Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHI37BJ)

• DOT Name: Protein-glutamine gamma-glutamyltransferase 5 (TGM5)
• Synonyms: EC 2.3.2.13; Transglutaminase X; TG(X); TGX; TGase X; Transglutaminase-5; TGase-5
• Gene Name: TGM5
• Related Disease: Acral peeling skin syndrome
• UniProt ID: TGM5_HUMAN
• EC Number: 2.3.2.13
• Pfam ID: PF00927 ; PF01841 ; PF00868
• Sequence:
  MAQGLEVALTDLQSSRNNVRHHTEEITVDHLLVRRGQAFNLTLYFRNRSFQPGLDNIIFV
  VETGPLPDLALGTRAVFSLARHHSPSPWIAWLETNGATSTEVSLCAPPTAAVGRYLLKIH
  IDSFQGSVTAYQLGEFILLFNPWCPEDAVYLDSEPQRQEYVMNDYGFIYQGSKNWIRPCP
  WNYGQFEDKIIDICLKLLDKSLHFQTDPATDCALRGSPVYVSRVVCAMINSNDDNGVLNG
  NWSENYTDGANPAEWTGSVAILKQWNATGCQPVRYGQCWVFAAVMCTVMRCLGIPTRVIT
  NFDSGHDTDGNLIIDEYYDNTGRILGNKKKDTIWNFHVWNECWMARKDLPPAYGGWQVLD
  ATPQEMSNGVYCCGPASVRAIKEGEVDLNYDTPFVFSMVNADCMSWLVQGGKEQKLHQDT
  SSVGNFISTKSIQSDERDDITENYKYEEGSLQERQVFLKALQKLKARSFHGSQRGAELQP
  SRPTSLSQDSPRSLHTPSLRPSDVVQVSLKFKLLDPPNMGQDICFVLLALNMSSQFKDLK
  VNLSAQSLLHDGSPLSPFWQDTAFITLSPKEAKTYPCKISYSQYSQYLSTDKLIRISALG
  EEKSSPEKILVNKIITLSYPSITINVLGAAVVNQPLSIQVIFSNPLSEQVEDCVLTVEGS
  GLFKKQQKVFLGVLKPQHQASIILETVPFKSGQRQIQANMRSNKFKDIKGYRNVYVDFAL
• Function: Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Contributes to the formation of the cornified cell envelope of keratinocytes.
• Tissue Specificity: Expressed in foreskin keratinocytes.
• Reactome Pathway: Formation of the cornified envelope (R-HSA-6809371)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acral peeling skin syndrome	DIS7NJUZ	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein-glutamine gamma-glutamyltransferase 5 (TGM5).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein-glutamine gamma-glutamyltransferase 5 (TGM5).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein-glutamine gamma-glutamyltransferase 5 (TGM5).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein-glutamine gamma-glutamyltransferase 5 (TGM5).	[5]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Protein-glutamine gamma-glutamyltransferase 5 (TGM5).	[6]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Protein-glutamine gamma-glutamyltransferase 5 (TGM5).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein-glutamine gamma-glutamyltransferase 5 (TGM5).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein-glutamine gamma-glutamyltransferase 5 (TGM5).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein-glutamine gamma-glutamyltransferase 5 (TGM5).	[9]

References

• [1] 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.
• [2] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Differentiation-specific factors modulate epidermal CYP1-4 gene expression in human skin in response to retinoic acid and classic aryl hydrocarbon receptor ligands. J Pharmacol Exp Ther. 2006 Dec;319(3):1162-71.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.