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
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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]
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⏷ Show the Full List of 11 Drug(s)

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.