Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT33BHEP)

• DOT Name: Protein FAM171A1 (FAM171A1)
• Synonyms: Astroprincin; APCN
• Gene Name: FAM171A1
• Related Disease:
  Narcolepsy
  Triple negative breast cancer
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: F1711_HUMAN
• Pfam ID: PF20771 ; PF10577
• Sequence:
  MSRSATLLLCLLGCHVWKAVTKTLREPGAGAQEVTLKVHISDASTHQPVADALIEIFTNQ
  ASIASGTSGTDGVAFIKFQYKLGSQLIVTASKHAYVPNSAPWKPIRLPVFSSLSLGLLPE
  RSATLMVYEDVVQIVSGFQGARPQPRVHFQRRALRLPENTSYSDLTAFLTAASSPSEVDS
  FPYLRGLDGNGTGNSTRHDLTPVTAVSVHLLSSNGTPVLVDGPIYVTVPLATQSSLRHNA
  YVAAWRFDQKLGTWLKSGLGLVHQEGSQLTWTYIAPQLGYWVAAMSPPIPGPVVTQDITT
  YHTVFLLAILGGMAFILLVLLCLLLYYCRRKCLKPRQHHRKLQLPAGLESSKRDQSTSMS
  HINLLFSRRASEFPGPLSVTSHGRPEAPGTKELMSGVHLEMMSPGGEGDLHTPMLKLSYS
  TSQEFSSREELLSCKEEDKSQISFDNLTPSGTLGKDYHKSVEVFPLKARKSMEREGYESS
  GNDDYRGSYNTVLSQPLFEKQDREGPASTGSKLTIQEHLYPAPSSPEKEQLLDRRPTECM
  MSRSVDHLERPTSFPRPGQLICCSSVDQVNDSVYRKVLPALVIPAHYMKLPGDHSYVSQP
  LVVPADQQLEIERLQAELSNPHAGIFPHPSSQIQPQPLSSQAISQQHLQDAGTREWSPQN
  ASMSESLSIPASLNDAALAQMNSEVQLLTEKALMELGGGKPLPHPRAWFVSLDGRSNAHV
  RHSYIDLQRAGRNGSNDASLDSGVDMNEPKSARKGRGDALSLQQNYPPVQEHQQKEPRAP
  DSTAYTQLVYLDDVEQSGSECGTTVCTPEDSALRCLLEGSSRRSGGQLPSLQEETTRRTA
  DAPSEPAASPHQRRSAHEEEEDDDDDDQGEDKKSPWQKREERPLMAFNIK
• Function: Involved in the regulation of the cytoskeletal dynamics, plays a role in actin stress fiber formation.
• Tissue Specificity: Expressed in heart, brain, liver, skeletal muscle, kidney and pancreas . In brain, expressed by glia, pyramidal neurons and astrocytes (at protein level) . Highly expressed in placental trophoblasts .

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[1]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	moderate	Biomarker	[2]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Protein FAM171A1 (FAM171A1) affects the response to substance of Doxorubicin.	[16]
Methotrexate	DM2TEOL	Approved	Protein FAM171A1 (FAM171A1) affects the response to substance of Methotrexate.	[16]
Fluorouracil	DMUM7HZ	Approved	Protein FAM171A1 (FAM171A1) affects the response to substance of Fluorouracil.	[16]
Etoposide	DMNH3PG	Approved	Protein FAM171A1 (FAM171A1) affects the response to substance of Etoposide.	[16]
Mitomycin	DMH0ZJE	Approved	Protein FAM171A1 (FAM171A1) affects the response to substance of Mitomycin.	[16]
Topotecan	DMP6G8T	Approved	Protein FAM171A1 (FAM171A1) affects the response to substance of Topotecan.	[16]

3 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 Protein FAM171A1 (FAM171A1).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein FAM171A1 (FAM171A1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein FAM171A1 (FAM171A1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein FAM171A1 (FAM171A1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein FAM171A1 (FAM171A1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein FAM171A1 (FAM171A1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein FAM171A1 (FAM171A1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein FAM171A1 (FAM171A1).	[9]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Protein FAM171A1 (FAM171A1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein FAM171A1 (FAM171A1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Protein FAM171A1 (FAM171A1).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein FAM171A1 (FAM171A1).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein FAM171A1 (FAM171A1).	[14]

References

• [1] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [2] Estrogen receptor- regulation of microRNA-590 targets FAM171A1-a modifier of breast cancer invasiveness.Oncogenesis. 2019 Jan 9;8(1):5. doi: 10.1038/s41389-018-0113-z.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] 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.
• [10] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [13] 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.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] 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.
• [16] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.