Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJI0HM9)

• DOT Name: Protein MMS22-like (MMS22L)
• Synonyms: Methyl methanesulfonate-sensitivity protein 22-like
• Gene Name: MMS22L
• Related Disease:
  Chronic obstructive pulmonary disease
  Esophageal cancer
  Breast cancer
  Breast carcinoma
• UniProt ID: MMS22_HUMAN
• Pfam ID: PF14911 ; PF14910
• Sequence:
  MENCSAASTFLTDSLELELGTEWCKPPYFSCAVDNRGGGKHFSGESYLCSGALKRLILNL
  DPLPTNFEEDTLEIFGIQWVTETALVNSSRELFHLFRQQLYNLETLLQSSCDFGKVSTLH
  CKADNIRQQCVLFLHYVKVFIFRYLKVQNAESHVPVHPYEALEAQLPSVLIDELHGLLLY
  IGHLSELPSVNIGAFVNQNQIKLFPPSWHLLHLHLDIHWLVLEILYMLGEKLKQVVYGHQ
  FMNLASDNLTNISLFEEHCETLLCDLISLSLNRYDKVRSSESLMSDQCPCLCIKELWVLL
  IHLLDHRSKWFVSESFWNWLNKLLKTLLEKSSDRRRSSMPVIQSRDPLGFSWWIITHVAS
  FYKFDRHGVPDEMRKVESNWNFVEELLKKSISVQGVILEEQLRMYLHCCLTLCDFWEPNI
  AIVTILWEYYSKNLNSSFSISWLPFKGLANTMKSPLSMLEMVKTCCCDKQDQELYKSSSS
  YTIFLCILAKVVKKAMKSNGPHPWKQVKGRIYSKFHQKRMEELTEVGLQNFFSLFLLLAA
  VAEVEDVASHVLDLLNFLKPAFVTSQRALIWKGHMAFLLMYAQKNLDIGVLAEKFSCAFR
  EKAKEFLVSKNEEMVQRQTIWTLLSIYIDGVQEVFETSYCLYPSHEKLLNDGFSMLLRAC
  RESELRTVLSFLQAVLARIRSMHQQLCQELQRDNVDLFVQSSLSAKERHLAAVASALWRH
  FFSFLKSQRMSQVVPFSQLADAAADFTLLAMDMPSTAPSDFQPQPVISIIQLFGWDDIIC
  PQVVARYLSHVLQNSTLCEALSHSGYVSFQALTVRSWIRCVLQMYIKNLSGPDDLLIDKN
  LEEAVEKEYMKQLVKLTRLLFNLSEVKSIFSKAQVEYLSISEDPKKALVRFFEAVGVTYG
  NVQTLSDKSAMVTKSLEYLGEVLKYIKPYLGKKVFSAGLQLTYGMMGILVKSWAQIFATS
  KAQKLLFRIIDCLLLPHAVLQQEKELPAPMLSAIQKSLPLYLQGMCIVCCQSQNPNAYLN
  QLLGNVIEQYIGRFLPASPYVSDLGQHPVLLALRNTATIPPISSLKKCIVQVIRKSYLEY
  KGSSPPPRLASILAFILQLFKETNTDIYEVELLLPGILKCLVLVSEPQVKRLATENLQYM
  VKACQVGSEEEPSSQLTSVFRQFIQDYGMRYYYQVYSILETVATLDQQVVIHLISTLTQS
  LKDSEQKWGLGRNIAQREAYSKLLSHLGQMGQDEMQRLENDNT
• Function: Component of the MMS22L-TONSL complex, a complex that promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication. It mediates the assembly of RAD51 filaments on single-stranded DNA (ssDNA): the MMS22L-TONSL complex is recruited to DSBs following histone replacement by histone chaperones and eviction of the replication protein A complex (RPA/RP-A) from DSBs. Following recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of RAD51 filaments and subsequent homologous recombination. Within the complex, MMS22L acts by binding ssDNA.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[1]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Limited	Biomarker	[3]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[3]

11 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 Protein MMS22-like (MMS22L).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein MMS22-like (MMS22L).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein MMS22-like (MMS22L).	[5]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Protein MMS22-like (MMS22L).	[6]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Protein MMS22-like (MMS22L).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Protein MMS22-like (MMS22L).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein MMS22-like (MMS22L).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein MMS22-like (MMS22L).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein MMS22-like (MMS22L).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein MMS22-like (MMS22L).	[12]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Protein MMS22-like (MMS22L).	[13]

References

• [1] A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.BMC Genet. 2015 Dec 3;16:138. doi: 10.1186/s12863-015-0299-4.
• [2] Identification of a novel oncogene, MMS22L, involved in lung and esophageal carcinogenesis.Int J Oncol. 2012 Oct;41(4):1285-96. doi: 10.3892/ijo.2012.1589. Epub 2012 Aug 10.
• [3] Fresh and ozonized black carbon promoted DNA damage and repair responses in A549 cells.Toxicol Res (Camb). 2018 Nov 30;8(2):180-187. doi: 10.1039/c8tx00281a. eCollection 2019 Mar 1.
• [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] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [7] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [8] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.