Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQH8HJ5)

DOT Name Spermatogenic leucine zipper protein 1 (SPZ1)
Synonyms Testis-specific protein 1; Testis-specific protein NYD-TSP1
Gene Name SPZ1
Related Disease
Adenocarcinoma ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Lung adenocarcinoma ( )
Neuroblastoma ( )
Ovarian neoplasm ( )
Adenoma ( )
Advanced cancer ( )
Bladder cancer ( )
Breast neoplasm ( )
Carcinoma ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Clear cell renal carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Epithelial ovarian cancer ( )
Glaucoma/ocular hypertension ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
High blood pressure ( )
Hyperglycemia ( )
Liver cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Metastatic malignant neoplasm ( )
Nasopharyngeal carcinoma ( )
Non-insulin dependent diabetes ( )
Obesity ( )
Renal cell carcinoma ( )
Rheumatoid arthritis ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Vascular disease ( )
Breast carcinoma ( )
Melanoma ( )
Neoplasm ( )
Adult glioblastoma ( )
Bone osteosarcoma ( )
Colitis ( )
Gastric cancer ( )
Gastric neoplasm ( )
Hereditary diffuse gastric adenocarcinoma ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
UniProt ID
SPZ1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MASSAKSAEMPTISKTVNPTPDPHQEYLDPRITIALFEIGSHSPSSWGSLPFLKNSSHQV
TEQQTAQKFNNLLKEIKDILKNMAGFEEKITEAKELFEETNITEDVSAHKENIRGLDKIN
EMLSTNLPVSLAPEKEDNEKKQEMILETNITEDVSAHKENIRGLDKINEMLSTNLPVSLA
PEKEDNEKKQQMIMENQNSENTAQVFARDLVNRLEEKKVLNETQQSQEKAKNRLNVQEET
MKIRNNMEQLLQEAEHWSKQHTELSKLIKSYQKSQKDISETLGNNGVGFQTQPNNEVSAK
HELEEQVKKLSHDTYSLQLMAALLENECQILQQRVEILKELHHQKQGTLQEKPIQINYKQ
DKKNQKPSEAKKVEMYKQNKQAMKGTFWKKDRSCRSLDVCLNKKACNTQFNIHVARKALR
GKMRSASSLR
Function
Transcription factor that binds to the DNA sequence 5'-CANNTG-3'(E box) and the G-box motif. May play an important role in the regulation of cell proliferation and differentiation during spermatogenesis.
Tissue Specificity Specifically and strongly expressed in the testis. Expressed in several tumor cell lines.

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Definitive Biomarker [1]
Arteriosclerosis DISK5QGC Definitive Altered Expression [2]
Atherosclerosis DISMN9J3 Definitive Altered Expression [2]
Lung adenocarcinoma DISD51WR Definitive Altered Expression [3]
Neuroblastoma DISVZBI4 Definitive Posttranslational Modification [4]
Ovarian neoplasm DISEAFTY Definitive Altered Expression [5]
Adenoma DIS78ZEV Strong Biomarker [6]
Advanced cancer DISAT1Z9 Strong Biomarker [7]
Bladder cancer DISUHNM0 Strong Altered Expression [8]
Breast neoplasm DISNGJLM Strong Altered Expression [9]
Carcinoma DISH9F1N Strong Altered Expression [10]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Strong Biomarker [11]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [12]
Colon cancer DISVC52G Strong Biomarker [6]
Colon carcinoma DISJYKUO Strong Biomarker [6]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [13]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [14]
Glaucoma/ocular hypertension DISLBXBY Strong Biomarker [15]
Glioblastoma multiforme DISK8246 Strong Biomarker [16]
Glioma DIS5RPEH Strong Altered Expression [17]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [18]
High blood pressure DISY2OHH Strong Biomarker [19]
Hyperglycemia DIS0BZB5 Strong Altered Expression [20]
Liver cancer DISDE4BI Strong Biomarker [11]
Lung cancer DISCM4YA Strong Biomarker [21]
Lung carcinoma DISTR26C Strong Biomarker [21]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [22]
Nasopharyngeal carcinoma DISAOTQ0 Strong Altered Expression [23]
Non-insulin dependent diabetes DISK1O5Z Strong Altered Expression [24]
Obesity DIS47Y1K Strong Biomarker [25]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [12]
Rheumatoid arthritis DISTSB4J Strong Biomarker [26]
Squamous cell carcinoma DISQVIFL Strong Posttranslational Modification [1]
Stomach cancer DISKIJSX Strong Biomarker [27]
Type-1/2 diabetes DISIUHAP Strong Altered Expression [28]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [8]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [8]
Vascular disease DISVS67S Strong Biomarker [19]
Breast carcinoma DIS2UE88 moderate Biomarker [22]
Melanoma DIS1RRCY Disputed Biomarker [29]
Neoplasm DISZKGEW Disputed Biomarker [14]
Adult glioblastoma DISVP4LU Limited Biomarker [16]
Bone osteosarcoma DIST1004 Limited Altered Expression [30]
Colitis DISAF7DD Limited Biomarker [31]
Gastric cancer DISXGOUK Limited Biomarker [27]
Gastric neoplasm DISOKN4Y Limited Biomarker [32]
Hereditary diffuse gastric adenocarcinoma DISUIBYS Limited Biomarker [32]
Non-small-cell lung cancer DIS5Y6R9 Limited Altered Expression [33]
Osteosarcoma DISLQ7E2 Limited Altered Expression [30]
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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
2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Decitabine DMQL8XJ Approved Decitabine increases the expression of Spermatogenic leucine zipper protein 1 (SPZ1). [32]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Spermatogenic leucine zipper protein 1 (SPZ1). [35]
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References

1 Differential role of gene hypermethylation in adenocarcinomas, squamous cell carcinomas and cervical intraepithelial lesions of the uterine cervix.Pathol Int. 2015 Sep;65(9):476-85. doi: 10.1111/pin.12332. Epub 2015 Jul 27.
