Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNYFUM3)

DOT Name Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3)
Synonyms SIPA1-like protein 3; SPA-1-like protein 3
Gene Name SIPA1L3
Related Disease
Chronic renal failure ( )
Acute monocytic leukemia ( )
Acute myelogenous leukaemia ( )
Cataract ( )
Lung adenocarcinoma ( )
Total early-onset cataract ( )
Cataract 45 ( )
UniProt ID
SI1L3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00595 ; PF21022 ; PF02145 ; PF11881
Sequence
MTTYRAIPSDGVDLAASCGARVGDVLPGPHTGDYAPLGFWAQNGSMSQPLGESPATATAT
ATATTRPSPTTPAMPKMGVRARVADWPPKREALREHSNPSPSQDTDGTKATKMAHSMRSI
QNGQPPTSTPASSGSKAFHRLSRRRSKDVEFQDGWPRSPGRAFLPLRHRSSSEITLSECD
AEDAGEPRGARHTGALPLFREYGSTSSIDVQGMPEQSFFDILNEFRSEQPDARGCQALTE
LLRADPGPHLMGGGGGAKGDSHNGQPAKDSLLPLQPTKEKEKARKKPARGLGGGDTVDSS
IFRKLRSSKPEGEAGRSPGEADEGRSPPEASRPWVCQKSFAHFDVQSMLFDLNEAAANRV
SVSQRRNTTTGASAASAASAMASLTASRAHSLGGLDPAFTSTEDLNCKENLEQDLGDDNS
NDLLLSCPHFRNEIGGECERNVSFSRASVGSPSSGEGHLAEPALSAYRTNASISVLEVPK
EQQRTQSRPRQYSIEHVDLGARYYQDYFVGKEHANYFGVDEKLGPVAVSIKREKLEDHKE
HGPQYQYRIIFRTRELITLRGSILEDATPTATKHGTGRGLPLKDALEYVIPELNIHCLRL
ALNTPKVTEQLLKLDEQGLCRKHKVGILYCKAGQSSEEEMYNNEEAGPAFEEFLSLIGEK
VCLKGFTKYAAQLDVKTDSTGTHSLYTMYQDYEIMFHVSTLLPYTPNNRQQLLRKRHIGN
DIVTIIFQEPGALPFTPKNIRSHFQHVFIIVRVHNPCTDNVCYSMAVTRSKDAPPFGPPI
PSGTTFRKSDVFRDFLLAKVINAENAAHKSDKFHTMATRTRQEYLKDLAENCVSNTPIDS
TGKFNLISLTSKKKEKTKARAGAEQHSAGAIAWRVVAQDYAQGVEIDCILGISNEFVVLL
DLRTKEVVFNCYCGDVIGWTPDSSTLKIFYGRGDHIFLQATEGSVEDIREIVQRLKVMTS
GWETVDMTLRRNGLGQLGFHVKYDGTVAEVEDYGFAWQAGLRQGSRLVEICKVAVVTLTH
DQMIDLLRTSVTVKVVIIPPFEDGTPRRGWPETYDMNTSEPKTEQESITPGGRPPYRSNA
PWQWSGPASHNSLPASKWATPTTPGHAQSLSRPLKQTPIVPFRESQPLHSKRPVSFPETP
YTVSPAGADRVPPYRQPSGSFSTPGSATYVRYKPSPERYTAAPHPLLSLDPHFSHDGTSS
GDSSSGGLTSQESTMERQKPEPLWHVPAQARLSAIAGSSGNKHPSRQDAAGKDSPNRHSK
GEPQYSSHSSSNTLSSNASSSHSDDRWFDPLDPLEPEQDPLSKGGSSDSGIDTTLYTSSP
SCMSLAKAPRPAKPHKPPGSMGLCGGGREAAGRSHHADRRREVSPAPAVAGQSKGYRPKL
YSSGSSTPTGLAGGSRDPPRQPSDMGSRVGYPAQVYKTASAETPRPSQLAQPSPFQLSAS
VPKSFFSKQPVRNKHPTGWKRTEEPPPRPLPFSDPKKQVDTNTKNVFGQPRLRASLRDLR
SPRKNYKSTIEDDLKKLIIMDNLGPEQERDTGQSPQKGLQRTLSDESLCSGRREPSFASP
AGLEPGLPSDVLFTSTCAFPSSTLPARRQHQHPHPPVGPGATPAAGSGFPEKKSTISASE
LSLADGRDRPLRRLDPGLMPLPDTAAGLEWSSLVNAAKAYEVQRAVSLFSLNDPALSPDI
PPAHSPVHSHLSLERGPPTPRTTPTMSEEPPLDLTGKVYQLEVMLKQLHTDLQKEKQDKV
VLQSEVASLRQNNQRLQEESQAASEQLRKFAEIFCREKKEL
Function Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens.
KEGG Pathway
Rap1 sig.ling pathway (hsa04015 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Chronic renal failure DISGG7K6 Definitive Genetic Variation [1]
Acute monocytic leukemia DIS28NEL Strong Genetic Variation [2]
Acute myelogenous leukaemia DISCSPTN Strong Genetic Variation [2]
Cataract DISUD7SL Strong Posttranslational Modification [3]
Lung adenocarcinoma DISD51WR Strong Posttranslational Modification [4]
Total early-onset cataract DISACMEZ Supportive Autosomal dominant [5]
Cataract 45 DIS44GNP Limited Semidominant [6]
------------------------------------------------------------------------------------
⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 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 Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [7]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [17]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [18]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [19]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [18]
------------------------------------------------------------------------------------
⏷ Show the Full List of 6 Drug(s)
9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [9]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [10]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [11]
Marinol DM70IK5 Approved Marinol increases the expression of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [13]
Selenium DM25CGV Approved Selenium increases the expression of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [14]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [15]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [16]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Signal-induced proliferation-associated 1-like protein 3 (SIPA1L3). [14]
------------------------------------------------------------------------------------
⏷ Show the Full List of 9 Drug(s)

References

1 Identification of CDC42BPG as a novel susceptibility locus for hyperuricemia in a Japanese population.Mol Genet Genomics. 2018 Apr;293(2):371-379. doi: 10.1007/s00438-017-1394-1. Epub 2017 Nov 9.
2 Dissecting TSC2-mutated renal and hepatic angiomyolipomas in an individual with ARID1B-associated intellectual disability.BMC Cancer. 2019 May 10;19(1):435. doi: 10.1186/s12885-019-5633-1.
3 Screening of methylation genes in age-related cataract.Int J Ophthalmol. 2018 Jul 18;11(7):1102-1107. doi: 10.18240/ijo.2018.07.05. eCollection 2018.
4 SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival: an epigenomic-smoking interaction analysis.Mol Oncol. 2019 May;13(5):1235-1248. doi: 10.1002/1878-0261.12482. Epub 2019 Apr 17.
5 SIPA1L3 identified by linkage analysis and whole-exome sequencing as a novel gene for autosomal recessive congenital cataract. Eur J Hum Genet. 2015 Dec;23(12):1627-33. doi: 10.1038/ejhg.2015.46. Epub 2015 Mar 25.
6 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
7 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.
8 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.
9 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
10 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
11 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
12 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.
13 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.
14 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
15 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
16 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
17 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.
18 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.
19 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.