Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOGFMI6)

• DOT Name: PMS1 protein homolog 1 (PMS1)
• Synonyms: DNA mismatch repair protein PMS1
• Gene Name: PMS1
• Related Disease: Lynch syndrome
• UniProt ID: PMS1_HUMAN
• PDB ID: 2CS1
• Pfam ID: PF01119 ; PF13589 ; PF00505
• Sequence:
  MKQLPAATVRLLSSSQIITSVVSVVKELIENSLDAGATSVDVKLENYGFDKIEVRDNGEG
  IKAVDAPVMAMKYYTSKINSHEDLENLTTYGFRGEALGSICCIAEVLITTRTAADNFSTQ
  YVLDGSGHILSQKPSHLGQGTTVTALRLFKNLPVRKQFYSTAKKCKDEIKKIQDLLMSFG
  ILKPDLRIVFVHNKAVIWQKSRVSDHKMALMSVLGTAVMNNMESFQYHSEESQIYLSGFL
  PKCDADHSFTSLSTPERSFIFINSRPVHQKDILKLIRHHYNLKCLKESTRLYPVFFLKID
  VPTADVDVNLTPDKSQVLLQNKESVLIALENLMTTCYGPLPSTNSYENNKTDVSAADIVL
  SKTAETDVLFNKVESSGKNYSNVDTSVIPFQNDMHNDESGKNTDDCLNHQISIGDFGYGH
  CSSEISNIDKNTKNAFQDISMSNVSWENSQTEYSKTCFISSVKHTQSENGNKDHIDESGE
  NEEEAGLENSSEISADEWSRGNILKNSVGENIEPVKILVPEKSLPCKVSNNNYPIPEQMN
  LNEDSCNKKSNVIDNKSGKVTAYDLLSNRVIKKPMSASALFVQDHRPQFLIENPKTSLED
  ATLQIEELWKTLSEEEKLKYEEKATKDLERYNSQMKRAIEQESQMSLKDGRKKIKPTSAW
  NLAQKHKLKTSLSNQPKLDELLQSQIEKRRSQNIKMVQIPFSMKNLKINFKKQNKVDLEE
  KDEPCLIHNLRFPDAWLMTSKTEVMLLNPYRVEEALLFKRLLENHKLPAEPLEKPIMLTE
  SLFNGSHYLDVLYKMTADDQRYSGSTYLSDPRLTANGFKIKLIPGVSITENYLEIEGMAN
  CLPFYGVADLKEILNAILNRNAKEVYECRPRKVISYLEGEAVRLSRQLPMYLSKEDIQDI
  IYRMKHQFGNEIKECVHGRPFFHHLTYLPETT
• Function: Probably involved in the repair of mismatches in DNA.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lynch syndrome	DIS3IW5F	Refuted	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of PMS1 protein homolog 1 (PMS1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PMS1 protein homolog 1 (PMS1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PMS1 protein homolog 1 (PMS1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PMS1 protein homolog 1 (PMS1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PMS1 protein homolog 1 (PMS1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PMS1 protein homolog 1 (PMS1).	[7]
Selenium	DM25CGV	Approved	Selenium decreases the expression of PMS1 protein homolog 1 (PMS1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PMS1 protein homolog 1 (PMS1).	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of PMS1 protein homolog 1 (PMS1).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of PMS1 protein homolog 1 (PMS1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of PMS1 protein homolog 1 (PMS1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of PMS1 protein homolog 1 (PMS1).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of PMS1 protein homolog 1 (PMS1).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of PMS1 protein homolog 1 (PMS1).	[14]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of PMS1 protein homolog 1 (PMS1).	[15]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Exploring pradimicin-IRD antineoplastic mechanisms and related DNA repair pathways. Chem Biol Interact. 2023 Feb 1;371:110342. doi: 10.1016/j.cbi.2023.110342. Epub 2023 Jan 10.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [15] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.