2 Oral chromium picolinate impedes hyperglycemia-induced atherosclerosis and inhibits proatherogenic protein TSP-1 expression in STZ-induced type 1 diabetic ApoE(-/-) mice.Sci Rep. 2017 Mar 27;7:45279. doi: 10.1038/srep45279.
3 Tumoral expression of TXR1 and TSP1 predicts overall survival of patients with lung adenocarcinoma treated with first-line docetaxel-gemcitabine regimen.Clin Cancer Res. 2009 Jun 1;15(11):3827-33. doi: 10.1158/1078-0432.CCR-08-3027. Epub 2009 May 12.
4 Association of epigenetic inactivation of RASSF1A with poor outcome in human neuroblastoma.Clin Cancer Res. 2004 Dec 15;10(24):8493-500. doi: 10.1158/1078-0432.CCR-04-1331.
5 Thrombospondin-1 and -2 messenger RNA expression in epithelial ovarian tumor.Anticancer Res. 2001 Jul-Aug;21(4B):2983-7.
6 The aberrant methylation of TSP1 suppresses TGF-beta1 activation in colorectal cancer.Int J Cancer. 2008 Jul 1;123(1):14-21. doi: 10.1002/ijc.23608.
7 Thrombospondin-1 promotes tumor progression in cutaneous T-cell lymphoma via CD47.Leukemia. 2020 Mar;34(3):845-856. doi: 10.1038/s41375-019-0622-6. Epub 2019 Nov 11.
8 The Pathological Significance and Prognostic Roles of Thrombospondin-1, and -2, and 4N1K-peptide in Bladder Cancer.Anticancer Res. 2019 May;39(5):2317-2324. doi: 10.21873/anticanres.13348.
9 ADAM12 Is a Novel Regulator of Tumor Angiogenesis via STAT3 Signaling.Mol Cancer Res. 2017 Nov;15(11):1608-1622. doi: 10.1158/1541-7786.MCR-17-0188. Epub 2017 Aug 1.
10 Thrombospondins and tumor angiogenesis.Trends Mol Med. 2001 Sep;7(9):401-7. doi: 10.1016/s1471-4914(01)02102-5.
11 TIP60-dependent acetylation of the SPZ1-TWIST complex promotes epithelial-mesenchymal transition and metastasis in liver cancer.Oncogene. 2019 Jan;38(4):518-532. doi: 10.1038/s41388-018-0457-z. Epub 2018 Aug 28.
12 Transient potential receptor channel 4 controls thrombospondin-1 secretion and angiogenesis in renal cell carcinoma.FEBS J. 2007 Dec;274(24):6365-77. doi: 10.1111/j.1742-4658.2007.06159.x. Epub 2007 Nov 15.
13 15-Lipoxygenase-1 re-expression in colorectal cancer alters endothelial cell features through enhanced expression of TSP-1 and ICAM-1.Cell Signal. 2017 Nov;39:44-54. doi: 10.1016/j.cellsig.2017.07.022. Epub 2017 Jul 28.
14 AAV-mediated expression of 3TSR inhibits tumor and metastatic lesion development and extends survival in a murine model of epithelial ovarian carcinoma.Cancer Gene Ther. 2020 May;27(5):356-367. doi: 10.1038/s41417-019-0108-8. Epub 2019 Jun 4.
