Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT89YD2E)

DOT Name Secreted Ly-6/uPAR-related protein 1 (SLURP1)
Synonyms SLURP-1; ARS component B; ARS(component B)-81/S; Anti-neoplastic urinary protein; ANUP
Gene Name SLURP1
Related Disease
Colorectal carcinoma ( )
Melanocytic nevus ( )
Precancerous condition ( )
Adult glioblastoma ( )
Age-related macular degeneration ( )
Autoimmune disease ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Charcot marie tooth disease ( )
Cowden disease ( )
Differentiated thyroid carcinoma ( )
Diffuse palmoplantar keratoderma ( )
Fatty liver disease ( )
Glioblastoma multiforme ( )
Glycogen storage disease type II ( )
Hailey-Hailey disease ( )
Leukodystrophy ( )
Lung adenocarcinoma ( )
Mal de Meleda ( )
Malignant soft tissue neoplasm ( )
Matthew-Wood syndrome ( )
Metastatic malignant neoplasm ( )
Pancreatic cancer ( )
Pancytopenia ( )
Plasmodium falciparum malaria ( )
Polymyositis ( )
Psoriasis ( )
Rheumatoid arthritis ( )
Rothmund-Thomson syndrome ( )
Sarcoma ( )
Systemic lupus erythematosus ( )
Thrombocytopenia ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid tumor ( )
Ulcerative colitis ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Erythrokeratoderma ( )
Myositis disease ( )
Hereditary palmoplantar keratoderma, Gamborg-Nielsen type ( )
Advanced cancer ( )
Arthritis ( )
Asthma ( )
Connective tissue disorder ( )
Dermatomyositis ( )
Melanoma ( )
Neoplasm ( )
UniProt ID
SLUR1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
6ZZE; 6ZZF
Pfam ID
PF00021
Sequence
MASRWAVQLLLVAAWSMGCGEALKCYTCKEPMTSASCRTITRCKPEDTACMTTLVTVEAE
YPFNQSPVVTRSCSSSCVATDPDSIGAAHLIFCCFRDLCNSEL
Function
Has an antitumor activity. Was found to be a marker of late differentiation of the skin. Implicated in maintaining the physiological and structural integrity of the keratinocyte layers of the skin. In vitro down-regulates keratinocyte proliferation; the function may involve the proposed role as modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro inhibits alpha-7-dependent nAChR currents in an allosteric manner. In T cells may be involved in regulation of intracellular Ca(2+) signaling. Seems to have an immunomodulatory function in the cornea. The function may implicate a possible role as a scavenger receptor for PLAU thereby blocking PLAU-dependent functions of PLAUR such as in cell migration and proliferation.
Tissue Specificity
Granulocytes. Expressed in skin. Predominantly expressed in the granular layer of skin, notably the acrosyringium. Identified in several biological fluids such as sweat, saliva, tears, plasma and urine.
KEGG Pathway
Neuroactive ligand-receptor interaction (hsa04080 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colorectal carcinoma DIS5PYL0 Definitive Genetic Variation [1]
Melanocytic nevus DISYS32D Definitive Altered Expression [2]
Precancerous condition DISV06FL Definitive Altered Expression [2]
Adult glioblastoma DISVP4LU Strong Biomarker [3]
Age-related macular degeneration DIS0XS2C Strong Genetic Variation [4]
Autoimmune disease DISORMTM Strong Biomarker [5]
Bladder cancer DISUHNM0 Strong Biomarker [3]
Breast cancer DIS7DPX1 Strong Genetic Variation [6]
Breast carcinoma DIS2UE88 Strong Genetic Variation [6]
Charcot marie tooth disease DIS3BT2L Strong Genetic Variation [7]
Cowden disease DISMYKCE Strong Biomarker [8]
Differentiated thyroid carcinoma DIS1V20Y Strong Biomarker [9]
Diffuse palmoplantar keratoderma DIS6O9JS Strong Biomarker [10]
Fatty liver disease DIS485QZ Strong Biomarker [11]
Glioblastoma multiforme DISK8246 Strong Biomarker [3]
Glycogen storage disease type II DISXZPBC Strong Genetic Variation [4]
Hailey-Hailey disease DISCM9SG Strong Biomarker [12]
Leukodystrophy DISVY1TT Strong Genetic Variation [13]
Lung adenocarcinoma DISD51WR Strong Genetic Variation [3]
Mal de Meleda DISVLL9A Strong Autosomal recessive [14]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [3]
Matthew-Wood syndrome DISA7HR7 Strong Biomarker [15]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [9]
