Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8NJE5D)

DOT Name Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2)
Synonyms SIPA1-like protein 2
Gene Name SIPA1L2
Related Disease
Parkinson disease ( )
Schizophrenia ( )
Schwannoma ( )
Charcot-Marie-Tooth disease type 1A ( )
UniProt ID
SI1L2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00595 ; PF21022 ; PF02145 ; PF11881
Sequence
MSDPRQSQEEKHKLGRASSKFKDPPRIMQSDDYFARKFKAINGNMGPTTSLNASNSNETG
GGGPANGTPAVPKMGVRARVSEWPPKKDCSKELTCKALWESRSQTSYESITSVLQNGQSD
QSEGQQDEQLDLDFVEAKYTIGDIFVHSPQRGLHPIRQRSNSDVTISDIDAEDVLDQNAV
NPNTGAALHREYGSTSSIDRQGLSGENFFAMLRGYRVENYDHKAMVPFGFPEFFRCDPAI
SPSLHAAAQISRGEFVRISGLDYVDSALLMGRDRDKPFKRRLKSESVETSLFRKLRTVKS
EHETFKFTSELEESRLERGIRPWNCQRCFAHYDVQSILFNINEAMATRANVGKRKNITTG
ASAASQTQMPTGQTGNCESPLGSKEDLNSKENLDADEGDGKSNDLVLSCPYFRNETGGEG
DRRIALSRANSSSFSSGESCSFESSLSSHCTNAGVSVLEVPRENQPIHREKVKRYIIEHI
DLGAYYYRKFFYGKEHQNYFGIDENLGPVAVSIRREKVEDAKEKEGSQFNYRVAFRTSEL
TTLRGAILEDAIPSTARHGTARGLPLKEVLEYVIPELSIQCLRQASNSPKVSEQLLKLDE
QGLSFQHKIGILYCKAGQSTEEEMYNNETAGPAFEEFLDLLGQRVRLKGFSKYRAQLDNK
TDSTGTHSLYTTYKDYELMFHVSTLLPYMPNNRQQLLRKRHIGNDIVTIVFQEPGALPFT
PKSIRSHFQHVFVIVKVHNPCTENVCYSVGVSRSKDVPPFGPPIPKGVTFPKSAVFRDFL
LAKVINAENAAHKSEKFRAMATRTRQEYLKDLAENFVTTATVDTSVKFSFITLGAKKKEK
VKPRKDAHLFSIGAIMWHVIARDFGQSADIECLLGISNEFIMLIEKDSKNVVFNCSCRDV
IGWTSGLVSIKVFYERGECVLLSSVDNCAEDIREIVQRLVIVTRGCETVEMTLRRNGLGQ
LGFHVNFEGIVADVEPFGFAWKAGLRQGSRLVEICKVAVATLTHEQMIDLLRTSVTVKVV
IIQPHDDGSPRRGCSELCRIPMVEYKLDSEGTPCEYKTPFRRNTTWHRVPTPALQPLSRA
SPIPGTPDRLPCQQLLQQAQAAIPRSTSFDRKLPDGTRSSPSNQSSSSDPGPGGSGPWRP
QVGYDGCQSPLLLEHQGSGPLECDGAREREDTMEASRHPETKWHGPPSKVLGSYKERALQ
KDGSCKDSPNKLSHIGDKSCSSHSSSNTLSSNTSSNSDDKHFGSGDLMDPELLGLTYIKG
ASTDSGIDTAPCMPATILGPVHLAGSRSLIHSRAEQWADAADVSGPDDEPAKLYSVHGYA
STISAGSAAEGSMGDLSEISSHSSGSHHSGSPSAHCSKSSGSLDSSKVYIVSHSSGQQVP
GSMSKPYHRQGAVNKYVIGWKKSEGSPPPEEPEVTECPGMYSEMDVMSTATQHQTVVGDA
VAETQHVLSKEDFLKLMLPDSPLVEEGRRKFSFYGNLSPRRSLYRTLSDESICSNRRGSS
FGSSRSSVLDQALPNDILFSTTPPYHSTLPPRAHPAPSMGSLRNEFWFSDGSLSDKSKCA
DPGLMPLPDTATGLDWTHLVDAARAFEGLDSDEELGLLCHHTSYLDQRVASFCTLTDMQH
GQDLEGAQELPLCVDPGSGKEFMDTTGERSPSPLTGKVNQLELILRQLQTDLRKEKQDKA
VLQAEVQHLRQDNMRLQEESQTATAQLRKFTEWFFTTIDKKS
KEGG Pathway
Rap1 sig.ling pathway (hsa04015 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Parkinson disease DISQVHKL Strong Genetic Variation [1]
Schizophrenia DISSRV2N Strong Genetic Variation [2]
Schwannoma DISTTVLA Strong Biomarker [3]
Charcot-Marie-Tooth disease type 1A DISSRZG7 Limited Biomarker [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
24 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [4]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [5]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [6]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [7]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [8]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [10]
Testosterone DM7HUNW Approved Testosterone increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [10]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [11]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [8]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [12]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [13]
Ethinyl estradiol DMODJ40 Approved Ethinyl estradiol affects the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [14]
Cidofovir DMA13GD Approved Cidofovir decreases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [15]
Ifosfamide DMCT3I8 Approved Ifosfamide decreases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [15]
Clodronate DM9Y6X7 Approved Clodronate decreases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [15]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [16]
Genistein DM0JETC Phase 2/3 Genistein affects the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [17]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [18]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [19]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [20]
Mivebresib DMCPF90 Phase 1 Mivebresib increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [21]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [23]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [24]
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⏷ Show the Full List of 24 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Signal-induced proliferation-associated 1-like protein 2 (SIPA1L2). [22]
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References

1 Association analyses of variants of SIPA1L2, MIR4697, GCH1, VPS13C, and DDRGK1 with Parkinson's disease in East Asians.Neurobiol Aging. 2018 Aug;68:159.e7-159.e14. doi: 10.1016/j.neurobiolaging.2018.03.005. Epub 2018 Mar 10.
2 Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
3 Variation in SIPA1L2 is correlated with phenotype modification in Charcot- Marie- Tooth disease type 1A.Ann Neurol. 2019 Mar;85(3):316-330. doi: 10.1002/ana.25426.
4 Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
5 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
6 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
7 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
8 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.
9 Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
10 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
11 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
12 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
13 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
14 The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.
15 Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
16 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
17 Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
18 Gene expression profiling of A549 cells exposed to Milan PM2.5. Toxicol Lett. 2012 Mar 7;209(2):136-45.
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 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
21 Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
22 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.
23 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
24 In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.