Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1Q9ABM)

• DOT Name: Spectrin beta chain, erythrocytic (SPTB)
• Synonyms: Beta-I spectrin
• Gene Name: SPTB
• Related Disease:
  Cholangiocarcinoma
  Elliptocytosis 3
  Hemolytic anemia
  Hepatocellular carcinoma
  Hereditary spherocytosis type 1
  Hereditary spherocytosis type 2
  Myopathy
  Neoplasm
  Non-small-cell lung cancer
  Neonatal anemia
  Pyropoikilocytosis, hereditary
  Hereditary elliptocytosis
  Hereditary spherocytosis
• UniProt ID: SPTB1_HUMAN
• PDB ID: 1S35; 3EDU; 3F57; 3KBT; 3KBU; 3LBX
• Pfam ID: PF00307 ; PF00435
• Sequence:
  MTSATEFENVGNQPPYSRINARWDAPDDELDNDNSSARLFERSRIKALADEREVVQKKTF
  TKWVNSHLARVSCRITDLYKDLRDGRMLIKLLEVLSGEMLPKPTKGKMRIHCLENVDKAL
  QFLKEQRVHLENMGSHDIVDGNHRLVLGLIWTIILRFQIQDIVVQTQEGRETRSAKDALL
  LWCQMKTAGYPHVNVTNFTSSWKDGLAFNALIHKHRPDLIDFDKLKDSNARHNLEHAFNV
  AERQLGIIPLLDPEDVFTENPDEKSIITYVVAFYHYFSKMKVLAVEGKRVGKVIDHAIET
  EKMIEKYSGLASDLLTWIEQTITVLNSRKFANSLTGVQQQLQAFSTYRTVEKPPKFQEKG
  NLEVLLFTIQSRMRANNQKVYTPHDGKLVSDINRAWESLEEAEYRRELALRNELIRQEKL
  EQLARRFDRKAAMRETWLSENQRLVAQDNFGYDLAAVEAAKKKHEAIETDTAAYEERVRA
  LEDLAQELEKENYHDQKRITARKDNILRLWSYLQELLQSRRQRLETTLALQKLFQDMLHS
  IDWMDEIKAHLLSAEFGKHLLEVEDLLQKHKLMEADIAIQGDKVKAITAATLKFTEGKGY
  QPCDPQVIQDRISHLEQCFEELSNMAAGRKAQLEQSKRLWKFFWEMDEAESWIKEKEQIY
  SSLDYGKDLTSVLILQRKHKAFEDELRGLDAHLEQIFQEAHGMVARKQFGHPQIEARIKE
  VSAQWDQLKDLAAFCKKNLQDAENFFQFQGDADDLKAWLQDAHRLLSGEDVGQDEGATRA
  LGKKHKDFLEELEESRGVMEHLEQQAQGFPEEFRDSPDVTHRLQALRELYQQVVAQADLR
  QQRLQEALDLYTVFGETDACELWMGEKEKWLAEMEMPDTLEDLEVVQHRFDILDQEMKTL
  MTQIDGVNLAANSLVESGHPRSREVKQYQDHLNTRWQAFQTLVSERREAVDSALRVHNYC
  VDCEETSKWITDKTKVVESTKDLGRDLAGIIAIQRKLSGLERDVAAIQARVDALERESQQ
  LMDSHPEQKEDIGQRQKHLEELWQGLQQSLQGQEDLLGEVSQLQAFLQDLDDFQAWLSIT
  QKAVASEDMPESLPEAEQLLQQHAGIKDEIDGHQDSYQRVKESGEKVIQGQTDPEYLLLG
  QRLEGLDTGWNALGRMWESRSHTLAQCLGFQEFQKDAKQAEAILSNQEYTLAHLEPPDSL
  EAAEAGIRKFEDFLGSMENNRDKVLSPVDSGNKLVAEGNLYSDKIKEKVQLIEDRHRKNN
  EKAQEASVLLRDNLELQNFLQNCQELTLWINDKLLTSQDVSYDEARNLHNKWLKHQAFVA
  ELASHEGWLENIDAEGKQLMDEKPQFTALVSQKLEALHRLWDELQATTKEKTQHLSAARS
  SDLRLQTHADLNKWISAMEDQLRSDDPGKDLTSVNRMLAKLKRVEDQVNVRKEELGELFA
  QVPSMGEEGGDADLSIEKRFLDLLEPLGRRKKQLESSRAKLQISRDLEDETLWVEERLPL
  AQSADYGTNLQTVQLFMKKNQTLQNEILGHTPRVEDVLQRGQQLVEAAEIDCQDLEERLG
  HLQSSWDRLREAAAGRLQRLRDANEAQQYYLDADEAEAWIGEQELYVISDEIPKDEEGAI
  VMLKRHLRQQRAVEDYGRNIKQLASRAQGLLSAGHPEGEQIIRLQGQVDKHYAGLKDVAE
  ERKRKLENMYHLFQLKRETDDLEQWISEKELVASSPEMGQDFDHVTLLRDKFRDFARETG
  AIGQERVDNVNAFIERLIDAGHSEAATIAEWKDGLNEMWADLLELIDTRMQLLAASYDLH
  RYFYTGAEILGLIDEKHRELPEDVGLDASTAESFHRVHTAFERELHLLGVQVQQFQDVAT
  RLQTAYAGEKAEAIQNKEQEVSAAWQALLDACAGRRTQLVDTADKFRFFSMARDLLSWME
  SIIRQIETQERPRDVSSVELLMKYHQGINAEIETRSKNFSACLELGESLLQRQHQASEEI
  REKLQQVMSRRKEMNEKWEARWERLRMLLEVCQFSRDASVAEAWLIAQEPYLASGDFGHT
  VDSVEKLIKRHEAFEKSTASWAERFAALEKPTTLELKERQIAERPAEETGPQEEEGETAG
  EAPVSHHAATERTSPVSLWSRLSSSWESLQPEPSHPY
• Function: Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane. It associates with band 4.1 and actin to form the cytoskeletal superstructure of the erythrocyte plasma membrane.
• Reactome Pathway:
  Interaction between L1 and Ankyrins (R-HSA-445095)
  RAF/MAP kinase cascade (R-HSA-5673001)
  COPI-mediated anterograde transport (R-HSA-6807878)
  NCAM signaling for neurite out-growth (R-HSA-375165)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[1]
Elliptocytosis 3	DISSM670	Strong	Autosomal recessive	[2]
Hemolytic anemia	DIS803XQ	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Hereditary spherocytosis type 1	DIS34V1Z	Strong	Genetic Variation	[4]
Hereditary spherocytosis type 2	DISCYPC8	Strong	Autosomal dominant	[4]
Myopathy	DISOWG27	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Neonatal anemia	DISPFC78	moderate	Biomarker	[3]
Pyropoikilocytosis, hereditary	DISZGN3B	moderate	Genetic Variation	[4]
Hereditary elliptocytosis	DISA71F4	Supportive	Autosomal dominant	[7]
Hereditary spherocytosis	DISQYJP5	Supportive	Autosomal dominant	[7]