Pancreatic cancer DISJC981 Strong Biomarker [15]
Pancytopenia DISVKEHV Strong Biomarker [16]
Plasmodium falciparum malaria DIS3Q9KF Strong Biomarker [17]
Polymyositis DIS5DHFP Strong Biomarker [18]
Psoriasis DIS59VMN Strong Biomarker [19]
Rheumatoid arthritis DISTSB4J Strong Biomarker [20]
Rothmund-Thomson syndrome DISGVBCV Strong Biomarker [12]
Sarcoma DISZDG3U Strong Biomarker [3]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [20]
Thrombocytopenia DISU61YW Strong Biomarker [16]
Thyroid cancer DIS3VLDH Strong Genetic Variation [21]
Thyroid gland carcinoma DISMNGZ0 Strong Genetic Variation [21]
Thyroid tumor DISLVKMD Strong Genetic Variation [21]
Ulcerative colitis DIS8K27O Strong Genetic Variation [8]
Urinary bladder cancer DISDV4T7 Strong Biomarker [3]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [3]
Erythrokeratoderma DISQGG08 moderate Genetic Variation [22]
Myositis disease DISCIXF0 moderate Biomarker [23]
Hereditary palmoplantar keratoderma, Gamborg-Nielsen type DIS8E1MP Supportive Autosomal recessive [24]
Advanced cancer DISAT1Z9 Limited Biomarker [23]
Arthritis DIST1YEL Limited Biomarker [25]
Asthma DISW9QNS Limited Altered Expression [26]
Connective tissue disorder DISKXBS3 Limited Biomarker [27]
Dermatomyositis DIS50C5O Limited Biomarker [23]
Melanoma DIS1RRCY Limited Biomarker [2]
Neoplasm DISZKGEW Limited Biomarker [15]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Regulation of Drug Effects of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Acetylcholine DMDF79Z Approved Secreted Ly-6/uPAR-related protein 1 (SLURP1) increases the abundance of Acetylcholine. [30]
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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 Secreted Ly-6/uPAR-related protein 1 (SLURP1). [28]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Secreted Ly-6/uPAR-related protein 1 (SLURP1). [29]
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References

1 Rare MDM4 gene amplification in colorectal cancer: The principle of a mutually exclusive relationship between MDM alteration and TP53 inactivation is not applicable.Oncol Rep. 2011 Jul;26(1):49-54. doi: 10.3892/or.2011.1270. Epub 2011 Apr 18.
2 SLURP-1 is mutated in Mal de Meleda, a potential molecular signature for melanoma and a putative squamous lineage tumor suppressor gene.Int J Dermatol. 2018 Feb;57(2):162-170. doi: 10.1111/ijd.13850. Epub 2017 Dec 12.
3 When the guardian sleeps: Reactivation of the p53 pathway in cancer.Mutat Res Rev Mutat Res. 2017 Jul;773:1-13. doi: 10.1016/j.mrrev.2017.02.003. Epub 2017 Feb 17.
4 Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD).Prog Retin Eye Res. 2010 May;29(3):169-90. doi: 10.1016/j.preteyeres.2010.02.002. Epub 2010 Mar 3.
5 EPRS is a critical regulator of cell proliferation and estrogen signaling in ER+ breast cancer.Oncotarget. 2016 Oct 25;7(43):69592-69605. doi: 10.18632/oncotarget.11870.
6 Potentially functional polymorphisms in aminoacyl-tRNA synthetases genes are associated with breast cancer risk in a Chinese population.Mol Carcinog. 2015 Jul;54(7):577-83. doi: 10.1002/mc.22128. Epub 2014 Feb 9.
7 Dimerization is required for GARS-mediated neurotoxicity in dominant CMT disease.Hum Mol Genet. 2016 Apr 15;25(8):1528-42. doi: 10.1093/hmg/ddw031. Epub 2016 Feb 7.
8 Monocyte-derived macrophages from Crohn's disease patients are impaired in the ability to control intracellular adherent-invasive Escherichia coli and exhibit disordered cytokine secretion profile.J Crohns Colitis. 2015 May;9(5):410-20. doi: 10.1093/ecco-jcc/jjv053. Epub 2015 Mar 24.
9 Distinguishing synchronous from metachronous manifestation of distant metastases: a prognostic feature in differentiated thyroid carcinoma.Eur J Nucl Med Mol Imaging. 2017 Feb;44(2):190-195. doi: 10.1007/s00259-016-3485-3. Epub 2016 Aug 16.
10 IL-22/STAT3-Induced Increases in SLURP1 Expression within Psoriatic Lesions Exerts Antimicrobial Effects against Staphylococcus aureus.PLoS One. 2015 Oct 16;10(10):e0140750. doi: 10.1371/journal.pone.0140750. eCollection 2015.
