/gcc.10095.
8 Dopamine Secretion Is Mediated by Sparse Active Zone-like Release Sites.Cell. 2018 Feb 8;172(4):706-718.e15. doi: 10.1016/j.cell.2018.01.008. Epub 2018 Feb 1.
9 1.39 Mb inherited interstitial deletion in 12p13.33 associated with developmental delay.Eur J Med Genet. 2011 Mar-Apr;54(2):198-203. doi: 10.1016/j.ejmg.2010.11.010. Epub 2010 Dec 7.
10 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.
11 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
12 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.
13 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
14 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
15 Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
16 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
17 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.
18 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
19 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
20 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.
21 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.
22 Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
23 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.