15 PRDX6 attenuates oxidative stress- and TGFbeta-induced abnormalities of human trabecular meshwork cells.Free Radic Res. 2009 Sep;43(9):783-95. doi: 10.1080/10715760903062887. Epub 2009 Jul 1.
16 Reverting the molecular fingerprint of tumor dormancy as a therapeutic strategy for glioblastoma.FASEB J. 2018 Jun 1:fj201701568R. doi: 10.1096/fj.201701568R. Online ahead of print.
17 Overexpression of thrombospondin-1 reduces growth and vascular index but not perfusion in glioblastoma.Cancer Res. 2002 Feb 15;62(4):1191-5.
18 Transcription factor SPZ1 promotes TWIST-mediated epithelial-mesenchymal transition and oncogenesis in human liver cancer.Oncogene. 2017 Aug;36(31):4405-4414. doi: 10.1038/onc.2017.69. Epub 2017 Apr 3.
19 Vascular TSP1-CD47 signaling promotes sickle cell-associated arterial vasculopathy and pulmonary hypertension in mice.Am J Physiol Lung Cell Mol Physiol. 2019 Jun 1;316(6):L1150-L1164. doi: 10.1152/ajplung.00302.2018. Epub 2019 Mar 20.
20 Application of transcutaneous carbon dioxide improves capillary regression of skeletal muscle in hyperglycemia.J Physiol Sci. 2019 Mar;69(2):317-326. doi: 10.1007/s12576-018-0648-y. Epub 2018 Nov 26.
21 Identification and validation of novel circulating biomarkers for early diagnosis of lung cancer.Lung Cancer. 2019 Sep;135:130-137. doi: 10.1016/j.lungcan.2019.06.019. Epub 2019 Jun 18.
22 SPZ1 is critical for chemoresistance and aggressiveness in drug-resistant breast cancer cells.Biochem Pharmacol. 2018 Oct;156:43-51. doi: 10.1016/j.bcp.2018.07.046. Epub 2018 Aug 1.
23 Anti-angiogenic pathway associations of the 3p21.3 mapped BLU gene in nasopharyngeal carcinoma.Oncogene. 2015 Aug 6;34(32):4219-28. doi: 10.1038/onc.2014.353. Epub 2014 Oct 27.
24 Compromised Neurotrophic and Angiogenic Regenerative Capability during Tendon Healing in a Rat Model of Type-II Diabetes.PLoS One. 2017 Jan 25;12(1):e0170748. doi: 10.1371/journal.pone.0170748. eCollection 2017.
25 Interaction of thrombospondin1 and CD36 contributes to obesity-associated podocytopathy.Biochim Biophys Acta. 2015 Jul;1852(7):1323-33. doi: 10.1016/j.bbadis.2015.03.010. Epub 2015 Mar 31.
26 Inhibition of angiogenesis by arsenic trioxide via TSP-1-TGF-1-CTGF-VEGF functional module in rheumatoid arthritis.Oncotarget. 2017 Aug 3;8(43):73529-73546. doi: 10.18632/oncotarget.19867. eCollection 2017 Sep 26.
27 IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK pathway.Biochem Biophys Res Commun. 2006 Jun 16;344(4):1284-9. doi: 10.1016/j.bbrc.2006.04.016. Epub 2006 Apr 21.
28 Diabetes Impairs Angiogenesis and Induces Endothelial Cell Senescence by Up-Regulating Thrombospondin-CD47-Dependent Signaling.Int J Mol Sci. 2019 Feb 4;20(3):673. doi: 10.3390/ijms20030673.
29 Matricellular TSP-1 as a target of interest for impeding melanoma spreading: towards a therapeutic use for TAX2 peptide.Clin Exp Metastasis. 2016 Oct;33(7):637-49. doi: 10.1007/s10585-016-9803-0. Epub 2016 Jun 27.
30 Thrombospondin-1 promotes cell migration, invasion and lung metastasis of osteosarcoma through FAK dependent pathway.Oncotarget. 2017 Apr 26;8(44):75881-75892. doi: 10.18632/oncotarget.17427. eCollection 2017 Sep 29.
31 Endothelial MT1-MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axis.EMBO Mol Med. 2020 Feb 7;12(2):e10862. doi: 10.15252/emmm.201910862. Epub 2019 Dec 3.
32 Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
33 Correlation of BRCA1, TXR1 and TSP1 mRNA expression with treatment outcome to docetaxel-based first-line chemotherapy in patients with advanced/metastatic non-small-cell lung cancer.Br J Cancer. 2011 Jan 18;104(2):316-23. doi: 10.1038/sj.bjc.6606027. Epub 2010 Dec 14.
34 Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
35 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.