Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMB4Y3R)

• DOT Name: Protein SLFN14 (SLFN14)
• Gene Name: SLFN14
• Related Disease:
  Inherited bleeding disorder, platelet-type
  Platelet-type bleeding disorder 20
  Atrial septal defect
  Thrombocytopenia
• UniProt ID: SLN14_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF17057 ; PF04326 ; PF21026
• Sequence:
  MESLKTDTEMPYPEVIVDVGRVIFGEENRKKMTNSCLKRSENSRIIRAICALLNSGGGVI
  KAEIDDKTYSYQCHGLGQDLETSFQKLLPSGSQKYLDYMQQGHNLLIFVKSWSPDVFSLP
  LRICSLRSNLYRRDVTSAINLSASSALELLREKGFRAQRGRPRVKKLHPQQVLNRCIQEE
  EDMRILASEFFKKDKLMYKEKLNFTESTHVEFKRFTTKKVIPRIKEMLPHYVSAFANTQG
  GYVLIGVDDKSKEVVGCKWEKVNPDLLKKEIENCIEKLPTFHFCCEKPKVNFTTKILNVY
  QKDVLDGYVCVIQVEPFCCVVFAEAPDSWIMKDNSVTRLTAEQWVVMMLDTQSAPPSLVT
  DYNSCLISSASSARKSPGYPIKVHKFKEALQRHLFPVTQEEVQFKPESLCKKLFSDHKEL
  EGLMKTLIHPCSQGIVIFSRSWAGDVGFRKEQNVLCDALLIAVNSPVVLYTILIDPNWPG
  GLEYARNTAHQLKQKLQTVGGYTGKVCIIPRLIHLSSTQSRPGEIPLRYPRSYRLADEEE
  MEDLLQALVVVSLSSRSLLSDQMGCEFFNLLIMEQSQLLSESLQKTRELFIYCFPGVRKT
  ALAIKIMEKIKDLFHCKPKEILYVCESDSLKDFVTQQTTCQAVTRKTFMQGEFLKIKHIV
  MDETENFCSKYGNWYMKAKNITHPKAKGTGSENLHHGILWLFLDPFQIHHADVNGLPPPS
  AQFPRKTITSGIHCALEIAKVMKEEMKRIKENPPSNMSPDTLALFSETAYEEATCAQALP
  GVCETKTNLTTEQIANYVARKCHSLFQCGYLPKDIAILCRRGEDRGRYRLALLKAMELIE
  THRPSEVVFSPATGVWGSHIVLDSIQQFSGLERTVVFGLSPECDQSEEFHKLCFASRAIK
  HLYLLYEKRAAY
• Function: [Protein SLFN14]: Shows no ribosome-associated and endoribonuclease activities; [C-terminally truncated SLFN14 endoribonuclease]: Displays polysome-associated endoribonuclease activity towards mRNAs and rRNAs. May play a role in RNA surveillance pathways by recognizing stalled ribosomes and triggering endonucleolytic cleavage of aberrant mRNAs (Probable). Cleaves different types of rRNAs and mRNAs in a magnesium- and manganese-dependent and ATP-independent manner. Involved in correct maturation of megakaryocytes and especially important for proplatelet extension.
• Tissue Specificity: Expressed in megakaryocytes and platelets (at protein level) . Weakly expressed in melanocytes and malignant melanoma cells .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Inherited bleeding disorder, platelet-type	DISIUNXT	Strong	Biomarker	[1]
Platelet-type bleeding disorder 20	DISNE5DD	Strong	Autosomal dominant	[2]
Atrial septal defect	DISJT76B	Limited	Genetic Variation	[3]
Thrombocytopenia	DISU61YW	Limited	Biomarker	[4]

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 increases the methylation of Protein SLFN14 (SLFN14).	[5]

References

• [1] SLFN14-related thrombocytopenia: identification within a large series of patients with inherited thrombocytopenia.Thromb Haemost. 2016 May 2;115(5):1076-9. doi: 10.1160/TH15-11-0884. Epub 2016 Jan 14.
• [2] SLFN14 mutations underlie thrombocytopenia with excessive bleeding and platelet secretion defects. J Clin Invest. 2015 Sep;125(9):3600-5. doi: 10.1172/JCI80347. Epub 2015 Aug 17.
• [3] Identification of Two Mutations in PCDHGA4 and SLFN14 Genes in an Atrial Septal Defect Family.Curr Med Sci. 2018 Dec;38(6):989-996. doi: 10.1007/s11596-018-1974-2. Epub 2018 Dec 7.
• [4] Role of the novel endoribonuclease SLFN14 and its disease-causing mutations in ribosomal degradation.RNA. 2018 Jul;24(7):939-949. doi: 10.1261/rna.066415.118. Epub 2018 Apr 20.
• [5] 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.