Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR5869N)

• DOT Name: Keratin-associated protein 10-3 (KRTAP10-3)
• Synonyms: High sulfur keratin-associated protein 10.3; Keratin-associated protein 10.3; Keratin-associated protein 18-3; Keratin-associated protein 18.3
• Gene Name: KRTAP10-3
• UniProt ID: KR103_HUMAN
• Pfam ID: PF13885
• Sequence:
  MATSTMSVCSSAYSDSWQVDACPESCCEPPCCATSCCAPAPCLTLVCTPVSCVSSPCCQA
  ACEPSPCQSGCTSSCTPSCCQQSSCQPACCTSSPCQQACCVPVCCKPVCCVPVCCKPVCC
  KPICCVPVCSGASSSCCQQSSRQPACCTTSCCRPSSSVSLLCRPVCRSTCCVPIPSCCAP
  ASTCQPSCCRPASCVSLLCRPTCSRLSSACCGLSSGQKSSC
• Function: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
• Tissue Specificity: Restricted to a narrow region of the hair fiber cuticle, lying approximately 20 cell layers above the apex of the dermal papilla of the hair root; not detected in any other tissues.
• Reactome Pathway: Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

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 Keratin-associated protein 10-3 (KRTAP10-3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Keratin-associated protein 10-3 (KRTAP10-3).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Keratin-associated protein 10-3 (KRTAP10-3).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Pantothenic acid	DM091H2	Approved	Pantothenic acid decreases the expression of Keratin-associated protein 10-3 (KRTAP10-3).	[2]

References

• [1] 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.
• [2] Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
• [3] 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.
• [4] 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.