Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBXCS1L)

• DOT Name: Leucine-rich repeat-containing protein 39 (LRRC39)
• Synonyms: Myosin-interacting M-band-associated stress-responsive protein; Myomasp
• Gene Name: LRRC39
• Related Disease: Cardiomyopathy
• UniProt ID: LRC39_HUMAN
• Pfam ID: PF00560 ; PF13855
• Sequence:
  MTENVVCTGAVNAVKEVWEKRIKKLNEDLKREKEFQHKLVRIWEERVSLTKLREKVTRED
  GRVILKIEKEEWKTLPSSLLKLNQLQEWQLHRTGLLKIPEFIGRFQNLIVLDLSRNTISE
  IPPGIGLLTRLQELILSYNKIKTVPKELSNCASLEKLELAVNRDICDLPQELSNLLKLTH
  LDLSMNDFTTIPLAVLNMPALEWLDMGSNKLEQLPDTIERMQNLHTLWLQRNEITCLPQT
  ISNMKNLGTLVLSNNKLQDIPVCMEEMANLRFVNFRDNPLKLKVSLPPSEGTDEEEEREL
  FGLQFMHTYIQESRRRADHQVNGSTTLPISINTDG
• Function: Component of the sarcomeric M-band which plays a role in myocyte response to biomechanical stress. May regulate expression of other M-band proteins via an SRF-dependent pathway. Important for normal contractile function in heart.
• Tissue Specificity: Highly expressed in skeletal muscle and heart. Not detected in other tissues tested.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Leucine-rich repeat-containing protein 39 (LRRC39).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Leucine-rich repeat-containing protein 39 (LRRC39).	[3]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Leucine-rich repeat-containing protein 39 (LRRC39).	[4]

References

• [1] Myomasp/LRRC39, a heart- and muscle-specific protein, is a novel component of the sarcomeric M-band and is involved in stretch sensing.Circ Res. 2010 Nov 12;107(10):1253-64. doi: 10.1161/CIRCRESAHA.110.222372. Epub 2010 Sep 16.
• [2] 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.
• [3] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [4] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.