Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMT7AII)

• DOT Name: Muscular LMNA-interacting protein (MLIP)
• Synonyms: Cardiac Isl1-interacting protein; CIP; Muscular-enriched A-type laminin-interacting protein
• Gene Name: MLIP
• Related Disease:
  Neoplasm
  Advanced cancer
  Attention deficit hyperactivity disorder
  Cardiac failure
  Cardiomyopathy
  Congestive heart failure
  Cryptococcosis
  Dyskeratosis congenita
  Early-onset anterior polar cataract
  Epithelial neoplasm
  Essential thrombocythemia
  Laryngeal carcinoma
  Lyme disease
  Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis
  Ovarian cancer
  Prostate cancer
  Prostate carcinoma
  Acute myelogenous leukaemia
  Methicillin-resistant staphylococci infection
  Acute leukaemia
  Breast cancer
  Breast carcinoma
  Gastroparesis
  Leukemia
  Neuroendocrine neoplasm
• UniProt ID: MLIP_HUMAN
• Pfam ID: PF15274
• Sequence:
  MLSEQGLLSDCGNNYFQMTSCILSGSIQTTPQVSAGGSEAKPLIFTFVPTVRRLPTHTQL
  ADTSKFLVKIPEESSDKSPETVNRSKSNDYLTLNAGSQQERDQAKLTCPSEVSGTILQER
  EFEANKLQGMQQSDLFKAEYVLIVDSEGEDEAASRKVEQGPPGGIGTAAVRPKSLAISSS
  LVSDVVRPKTQGTDLKTSSHPEMLHGMAPQQKHGQLTSSPTTSEQLACKPPAFSFVSPTN
  PNTPPDPVNLEGASVLEEFHTRRLDVGGAVVEESATYFQTTAHSTPFSASKGTSSTLLFP
  HSTQLSGSNLPSSTAADPKPGLTSEVLKKTTLTSHVLSHGESPRTSSSPPSSSASLKSNS
  ASYIPVRIVTHSLSPSPKPFTSSFHGSSSTICSQMSSSGNLSKSGVKSPVPSRLALLTAI
  LKSNPSHQRPFSPASCPTFSLNSPASSTLTLDQKEKQTPPTPKKSLSSCSLRAGSPDQGE
  LQVSELTQQSFHLPVFTKSTPLSQAPSLSPTKQASSSLASMNVERTPSPTLKSNTMLSLL
  QTSTSSSVGLPPVPPSSSLSSLKSKQDGDLRGPENPRNIHTYPSTLASSALSSLSPPINQ
  RATFSSSEKCFHPSPALSSLINRSKRASSQLSGQELNPSALPSLPVSSADFASLPNLRSS
  SLPHANLPTLVPQLSPSALHPHCGSGTLPSRLGKSESTTPNHRSPVSTPSLPISLTRTEE
  LISPCALSMSTGPENKKSKQYKTKSSYKAFAAIPTNTLLLEQKALDEPAKTESVSKDNTL
  EPPVELYFPAQLRQQTEELCATIDKVLQDSLSMHSSDSPSRSPKTLLGSDTVKTPTTLPR
  AAGRETKYANLSSPSSTVSESQLTKPGVIRPVPVKSRILLKKEEEVYEPNPFSKYLEDNS
  DLFSEQDVTVPPKPVSLHPLYQTKLYPPAKSLLHPQTLSHADCLAPGPFSHLSFSLSDEQ
  ENSHTLLSHNACNKLSHPMVAIPEHEALDSKEQ
• Function: Required for myoblast differentiation into myotubes, possibly acting as a transcriptional regulator of the myogenic program. Required for cardiac adaptation to stress through integrated regulation of the AKT/mTOR pathways and FOXO1. Regulates cardiac homeostasis and plays a role in the protection against cardiac hypertrophy. Binds chromatin. May act as a transcriptional cofactor for ISL1, repressing its transcriptional activity. May also repress MYOCD transcriptional activity.
• Tissue Specificity: Predominantly expressed in the heart and skeletal muscle . Also detected in liver .; [Isoform 2]: Expressed in skeletal muscle.; [Isoform 3]: Expressed in skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[3]
Cardiac failure	DISDC067	Strong	Genetic Variation	[4]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[4]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[4]
Cryptococcosis	DISDYDTK	Strong	Biomarker	[5]
Dyskeratosis congenita	DISSXV0K	Strong	Biomarker	[6]
Early-onset anterior polar cataract	DISTOPIY	Strong	Biomarker	[7]
Epithelial neoplasm	DIS0T594	Strong	Altered Expression	[8]
Essential thrombocythemia	DISWWK11	Strong	Biomarker	[9]
Laryngeal carcinoma	DISNHCIV	Strong	Altered Expression	[10]
Lyme disease	DISO70G5	Strong	Biomarker	[11]
Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis	DISSEAAM	Strong	Autosomal recessive	[12]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[13]
Prostate cancer	DISF190Y	Strong	Biomarker	[14]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[15]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[16]
Acute leukaemia	DISDQFDI	Limited	Altered Expression	[17]
Breast cancer	DIS7DPX1	Limited	Biomarker	[18]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[18]
Gastroparesis	DISDW0SR	Limited	Genetic Variation	[19]
Leukemia	DISNAKFL	Limited	Posttranslational Modification	[17]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[20]

