Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHW3DVC)

• DOT Name: Sarcolemmal membrane-associated protein (SLMAP)
• Synonyms: Sarcolemmal-associated protein
• Gene Name: SLMAP
• Related Disease:
  Diabetic retinopathy
  Non-insulin dependent diabetes
  Type-1/2 diabetes
  Autosomal recessive limb-girdle muscular dystrophy type 2B
  Cardiac failure
  Chronic obstructive pulmonary disease
  Congestive heart failure
  Dilated cardiomyopathy
  Duchenne muscular dystrophy
  Brugada syndrome
  Lateral meningocele syndrome
  Limb-mammary syndrome
• UniProt ID: SLMAP_HUMAN
• PDB ID: 6AKM; 6AR0; 6AR2
• Pfam ID: PF00498
• Sequence:
  MPSALAIFTCRPNSHPFQERHVYLDEPIKIGRSVARCRPAQNNATFDCKVLSRNHALVWF
  DHKTGKFYLQDTKSSNGTFINSQRLSRGSEESPPCEILSGDIIQFGVDVTENTRKVTHGC
  IVSTIKLFLPDGMEARLRSDVIHAPLPSPVDKVAANTPSMYSQELFQLSQYLQEALHREQ
  MLEQKLATLQRLLAITQEASDTSWQALIDEDRLLSRLEVMGNQLQACSKNQTEDSLRKEL
  IALQEDKHNYETTAKESLRRVLQEKIEVVRKLSEVERSLSNTEDECTHLKEMNERTQEEL
  RELANKYNGAVNEIKDLSDKLKVAEGKQEEIQQKGQAEKKELQHKIDEMEEKEQELQAKI
  EALQADNDFTNERLTALQVRLEHLQEKTLKECSSLEHLLSKSGGDCTFIHQFIECQKKLI
  VEGHLTKAVEETKLSKENQTRAKESDFSDTLSPSKEKSSDDTTDAQMDEQDLNEPLAKVS
  LLKDDLQGAQSEIEAKQEIQHLRKELIEAQELARTSKQKCFELQALLEEERKAYRNQVEE
  STKQIQVLQAQLQRLHIDTENLREEKDSEITSTRDELLSARDEILLLHQAAAKVASERDT
  DIASLQEELKKVRAELERWRKAASEYEKEITSLQNSFQLRCQQCEDQQREEATRLQGELE
  KLRKEWNALETECHSLKRENVLLSSELQRQEKELHNSQKQSLELTSDLSILQMSRKELEN
  QVGSLKEQHLRDSADLKTLLSKAENQAKDVQKEYEKTQTVLSELKLKFEMTEQEKQSITD
  ELKQCKNNLKLLREKGNNKPWPWMPMLAALVAVTAIVLYVPGLARASP
• Function: May play a role during myoblast fusion.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic retinopathy	DISHGUJM	Definitive	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Genetic Variation	[1]
Autosomal recessive limb-girdle muscular dystrophy type 2B	DISWWCL7	Strong	Genetic Variation	[2]
Cardiac failure	DISDC067	Strong	Biomarker	[3]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[4]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[3]
Dilated cardiomyopathy	DISX608J	Strong	Biomarker	[3]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[5]
Brugada syndrome	DISSGN0E	Supportive	Autosomal dominant	[6]
Lateral meningocele syndrome	DISG74RP	Limited	Biomarker	[7]
Limb-mammary syndrome	DIS7H4FP	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Sarcolemmal membrane-associated protein (SLMAP).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sarcolemmal membrane-associated protein (SLMAP).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sarcolemmal membrane-associated protein (SLMAP).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Sarcolemmal membrane-associated protein (SLMAP).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Sarcolemmal membrane-associated protein (SLMAP).	[12]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Sarcolemmal membrane-associated protein (SLMAP).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sarcolemmal membrane-associated protein (SLMAP).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Sarcolemmal membrane-associated protein (SLMAP).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sarcolemmal membrane-associated protein (SLMAP).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Sarcolemmal membrane-associated protein (SLMAP).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Sarcolemmal membrane-associated protein (SLMAP).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sarcolemmal membrane-associated protein (SLMAP).	[18]

References

• [1] Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population.J Transl Med. 2015 Feb 15;13:61. doi: 10.1186/s12967-015-0411-6.
• [2] Private dysferlin exon skipping mutation (c.5492G>A) with a founder effect reveals further alternative splicing involving exons 49-51.J Hum Genet. 2010 Aug;55(8):546-9. doi: 10.1038/jhg.2010.60. Epub 2010 Jun 10.
• [3] SLMAP-3 is downregulated in human dilated ventricles and its overexpression promotes cardiomyocyte response to adrenergic stimuli by increasing intracellular calcium.Can J Physiol Pharmacol. 2019 Jul;97(7):623-630. doi: 10.1139/cjpp-2018-0660. Epub 2019 Mar 11.
• [4] Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nat Genet. 2019 Mar;51(3):494-505. doi: 10.1038/s41588-018-0342-2. Epub 2019 Feb 25.
• [5] Differential YAP nuclear signaling in healthy and dystrophic skeletal muscle.Am J Physiol Cell Physiol. 2019 Jul 1;317(1):C48-C57. doi: 10.1152/ajpcell.00432.2018. Epub 2019 Apr 17.
• [6] Brugada Syndrome. 2005 Mar 31 [updated 2022 Aug 25]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [7] Expression of subtype-specific group 1 leiomyosarcoma markers in a wide variety of sarcomas by gene expression analysis and immunohistochemistry.Am J Surg Pathol. 2011 Apr;35(4):583-9. doi: 10.1097/PAS.0b013e318211abd6.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] 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.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [13] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [14] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [15] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [16] 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.
• [17] 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.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.