Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSJ3BJ2)

• DOT Name: Protein spinster homolog 1 (SPNS1)
• Synonyms: HSpin1; SPNS1; Spinster-like protein 1
• Gene Name: SPNS1
• Related Disease:
  Oral mucositis
  Abscess
  Analgesia
  Premature aging syndrome
  Niemann-Pick disease type C
  Niemann-Pick disease, type C1
  Neoplasm
  Post-traumatic stress disorder
  Rectal carcinoma
• UniProt ID: SPNS1_HUMAN
• Pfam ID: PF07690
• Sequence:
  MAGSDTAPFLSQADDPDDGPVPGTPGLPGSTGNPKSEEPEVPDQEGLQRITGLSPGRSAL
  IVAVLCYINLLNYMDRFTVAGVLPDIEQFFNIGDSSSGLIQTVFISSYMVLAPVFGYLGD
  RYNRKYLMCGGIAFWSLVTLGSSFIPGEHFWLLLLTRGLVGVGEASYSTIAPTLIADLFV
  ADQRSRMLSIFYFAIPVGSGLGYIAGSKVKDMAGDWHWALRVTPGLGVVAVLLLFLVVRE
  PPRGAVERHSDLPPLNPTSWWADLRALARNPSFVLSSLGFTAVAFVTGSLALWAPAFLLR
  SRVVLGETPPCLPGDSCSSSDSLIFGLITCLTGVLGVGLGVEISRRLRHSNPRADPLVCA
  TGLLGSAPFLFLSLACARGSIVATYIFIFIGETLLSMNWAIVADILLYVVIPTRRSTAEA
  FQIVLSHLLGDAGSPYLIGLISDRLRRNWPPSFLSEFRALQFSLMLCAFVGALGGAAFLG
  TAIFIEADRRRAQLHVQGLLHEAGSTDDRIVVPQRGRSTRVPVASVLI
• Function: Plays a critical role in the phospholipid salvage pathway from lysosomes to the cytosol. Mediates the rate-limiting, proton-dependent, lysosomal efflux of lysophospholipids, which can then be reacylated by acyltransferases in the endoplasmic reticulum to form phospholipids. Selective for zwitterionic headgroups such as lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), can also transport lysophosphatidylglycerol (LPG), but not other anionic lysophospholipids, sphingosine, nor sphingomyelin. Transports lysophospholipids with saturated, monounsaturated, and polyunsaturated fatty acids, such as 1-hexadecanoyl-sn-glycero-3-phosphocholine, 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine and 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, respectively. Can also transport lysoplasmalogen (LPC with a fatty alcohol) such as 1-(1Z-hexadecenyl)-sn-glycero-3-phosphocholine. Lysosomal LPC could function as intracellular signaling messenger. Essential player in lysosomal homeostasis. Crucial for cell survival under conditions of nutrient limitation. May be involved in necrotic or autophagic cell death.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Oral mucositis	DISS93V5	Definitive	Biomarker	[1]
Abscess	DISAP982	Strong	Biomarker	[2]
Analgesia	DISK3TVI	Strong	Biomarker	[3]
Premature aging syndrome	DIS51AGT	Strong	Biomarker	[4]
Niemann-Pick disease type C	DIS492ZO	moderate	Biomarker	[5]
Niemann-Pick disease, type C1	DIS9HUE3	moderate	Altered Expression	[5]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]
Post-traumatic stress disorder	DISHL1EY	Limited	Genetic Variation	[7]
Rectal carcinoma	DIS8FRR7	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein spinster homolog 1 (SPNS1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Protein spinster homolog 1 (SPNS1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein spinster homolog 1 (SPNS1).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Protein spinster homolog 1 (SPNS1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein spinster homolog 1 (SPNS1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein spinster homolog 1 (SPNS1).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein spinster homolog 1 (SPNS1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein spinster homolog 1 (SPNS1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein spinster homolog 1 (SPNS1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein spinster homolog 1 (SPNS1).	[16]

References

• [1] Low-level laser therapy dosimetry most used for oral mucositis due to radiotherapy for head and neck cancer: a systematic review and meta-analysis.Crit Rev Oncol Hematol. 2019 Jun;138:14-23. doi: 10.1016/j.critrevonc.2019.03.009. Epub 2019 Mar 31.
• [2] Apremilast for moderate hidradenitis suppurativa: Results of a randomized controlled trial.J Am Acad Dermatol. 2019 Jan;80(1):80-88. doi: 10.1016/j.jaad.2018.06.046. Epub 2018 Jul 3.
• [3] Intrathecal betamethasone for cancer pain: A study of its analgesic efficacy and safety.Acta Anaesthesiol Scand. 2019 May;63(5):659-667. doi: 10.1111/aas.13305. Epub 2018 Dec 7.
• [4] Autolysosome biogenesis and developmental senescence are regulated by both Spns1 and v-ATPase.Autophagy. 2017 Feb;13(2):386-403. doi: 10.1080/15548627.2016.1256934. Epub 2016 Nov 22.
• [5] L-leucine and SPNS1 coordinately ameliorate dysfunction of autophagy in mouse and human Niemann-Pick type C disease.Sci Rep. 2017 Nov 21;7(1):15944. doi: 10.1038/s41598-017-15305-9.
• [6] Metabolic Syndrome, as Defined Based on Parameters Including Visceral Fat Area, Predicts Complications After Surgery for Rectal Cancer.Obes Surg. 2020 Jan;30(1):319-326. doi: 10.1007/s11695-019-04163-1.
• [7] Is Use of a Psychological Workbook Associated With Improved Disabilities of the Arm, Shoulder and Hand Scores in Patients With Distal Radius Fracture?.Clin Orthop Relat Res. 2018 Apr;476(4):832-845. doi: 10.1007/s11999.0000000000000095.
• [8] 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.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] 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.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [13] 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.
• [14] 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.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.