9 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 Muscular LMNA-interacting protein (MLIP).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Muscular LMNA-interacting protein (MLIP).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Muscular LMNA-interacting protein (MLIP).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Muscular LMNA-interacting protein (MLIP).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Muscular LMNA-interacting protein (MLIP).	[25]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Muscular LMNA-interacting protein (MLIP).	[26]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Muscular LMNA-interacting protein (MLIP).	[27]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Muscular LMNA-interacting protein (MLIP).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Muscular LMNA-interacting protein (MLIP).	[29]

References

• [1] Long-term downregulation of Polo-like kinase 1 increases the cyclin-dependent kinase inhibitor p21(WAF1/CIP1).Cell Cycle. 2009 Feb 1;8(3):460-72. doi: 10.4161/cc.8.3.7651. Epub 2009 Feb 18.
• [2] Ciz1 promotes tumorigenicity of prostate carcinoma cells.Front Biosci (Landmark Ed). 2015 Jan 1;20(4):705-15. doi: 10.2741/4331.
• [3] A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder.Biol Psychiatry. 2018 Jun 15;83(12):1044-1053. doi: 10.1016/j.biopsych.2017.11.026. Epub 2017 Dec 2.
• [4] Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis.J Clin Invest. 2015 Nov 2;125(11):4122-34. doi: 10.1172/JCI82423. Epub 2015 Oct 5.
• [5] Mycobacterium doricum sp. nov.Int J Syst Evol Microbiol. 2001 Nov;51(Pt 6):2007-2012. doi: 10.1099/00207713-51-6-2007.
• [6] The p53/p21(WAF/CIP) pathway mediates oxidative stress and senescence in dyskeratosis congenita cells with telomerase insufficiency.Antioxid Redox Signal. 2011 Mar 15;14(6):985-97. doi: 10.1089/ars.2010.3444. Epub 2011 Jan 17.
• [7] The changing epidemiology of community-acquired pneumonia: nationwide register-based study in Sweden.J Intern Med. 2019 Dec;286(6):689-701. doi: 10.1111/joim.12956. Epub 2019 Aug 13.
• [8] E6AP mediates regulated proteasomal degradation of the nuclear receptor coactivator amplified in breast cancer 1 in immortalized cells.Cancer Res. 2006 Sep 1;66(17):8680-6. doi: 10.1158/0008-5472.CAN-06-0557.
• [9] Clonal hemopoiesis and risk of thrombosis in young female patients with essential thrombocythemia.Exp Hematol. 2001 Jun;29(6):670-6. doi: 10.1016/s0301-472x(01)00640-3.
• [10] Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer.J Clin Oncol. 1999 Oct;17(10):3150-9. doi: 10.1200/JCO.1999.17.10.3150.
• [11] Genomic and phenotypic characterization of Borrelia afzelii BO23 and Borrelia garinii CIP 103362.PLoS One. 2018 Jun 26;13(6):e0199641. doi: 10.1371/journal.pone.0199641. eCollection 2018.
• [12] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [13] -Estradiol-dependent activation of the JAK/STAT pathway requires p/CIP and CARM1.Biochim Biophys Acta. 2013 Jun;1833(6):1463-75. doi: 10.1016/j.bbamcr.2013.02.009. Epub 2013 Feb 20.
• [14] PI3K-Akt signaling is involved in the regulation of p21(WAF/CIP) expression and androgen-independent growth in prostate cancer cells.Int J Oncol. 2006 Jan;28(1):245-51.
• [15] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [16] Synergistic antibacterial effect of Bi(2)S(3) nanospheres combined with ineffective antibiotic gentamicin against methicillin-resistant Staphylococcus aureus.J Inorg Biochem. 2017 Mar;168:38-45. doi: 10.1016/j.jinorgbio.2016.12.005. Epub 2016 Dec 10.
• [17] Epigenetic inactivation of the CIP/KIP cell-cycle control pathway in acute leukemias.Am J Hematol. 2005 Dec;80(4):282-7. doi: 10.1002/ajh.20503.
• [18] The KIP/CIP family members p21^{Waf1/Cip1} and p57^{Kip2} as diagnostic markers for breast cancer.Cancer Biomark. 2017;18(4):413-423. doi: 10.3233/CBM-160308.
• [19] Diagnosis and treatment of chronic gastroparesis and chronic intestinal pseudo-obstruction.Gastroenterol Clin North Am. 2003 Jun;32(2):619-58. doi: 10.1016/s0889-8553(03)00028-1.
• [20] BRD4 inhibitor IBET upregulates p27kip/cip protein stability in neuroendocrine tumor cells.Cancer Biol Ther. 2017 Apr 3;18(4):229-236. doi: 10.1080/15384047.2017.1294291. Epub 2017 Mar 10.
• [21] 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.
• [22] 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.
• [23] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [24] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [25] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [26] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [27] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [28] 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.
• [29] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.