Details of Drug Off-Target (DOT)

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

• DOT Name: Keratin, type I cuticular Ha2 (KRT32)
• Synonyms: Hair keratin, type I Ha2; Keratin-32; K32
• Gene Name: KRT32
• Related Disease:
  Clear cell renal carcinoma
  Influenza
  Papillary renal cell carcinoma
  Renal cell carcinoma
• UniProt ID: K1H2_HUMAN
• Pfam ID: PF00038
• Sequence:
  MTSSCCVTNNLQASLKSCPRPASVCSSGVNCRPELCLGYVCQPMACLPSVCLPTTFRPAS
  CLSKTYLSSSCQAASGISGSMGPGSWYSEGAFNGNEKETMQFLNDRLASYLTRVRQLEQE
  NAELESRIQEASHSQVLTMTPDYQSHFRTIEELQQKILCTKAENARMVVNIDNAKLAADD
  FRAKYEAELAMRQLVEADINGLRRILDDLTLCKADLEAQVESLKEELMCLKKNHEEEVGS
  LRCQLGDRLNIEVDAAPPVDLTRVLEEMRCQYEAMVEANRRDVEEWFNMQMEELNQQVAT
  SSEQLQNYQSDIIDLRRTVNTLEIELQAQHSLRDSLENTLTESEARYSSQLAQMQCMITN
  VEAQLAEIRADLERQNQEYQVLLDVRARLEGEINTYRSLLENEDCKLPCNPCSTPSCTTC
  VPSPCVPRTVCVPRTVGMPCSPCPQGRY
• Tissue Specificity: Restricted to the hair cuticle.
• KEGG Pathway:
  Estrogen sig.ling pathway (hsa04915)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[1]
Influenza	DIS3PNU3	Strong	Biomarker	[2]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[1]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[1]

2 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 Keratin, type I cuticular Ha2 (KRT32).	[3]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Keratin, type I cuticular Ha2 (KRT32).	[4]

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 Keratin, type I cuticular Ha2 (KRT32).	[5]

References

• [1] Integrated molecular analysis of clear-cell renal cell carcinoma.Nat Genet. 2013 Aug;45(8):860-7. doi: 10.1038/ng.2699. Epub 2013 Jun 24.
• [2] Insights into structural and inhibitory mechanisms of low pH-induced conformational change of influenza HA2 protein: a computational approach.J Mol Model. 2019 Mar 23;25(4):99. doi: 10.1007/s00894-019-3982-y.
• [3] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [4] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [5] 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.