11 Sfrp5 interacts with Slurp1 to regulate the accumulation of triglycerides in hepatocyte steatosis model.Biochem Biophys Res Commun. 2019 Apr 30;512(2):256-262. doi: 10.1016/j.bbrc.2019.03.035. Epub 2019 Mar 15.
12 Palmoplantar keratoderma along with neuromuscular and metabolic phenotypes in Slurp1-deficient mice.J Invest Dermatol. 2014 Jun;134(6):1589-1598. doi: 10.1038/jid.2014.19. Epub 2014 Jan 17.
13 Biallelic KARS pathogenic variants cause an early-onset progressive leukodystrophy.Brain. 2019 Mar 1;142(3):560-573. doi: 10.1093/brain/awz001.
14 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
15 Endogenous CHRNA7-ligand SLURP1 as a potential tumor suppressor and anti-nicotinic factor in pancreatic cancer.Oncotarget. 2018 Jan 24;9(14):11734-11751. doi: 10.18632/oncotarget.24312. eCollection 2018 Feb 20.
16 A New Zealand White rabbit model of thrombocytopenia and coagulopathy following total body irradiation across the dose range to induce the hematopoietic-subsyndrome of acute radiation syndrome.Int J Radiat Biol. 2021;97(sup1):S19-S31. doi: 10.1080/09553002.2019.1668981. Epub 2020 Oct 5.
17 Comparison of the Pharmacokinetics and Ex Vivo Antimalarial Activities of Artesunate-Amodiaquine and Artemisinin-Piperaquine in Healthy Volunteers for Preselection Malaria Therapy.Am J Trop Med Hyg. 2018 Jul;99(1):65-72. doi: 10.4269/ajtmh.17-0434. Epub 2018 May 3.
18 Distinct profiles of myositis-specific autoantibodies in Chinese and Japanese patients with polymyositis/dermatomyositis.Clin Rheumatol. 2015 Sep;34(9):1627-31. doi: 10.1007/s10067-015-2935-9. Epub 2015 Apr 24.
19 Lesional upregulation of SLURP1 immunostaining parallels disease severity in psoriasis vulgaris patients.J Dtsch Dermatol Ges. 2018 Nov;16(11):1329-1337. doi: 10.1111/ddg.13682.
20 Proinflammatory Differentiation of Macrophages Through Microparticles That Form Immune Complexes Leads to T- and B-Cell Activation in Systemic Autoimmune Diseases.Front Immunol. 2019 Aug 28;10:2058. doi: 10.3389/fimmu.2019.02058. eCollection 2019.
21 Thyroid tumorigenesis and molecular markers in thyroid cancer.Curr Opin Oncol. 2010 Jan;22(1):23-9. doi: 10.1097/CCO.0b013e328333846f.
22 SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda.Br J Dermatol. 2011 Jan;164(1):47-53. doi: 10.1111/j.1365-2133.2010.10059.x. Epub 2010 Nov 23.
23 Current understanding and recent advances in myositis-specific and -associated autoantibodies detected in patients with dermatomyositis.Expert Rev Clin Immunol. 2020 Jan;16(1):79-89. doi: 10.1080/1744666X.2019.1699059. Epub 2019 Dec 8.
24 Palmoplantar keratoderma of the Gamborg-Nielsen type is caused by mutations in the SLURP1 gene and represents a variant of Mal de Meleda. Acta Derm Venereol. 2014 Nov;94(6):707-10. doi: 10.2340/00015555-1840.
25 Elevated serum nitric oxide levels in patients with inflammatory arthritis associated with co-expression of inducible nitric oxide synthase and protein kinase C-eta in peripheral blood monocyte-derived macrophages.J Rheumatol. 2003 Dec;30(12):2529-34.
26 Down-regulation of secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1), an endogenous allosteric alpha7 nicotinic acetylcholine receptor modulator, in murine and human asthmatic conditions.Biochem Biophys Res Commun. 2010 Aug 6;398(4):713-8. doi: 10.1016/j.bbrc.2010.07.006. Epub 2010 Jul 16.
27 The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies.Respir Med. 2017 Jun;127:57-64. doi: 10.1016/j.rmed.2017.04.007. Epub 2017 Apr 15.
28 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.
29 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.
30 SLURP-1, an endogenous 7 nicotinic acetylcholine receptor allosteric ligand, is expressed in CD205(+) dendritic cells in human tonsils and potentiates lymphocytic cholinergic activity. J Neuroimmunol. 2014 Feb 15;267(1-2):43-9. doi: 10.1016/j.jneuroim.2013.12.003. Epub 2013 Dec 11.