Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKJND3Z)

• DOT Name: Protein 4.2 (EPB42)
• Synonyms: P4.2; Erythrocyte membrane protein band 4.2; Erythrocyte protein 4.2
• Gene Name: EPB42
• Related Disease:
  Hereditary spherocytosis type 1
  Hereditary elliptocytosis
  Hereditary spherocytosis type 5
  Hereditary spherocytosis
• UniProt ID: EPB42_HUMAN
• PDB ID: 7TVZ; 7TW0; 7TW1; 7TW3; 7TW5; 7TW6; 7UZS; 7V0K; 7V0Q; 8CS9; 8CSL; 8CSW; 8CTE
• Pfam ID: PF00927 ; PF01841 ; PF00868
• Sequence:
  MGQALGIKSCDFQAARNNEEHHTKALSSRRLFVRRGQPFTIILYFRAPVRAFLPALKKVA
  LTAQTGEQPSKINRTQATFPISSLGDRKWWSAVVEERDAQSWTISVTTPADAVIGHYSLL
  LQVSGRKQLLLGQFTLLFNPWNREDAVFLKNEAQRMEYLLNQNGLIYLGTADCIQAESWD
  FGQFEGDVIDLSLRLLSKDKQVEKWSQPVHVARVLGALLHFLKEQRVLPTPQTQATQEGA
  LLNKRRGSVPILRQWLTGRGRPVYDGQAWVLAAVACTVLRCLGIPARVVTTFASAQGTGG
  RLLIDEYYNEEGLQNGEGQRGRIWIFQTSTECWMTRPALPQGYDGWQILHPSAPNGGGVL
  GSCDLVPVRAVKEGTLGLTPAVSDLFAAINASCVVWKCCEDGTLELTDSNTKYVGNNIST
  KGVGSDRCEDITQNYKYPEGSLQEKEVLERVEKEKMEREKDNGIRPPSLETASPLYLLLK
  APSSLPLRGDAQISVTLVNHSEQEKAVQLAIGVQAVHYNGVLAAKLWRKKLHLTLSANLE
  KIITIGLFFSNFERNPPENTFLRLTAMATHSESNLSCFAQEDIAICRPHLAIKMPEKAEQ
  YQPLTASVSLQNSLDAPMEDCVISILGRGLIHRERSYRFRSVWPENTMCAKFQFTPTHVG
  LQRLTVEVDCNMFQNLTNYKSVTVVAPELSA
• Function: Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hereditary spherocytosis type 1	DIS34V1Z	Definitive	Biomarker	[1]
Hereditary elliptocytosis	DISA71F4	Strong	Biomarker	[2]
Hereditary spherocytosis type 5	DISNRKLV	Strong	Autosomal recessive	[3]
Hereditary spherocytosis	DISQYJP5	Supportive	Autosomal dominant	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Protein 4.2 (EPB42).	[5]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein 4.2 (EPB42).	[6]

References

• [1] Mild spherocytosis and altered red cell ion transport in protein 4. 2-null mice.J Clin Invest. 1999 Jun;103(11):1527-37. doi: 10.1172/JCI5766.
• [2] A point mutation in the protein 4.2 gene (allele 4.2 Tozeur) associated with hereditary haemolytic anaemia.Br J Haematol. 1995 Apr;89(4):762-70. doi: 10.1111/j.1365-2141.1995.tb08413.x.
• [3] Heavy transfusions and presence of an anti-protein 4.2 antibody in 4. 2(-) hereditary spherocytosis (949delG). Haematologica. 2000 Jan;85(1):19-24.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] 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.