Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8F009J)

• DOT Name: Smoothelin-like protein 1 (SMTNL1)
• Gene Name: SMTNL1
• Related Disease:
  Advanced cancer
  Primary cutaneous peripheral T-cell lymphoma not otherwise specified
• UniProt ID: SMTL1_HUMAN
• Pfam ID: PF00307
• Sequence:
  MEQKEGKLSEDGTTVSPAADNPEMSGGGAPAEETKGTAGKAINEGPPTESGKQEKAPAED
  GMSAELQGEANGLDEVKVESQREAGGKEDAEAELKKEDGEKEETTVGSQEMTGRKEETKS
  EPKEAEEKESTLASEKQKAEEKEAKPESGQKADANDRDKPEPKATVEEEDAKTASQEETG
  QRKECSTEPKEKATDEEAKAESQKAVVEDEAKAEPKEPDGKEEAKHGAKEEADAKEEAED
  AEEAEPGSPSEEQEQDVEKEPEGGAGVIPSSPEEWPESPTGEGHNLSTDGLGPDCVASGQ
  TSPSASESSPSDVPQSPPESPSSGEKKEKAPERRVSAPARPRGPRAQNRKAIVDKFGGAA
  SGPTALFRNTKAAGAAIGGVKNMLLEWCRAMTKKYEHVDIQNFSSSWSSGMAFCALIHKF
  FPDAFDYAELDPAKRRHNFTLAFSTAEKLADCAQLLDVDDMVRLAVPDSKCVYTYIQELY
  RSLVQKGLVKTKKK
• Function: Plays a role in the regulation of contractile properties of both striated and smooth muscles. When unphosphorylated, may inhibit myosin dephosphorylation. Phosphorylation at Ser-299 reduces this inhibitory activity.
• Tissue Specificity: Expressed in striated muscles, specifically in type 2a fibers (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Smoothelin-like protein 1 (SMTNL1).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Smoothelin-like protein 1 (SMTNL1).	[4]

References

• [1] CanDrA: cancer-specific driver missense mutation annotation with optimized features.PLoS One. 2013 Oct 30;8(10):e77945. doi: 10.1371/journal.pone.0077945. eCollection 2013.
• [2] Concurrent Mutations in ATM and Genes Associated with Common Chain Signaling in Peripheral T Cell Lymphoma.PLoS One. 2015 Nov 4;10(11):e0141906. doi: 10.1371/journal.pone.0141906. eCollection 2015.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.