Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWXG2R8)

DOT Name Small regulatory polypeptide of amino acid response (SPAAR)
Gene Name SPAAR
Related Disease
Arthritis ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Hepatocellular carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Myocardial infarction ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Systemic sclerosis ( )
Advanced cancer ( )
Clear cell renal carcinoma ( )
Cutaneous melanoma ( )
Glioma ( )
Rectal carcinoma ( )
Renal cell carcinoma ( )
Squamous cell carcinoma ( )
UniProt ID
SPAR_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGAKAPRGPKVAQWAMETAVIGVVVVLFVVTVAITCVLCCFSCDSRAQDPQGGPGRSFTV
ATFRQEASLFTGPVRHAQPVPSAQDFWTFM
Function
[Isoform 2]: Negative regulator of amino acid sensing and mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels and amino acids. Negatively regulates mTORC1 activation by inhibiting recruitment of mTORC1 to lysosomes upon stimulation with amino acids: acts by promoting the formation of a tightly bound supercomplex composed of the lysosomal V-ATPase, Ragulator and Rag GTPases, preventing recruitment of mTORC1. Acts as a regulator of muscle regeneration following injury by regulating mTORC1 activation.
Tissue Specificity Highly expressed in lung, heart and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Arthritis DIST1YEL Strong Biomarker [1]
Coronary atherosclerosis DISKNDYU Strong Altered Expression [2]
Coronary heart disease DIS5OIP1 Strong Altered Expression [2]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [3]
Lung cancer DISCM4YA Strong Biomarker [3]
Lung carcinoma DISTR26C Strong Biomarker [3]
Myocardial infarction DIS655KI Strong Biomarker [4]
Neoplasm DISZKGEW Strong Biomarker [3]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [5]
Systemic sclerosis DISF44L6 Strong Biomarker [1]
Advanced cancer DISAT1Z9 Limited Biomarker [4]
Clear cell renal carcinoma DISBXRFJ Limited Altered Expression [6]
Cutaneous melanoma DIS3MMH9 Limited Altered Expression [7]
Glioma DIS5RPEH Limited Biomarker [3]
Rectal carcinoma DIS8FRR7 Limited Biomarker [8]
Renal cell carcinoma DISQZ2X8 Limited Altered Expression [6]
Squamous cell carcinoma DISQVIFL Limited Biomarker [9]
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⏷ Show the Full List of 17 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Small regulatory polypeptide of amino acid response (SPAAR). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Small regulatory polypeptide of amino acid response (SPAAR). [11]
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References

1 Prediction of progression of interstitial lung disease in patients with systemic sclerosis: the SPAR model.Ann Rheum Dis. 2018 Sep;77(9):1326-1332. doi: 10.1136/annrheumdis-2018-213201. Epub 2018 Jun 6.
2 Downregulation of linc00961 contributes to promote proliferation and inhibit apoptosis of vascular smooth muscle cell by sponging miR-367 in patients with coronary heart disease.Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8540-8550. doi: 10.26355/eurrev_201910_19168.
3 Small regulatory polypeptide of amino acid response negatively relates to poor prognosis and controls hepatocellular carcinoma progression via regulating microRNA-5581-3p/human cardiolipin synthase 1.J Cell Physiol. 2019 Aug;234(10):17589-17599. doi: 10.1002/jcp.28383. Epub 2019 Mar 1.
4 STAT1-avtiviated LINC00961 regulates myocardial infarction by the PI3K/AKT/GSK3 signaling pathway.J Cell Biochem. 2019 Aug;120(8):13226-13236. doi: 10.1002/jcb.28596. Epub 2019 Mar 19.
5 Long noncoding RNA LINC00961 inhibits cell invasion and metastasis in human non-small cell lung cancer.Biomed Pharmacother. 2018 Jan;97:1311-1318. doi: 10.1016/j.biopha.2017.11.062. Epub 2017 Dec 14.
6 LINC00961 restrains cancer progression via modulating epithelial-mesenchymal transition in renal cell carcinoma.J Cell Physiol. 2019 May;234(5):7257-7265. doi: 10.1002/jcp.27483. Epub 2018 Oct 26.
7 Linc00961 inhibits the proliferation and invasion of skin melanoma by targeting the miR?67/PTEN axis.Int J Oncol. 2019 Sep;55(3):708-720. doi: 10.3892/ijo.2019.4848. Epub 2019 Jul 25.
8 SPAR - a randomised, placebo-controlled phase II trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer: an AGITG clinical trial.BMC Cancer. 2019 Dec 17;19(1):1229. doi: 10.1186/s12885-019-6405-7.
9 LINC00961 suppresses cell proliferation and induces cell apoptosis in oral squamous cell carcinoma.Eur Rev Med Pharmacol Sci. 2019 Apr;23(8):3358-3365. doi: 10.26355/eurrev_201904_17699.
10 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.
11 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.