Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1YMP65)

• DOT Name: Spectrin alpha chain, erythrocytic 1 (SPTA1)
• Synonyms: Erythroid alpha-spectrin
• Gene Name: SPTA1
• Related Disease:
  Glioblastoma multiforme
  Hereditary spherocytosis type 1
  Hereditary spherocytosis type 3
  Anemia
  Beta thalassemia
  Carcinoma
  Colorectal carcinoma
  Elliptocytosis 2
  Fanconi anemia complementation group A
  Hemolytic anemia
  Hereditary haemolytic anemia
  Invasive aspergillosis
  Obesity
  Pyropoikilocytosis, hereditary
  Small-cell lung cancer
  Hereditary elliptocytosis
  Hereditary spherocytosis
  Malaria
  Advanced cancer
  Lymphoma
  Sickle cell-hemoglobin c disease syndrome
  Sickle-cell anaemia
• UniProt ID: SPTA1_HUMAN
• PDB ID: 1OWA; 3LBX; 5J4O
• Pfam ID: PF08726 ; PF00018 ; PF00435
• Sequence:
  MEQFPKETVVESSGPKVLETAEEIQERRQEVLTRYQSFKERVAERGQKLEDSYHLQVFKR
  DADDLGKWIMEKVNILTDKSYEDPTNIQGKYQKHQSLEAEVQTKSRLMSELEKTREERFT
  MGHSAHEETKAHIEELRHLWDLLLELTLEKGDQLLRALKFQQYVQECADILEWIGDKEAI
  ATSVELGEDWERTEVLHKKFEDFQVELVAKEGRVVEVNQYANECAEENHPDLPLIQSKQN
  EVNAAWERLRGLALQRQKALSNAANLQRFKRDVTEAIQWIKEKEPVLTSEDYGKDLVASE
  GLFHSHKGLERNLAVMSDKVKELCAKAEKLTLSHPSDAPQIQEMKEDLVSSWEHIRALAT
  SRYEKLQATYWYHRFSSDFDELSGWMNEKTAAINADELPTDVAGGEVLLDRHQQHKHEID
  SYDDRFQSADETGQDLVNANHEASDEVREKMEILDNNWTALLELWDERHRQYEQCLDFHL
  FYRDSEQVDSWMSRQEAFLENEDLGNSLGSAEALLQKHEDFEEAFTAQEEKIITVDKTAT
  KLIGDDHYDSENIKAIRDGLLARRDALREKAATRRRLLKESLLLQKLYEDSDDLKNWINK
  KKKLADDEDYKDIQNLKSRVQKQQVFEKELAVNKTQLENIQKTGQEMIEGGHYASDNVTT
  RLSEVASLWEELLEATKQKGTQLHEANQQLQFENNAEDLQRWLEDVEWQVTSEDYGKGLA
  EVQNRLRKHGLLESAVAARQDQVDILTDLAAYFEEIGHPDSKDIRARQESLVCRFEALKE
  PLATRKKKLLDLLHLQLICRDTEDEEAWIQETEPSATSTYLGKDLIASKKLLNRHRVILE
  NIASHEPRIQEITERGNKMVEEGHFAAEDVASRVKSLNQNMESLRARAARRQNDLEANVQ
  FQQYLADLHEAETWIREKEPIVDNTNYGADEEAAGALLKKHEAFLLDLNSFGDSMKALRN
  QANACQQQQAAPVEGVAGEQRVMALYDFQARSPREVTMKKGDVLTLLSSINKDWWKVEAA
  DHQGIVPAVYVRRLAHDEFPMLPQRRREEPGNITQRQEQIENQYRSLLDRAEERRRRLLQ
  RYNEFLLAYEAGDMLEWIQEKKAENTGVELDDVWELQKKFDEFQKDLNTNEPRLRDINKV
  ADDLLFEGLLTPEGAQIRQELNSRWGSLQRLADEQRQLLGSAHAVEVFHREADDTKEQIE
  KKCQALSAADPGSDLFSVQALQRRHEGFERDLVPLGDKVTILGETAERLSESHPDATEDL
  QRQKMELNEAWEDLQGRTKDRKESLNEAQKFYLFLSKARDLQNWISSIGGMVSSQELAED
  LTGIEILLERHQEHRADMEAEAPTFQALEDFSAELIDSGHHASPEIEKKLQAVKLERDDL
  EKAWEKRKKILDQCLELQMFQGNCDQVESWMVARENSLRSDDKSSLDSLEALMKKRDDLD
  KAITAQEGKITDLEHFAESLIADEHYAKEEIATRLQRVLDRWKALKAQLIDERTKLGDYA
  NLKQFYRDLEELEEWISEMLPTACDESYKDATNIQRKYLKHQTFAHEVDGRSEQVHGVIN
  LGNSLIECSACDGNEEAMKEQLEQLKEHWDHLLERTNDKGKKLNEASRQQRFNTSIRDFE
  FWLSEAETLLAMKDQARDLASAGNLLKKHQLLEREMLAREDALKDLNTLAEDLLSSGTFN