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 Spectrin beta chain, erythrocytic (SPTB).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Spectrin beta chain, erythrocytic (SPTB).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Spectrin beta chain, erythrocytic (SPTB).	[19]

10 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 Spectrin beta chain, erythrocytic (SPTB).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Spectrin beta chain, erythrocytic (SPTB).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Spectrin beta chain, erythrocytic (SPTB).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Spectrin beta chain, erythrocytic (SPTB).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Spectrin beta chain, erythrocytic (SPTB).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Spectrin beta chain, erythrocytic (SPTB).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Spectrin beta chain, erythrocytic (SPTB).	[16]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Spectrin beta chain, erythrocytic (SPTB).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Spectrin beta chain, erythrocytic (SPTB).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Spectrin beta chain, erythrocytic (SPTB).	[20]

References

• [1] Utilization of spectrins I and III in diagnosis of hepatocellular carcinoma.Ann Diagn Pathol. 2019 Apr;39:86-91. doi: 10.1016/j.anndiagpath.2019.02.009. Epub 2019 Feb 15.
• [2] An insertional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin nice (beta 220/216). Blood. 1991 Jul 15;78(2):517-23.
• [3] Mutation of a highly conserved residue of betaI spectrin associated with fatal and near-fatal neonatal hemolytic anemia.J Clin Invest. 1997 Jan 15;99(2):267-77. doi: 10.1172/JCI119155.
• [4] Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis. Clin Genet. 2016 Jul;90(1):69-78. doi: 10.1111/cge.12749. Epub 2016 Mar 15.
• [5] The lethal hemolytic mutation in beta I sigma 2 spectrin Providence yields a null phenotype in neonatal skeletal muscle.Lab Invest. 1996 Jun;74(6):1117-29.
• [6] 4.1N is involved in a flotillin-1/-catenin/Wnt pathway and suppresses cell proliferation and migration in non-small cell lung cancer cell lines.Tumour Biol. 2016 Sep;37(9):12713-12723. doi: 10.1007/s13277-016-5146-3. Epub 2016 Jul 22.
• [7] Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. Blood Rev. 2013 Jul;27(4):167-78. doi: 10.1016/j.blre.2013.04.003. Epub 2013 May 9.
• [8] 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.
• [9] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] 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.
• [13] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] 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.
• [16] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [17] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [18] 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.
• [19] 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.
• [20] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.