Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT78TJID)

• DOT Name: AKT-interacting protein (AKTIP)
• Synonyms: Ft1; Fused toes protein homolog
• Gene Name: AKTIP
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Hepatocellular carcinoma
  Non-insulin dependent diabetes
• UniProt ID: AKTIP_HUMAN
• Pfam ID: PF00179
• Sequence:
  MNPFWSMSTSSVRKRSEGEEKTLTGDVKTSPPRTAPKKQLPSIPKNALPITKPTSPAPAA
  QSTNGTHASYGPFYLEYSLLAEFTLVVKQKLPGVYVQPSYRSALMWFGVIFIRHGLYQDG
  VFKFTVYIPDNYPDGDCPRLVFDIPVFHPLVDPTSGELDVKRAFAKWRRNHNHIWQVLMY
  ARRVFYKIDTASPLNPEAAVLYEKDIQLFKSKVVDSVKVCTARLFDQPKIEDPYAISFSP
  WNPSVHDEAREKMLTQKKPEEQHNKSVHVAGLSWVKPGSVQPFSKEEKTVAT
• Function: Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). Regulates apoptosis by enhancing phosphorylation and activation of AKT1. Increases release of TNFSF6 via the AKT1/GSK3B/NFATC1 signaling cascade. FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[1]
Cervical carcinoma	DIST4S00	Strong	Genetic Variation	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]

8 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 AKT-interacting protein (AKTIP).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of AKT-interacting protein (AKTIP).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of AKT-interacting protein (AKTIP).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of AKT-interacting protein (AKTIP).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of AKT-interacting protein (AKTIP).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of AKT-interacting protein (AKTIP).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of AKT-interacting protein (AKTIP).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of AKT-interacting protein (AKTIP).	[13]

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 decreases the methylation of AKT-interacting protein (AKTIP).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of AKT-interacting protein (AKTIP).	[12]

References

• [1] Association of the miR-17-5p variants with susceptibility to cervical cancer in a Chinese population.Oncotarget. 2016 Nov 22;7(47):76647-76655. doi: 10.18632/oncotarget.12299.
• [2] The basal body gene, RPGRIP1L, is a candidate tumour suppressor gene in human hepatocellular carcinoma.Eur J Cancer. 2009 Jul;45(11):2041-9. doi: 10.1016/j.ejca.2009.04.012. Epub 2009 May 4.
• [3] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [4] 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.
• [5] 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.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.
• [12] 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.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.