  VDQIVKKKDNVNKRFLNVQELAAAHHEKLKEAYALFQFFQDLDDEESWIEEKLIRVSSQD
  YGRDLQGVQNLLKKHKRLEGELVAHEPAIQNVLDMAEKLKDKAAVGQEEIQLRLAQFVEH
  WEKLKELAKARGLKLEESLEYLQFMQNAEEEEAWINEKNALAVRGDCGDTLAATQSLLMK
  HEALENDFAVHETRVQNVCAQGEDILNKVLQEESQNKEISSKIEALNEKTPSLAKAIAAW
  KLQLEDDYAFQEFNWKADVVEAWIADKETSLKTNGNGADLGDFLTLLAKQDTLDASLQSF
  QQERLPEITDLKDKLISAQHNQSKAIEERYAALLKRWEQLLEASAVHRQKLLEKQLPLQK
  AEDLFVEFAHKASALNNWCEKMEENLSEPVHCVSLNEIRQLQKDHEDFLASLARAQADFK
  CLLELDQQIKALGVPSSPYTWLTVEVLERTWKHLSDIIEEREQELQKEEARQVKNFEMCQ
  EFEQNASTFLQWILETRAYFLDGSLLKETGTLESQLEANKRKQKEIQAMKRQLTKIVDLG
  DNLEDALILDIKYSTIGLAQQWDQLYQLGLRMQHNLEQQIQAKDIKGVSEETLKEFSTIY
  KHFDENLTGRLTHKEFRSCLRGLNYYLPMVEEDEHEPKFEKFLDAVDPGRKGYVSLEDYT
  AFLIDKESENIKSSDEIENAFQALAEGKSYITKEDMKQALTPEQVSFCATHMQQYMDPRG
  RSHLSGYDYVGFTNSYFGN
• 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

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Hereditary spherocytosis type 1	DIS34V1Z	Definitive	Biomarker	[2]
Hereditary spherocytosis type 3	DISN6K2V	Definitive	Autosomal recessive	[3]
Anemia	DISTVL0C	Strong	Genetic Variation	[4]
Beta thalassemia	DIS5RCQK	Strong	Genetic Variation	[5]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Elliptocytosis 2	DIS0V0LT	Strong	Autosomal dominant	[3]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Altered Expression	[8]
Hemolytic anemia	DIS803XQ	Strong	Genetic Variation	[9]
Hereditary haemolytic anemia	DIS487SI	Strong	Genetic Variation	[10]
Invasive aspergillosis	DISAI029	Strong	Biomarker	[11]
Obesity	DIS47Y1K	Strong	Biomarker	[12]
Pyropoikilocytosis, hereditary	DISZGN3B	Strong	Autosomal recessive	[13]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[14]
Hereditary elliptocytosis	DISA71F4	Supportive	Autosomal dominant	[15]
Hereditary spherocytosis	DISQYJP5	Supportive	Autosomal dominant	[15]
Malaria	DISQ9Y50	Disputed	Genetic Variation	[16]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[17]
Lymphoma	DISN6V4S	Limited	Biomarker	[18]
Sickle cell-hemoglobin c disease syndrome	DISX4EOQ	Limited	Biomarker	[19]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Spectrin alpha chain, erythrocytic 1 (SPTA1).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Spectrin alpha chain, erythrocytic 1 (SPTA1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Spectrin alpha chain, erythrocytic 1 (SPTA1).	[22]

References

• [1] Identifying Mutually Exclusive Gene Sets with Prognostic Value and Novel Potential Driver Genes in Patients with Glioblastoma.Biomed Res Int. 2019 Nov 5;2019:4860367. doi: 10.1155/2019/4860367. eCollection 2019.
