Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6NMCK5)

DOT Name Trafficking protein particle complex subunit 12 (TRAPPC12)
Synonyms Tetratricopeptide repeat protein 15; TPR repeat protein 15; TTC-15; Trafficking of membranes and mitosis
Gene Name TRAPPC12
Related Disease
Aural atresia, congenital ( )
Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome ( )
UniProt ID
TPC12_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF14559 ; PF13174
Sequence
MEDAGGGEETPAPEAPHPPQLAPPEEQGLLFQEETIDLGGDEFGSEENETASEGSSPLAD
KLNEHMMESVLISDSPNSEGDAGDLGRVRDEAEPGGEGDPGPEPAGTPSPSGEADGDCAP
EDAAPSSGGAPRQDAAREVPGSEAARPEQEPPVAEPVPVCTIFSQRAPPASGDGFEPQMV
KSPSFGGASEASARTPPQVVQPSPSLSTFFGDTAASHSLASDFFDSFTTSAFISVSNPGA
GSPAPASPPPLAVPGTEGRPEPVAMRGPQAAAPPASPEPFAHIQAVFAGSDDPFATALSM
SEMDRRNDAWLPGEATRGVLRAVATQQRGAVFVDKENLTMPGLRFDNIQGDAVKDLMLRF
LGEKAAAKRQVLNADSVEQSFVGLKQLISCRNWRAAVDLCGRLLTAHGQGYGKSGLLTSH
TTDSLQLWFVRLALLVKLGLFQNAEMEFEPFGNLDQPDLYYEYYPHVYPGRRGSMVPFSM
RILHAELQQYLGNPQESLDRLHKVKTVCSKILANLEQGLAEDGGMSSVTQEGRQASIRLW
RSRLGRVMYSMANCLLLMKDYVLAVEAYHSVIKYYPEQEPQLLSGIGRISLQIGDIKTAE
KYFQDVEKVTQKLDGLQGKIMVLMNSAFLHLGQNNFAEAHRFFTEILRMDPRNAVANNNA
AVCLLYLGKLKDSLRQLEAMVQQDPRHYLHESVLFNLTTMYELESSRSMQKKQALLEAVA
GKEGDSFNTQCLKLA
Function
Component of the TRAPP complex, which is involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage. Also plays a role in chromosome congression, kinetochore assembly and stability and controls the recruitment of CENPE to the kinetochores.
Reactome Pathway
RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Aural atresia, congenital DISCP7UV Strong Genetic Variation [1]
Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome DISFBBYJ Strong Autosomal recessive [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Trafficking protein particle complex subunit 12 (TRAPPC12). [3]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Trafficking protein particle complex subunit 12 (TRAPPC12). [8]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Trafficking protein particle complex subunit 12 (TRAPPC12). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Trafficking protein particle complex subunit 12 (TRAPPC12). [10]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Trafficking protein particle complex subunit 12 (TRAPPC12). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Trafficking protein particle complex subunit 12 (TRAPPC12). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate affects the expression of Trafficking protein particle complex subunit 12 (TRAPPC12). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Trafficking protein particle complex subunit 12 (TRAPPC12). [7]
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References

1 Genome-wide pleiotropy analysis of neuropathological traits related to Alzheimer's disease.Alzheimers Res Ther. 2018 Feb 20;10(1):22. doi: 10.1186/s13195-018-0349-z.
2 Mutations in TRAPPC12 Manifest in Progressive Childhood Encephalopathy and Golgi Dysfunction. Am J Hum Genet. 2017 Aug 3;101(2):291-299. doi: 10.1016/j.ajhg.2017.07.006.
3 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.
4 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
9 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.
10 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.