• [2] Spectrin deficient inherited hemolytic anemias in the mouse: characterization by spectrin synthesis and mRNA activity in reticulocytes.Cell. 1984 Jul;37(3):721-9. doi: 10.1016/0092-8674(84)90408-2.
• [3] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [4] Three Novel Spectrin Variants in Jaundiced Neonates.Clin Pediatr (Phila). 2018 Jan;57(1):19-26. doi: 10.1177/0009922816687326. Epub 2017 Jan 15.
• [5] Analysis of erythrocyte and platelet membrane proteins in various forms of beta-thalassemia.Biochemistry (Mosc). 2004 Jul;69(7):748-53. doi: 10.1023/b:biry.0000040198.62939.56.
• [6] Loss of heterozygosity on chromosome 1q in human breast cancer.Proc Natl Acad Sci U S A. 1989 Sep;86(18):7204-7. doi: 10.1073/pnas.86.18.7204.
• [7] Phosphoproteome Characterization of Human Colorectal Cancer SW620 Cell-Derived Exosomes and New Phosphosite Discovery for C-HPP.J Proteome Res. 2016 Nov 4;15(11):4060-4072. doi: 10.1021/acs.jproteome.6b00391. Epub 2016 Aug 11.
• [8] Non-erythroid alpha spectrin prevents telomere dysfunction after DNA interstrand cross-link damage.Nucleic Acids Res. 2013 May 1;41(10):5321-40. doi: 10.1093/nar/gkt235. Epub 2013 Apr 9.
• [9] An insulator with barrier-element activity promotes alpha-spectrin gene expression in erythroid cells.Blood. 2009 Feb 12;113(7):1547-54. doi: 10.1182/blood-2008-06-164954. Epub 2008 Nov 13.
• [10] Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia.Int J Hematol. 2018 Sep;108(3):306-311. doi: 10.1007/s12185-018-2482-7. Epub 2018 Jun 23.
• [11] Molecular mechanism of Aspergillus fumigatus biofilm disruption by fungal and bacterial glycoside hydrolases.J Biol Chem. 2019 Jul 12;294(28):10760-10772. doi: 10.1074/jbc.RA119.008511. Epub 2019 Jun 5.
• [12] Chromosomal architecture and placental expression of the human growth hormone gene family are targeted by pre-pregnancy maternal obesity.Am J Physiol Endocrinol Metab. 2018 Oct 1;315(4):E435-E445. doi: 10.1152/ajpendo.00042.2018. Epub 2018 May 15.
• [13] A common type of the spectrin alpha I 46-50a-kD peptide abnormality in hereditary elliptocytosis and pyropoikilocytosis is associated with a mutation distant from the proteolytic cleavage site. Evidence for the functional importance of the triple helical model of spectrin. J Clin Invest. 1992 Mar;89(3):892-8. doi: 10.1172/JCI115669.
• [14] Expression and clinical significance of genes frequently mutated in small cell lung cancers defined by whole exome/RNA sequencing.Carcinogenesis. 2015 Jun;36(6):616-21. doi: 10.1093/carcin/bgv026. Epub 2015 Apr 11.
• [15] 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.
• [16] Spectrin-based skeleton in red blood cells and malaria.Curr Opin Hematol. 2007 May;14(3):198-202. doi: 10.1097/MOH.0b013e3280d21afd.
• [17] The Spanish biology/disease initiative within the human proteome project: Application to rheumatic diseases.J Proteomics. 2015 Sep 8;127(Pt B):406-13. doi: 10.1016/j.jprot.2015.01.023. Epub 2015 Feb 14.
• [18] Patterns of spectrin expression in B-cell lymphomas: loss of spectrin isoforms is associated with nodule-forming and germinal center-related lymphomas.Mod Pathol. 2007 Dec;20(12):1245-52. doi: 10.1038/modpathol.3800962. Epub 2007 Sep 21.
• [19] Increased cation permeability in mutant mouse red blood cells with defective membrane skeletons.Blood. 1995 Dec 1;86(11):4307-14.
• [20] MIP-1beta, a novel biomarker for in vitro sensitization test using human monocytic cell line. Toxicol In Vitro. 2006 Aug;20(5):736-42.
• [21] 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.
• [22] 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.