Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6Z4BPQ)

• DOT Name: Semenogelin-1 (SEMG1)
• Synonyms: Cancer/testis antigen 103; Semenogelin I; SGI
• Gene Name: SEMG1
• Related Disease:
  Myelodysplastic syndrome
  Advanced cancer
  Amyloidosis
  Carpal tunnel syndrome
  Childhood myelodysplastic syndrome
  Clear cell renal carcinoma
  leukaemia
  Leukemia
  Lymphoma, non-Hodgkin, familial
  Matthew-Wood syndrome
  Neoplasm
  Non-hodgkin lymphoma
  Oligospermia
  Ovarian cancer
  Ovarian neoplasm
  Plasma cell myeloma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Small lymphocytic lymphoma
  Triple negative breast cancer
  Acute myelogenous leukaemia
  Bladder cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Colorectal carcinoma
  Colorectal neoplasm
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Mood disorder
  Psychotic disorder
  Testicular cancer
• UniProt ID: SEMG1_HUMAN
• PDB ID: 7ZRF; 7ZRO; 8BOO; 8BVZ
• Pfam ID: PF05474
• Sequence:
  MKPNIIFVLSLLLILEKQAAVMGQKGGSKGRLPSEFSQFPHGQKGQHYSGQKGKQQTESK
  GSFSIQYTYHVDANDHDQSRKSQQYDLNALHKTTKSQRHLGGSQQLLHNKQEGRDHDKSK
  GHFHRVVIHHKGGKAHRGTQNPSQDQGNSPSGKGISSQYSNTEERLWVHGLSKEQTSVSG
  AQKGRKQGGSQSSYVLQTEELVANKQQRETKNSHQNKGHYQNVVEVREEHSSKVQTSLCP
  AHQDKLQHGSKDIFSTQDELLVYNKNQHQTKNLNQDQQHGRKANKISYQSSSTEERRLHY
  GENGVQKDVSQSSIYSQTEEKAQGKSQKQITIPSQEQEHSQKANKISYQSSSTEERRLHY
  GENGVQKDVSQRSIYSQTEKLVAGKSQIQAPNPKQEPWHGENAKGESGQSTNREQDLLSH
  EQKGRHQHGSHGGLDIVIIEQEDDSDRHLAQHLNNDRNPLFT
• Function: Predominant protein in semen. It participates in the formation of a gel matrix entrapping the accessory gland secretions and ejaculated spermatozoa. Fragments of semenogelin and/or fragments of the related proteins may contribute to the activation of progressive sperm movements as the gel-forming proteins are fragmented by KLK3/PSA; Alpha-inhibin-92 and alpha-inhibin-31, derived from the proteolytic degradation of semenogelin, inhibit the secretion of pituitary follicle-stimulating hormone.
• Tissue Specificity: Seminal vesicle.
• Reactome Pathway:
  Amyloid fiber formation (R-HSA-977225)
  Antimicrobial peptides (R-HSA-6803157)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myelodysplastic syndrome	DISYHNUI	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Amyloidosis	DISHTAI2	Strong	Biomarker	[3]
Carpal tunnel syndrome	DISHQ3BE	Strong	Biomarker	[4]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[5]
leukaemia	DISS7D1V	Strong	Biomarker	[6]
Leukemia	DISNAKFL	Strong	Biomarker	[6]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[7]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[7]
Oligospermia	DIS6YJF3	Strong	Genetic Variation	[10]
Ovarian cancer	DISZJHAP	Strong	Posttranslational Modification	[11]
Ovarian neoplasm	DISEAFTY	Strong	Posttranslational Modification	[11]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[12]
Prostate cancer	DISF190Y	Strong	Biomarker	[13]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[13]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[5]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[14]
Triple negative breast cancer	DISAMG6N	Strong	Genetic Variation	[15]
Acute myelogenous leukaemia	DISCSPTN	moderate	Biomarker	[1]
Bladder cancer	DISUHNM0	moderate	Genetic Variation	[2]
Urinary bladder cancer	DISDV4T7	moderate	Genetic Variation	[2]
Urinary bladder neoplasm	DIS7HACE	moderate	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[16]
Colorectal neoplasm	DISR1UCN	Limited	Genetic Variation	[16]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[17]
Mood disorder	DISLVMWO	Limited	Biomarker	[18]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[18]
Testicular cancer	DIS6HNYO	Limited	Altered Expression	[9]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Semenogelin-1 (SEMG1) affects the response to substance of Methotrexate.	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Semenogelin-1 (SEMG1).	[19]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Semenogelin-1 (SEMG1).	[20]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Semenogelin-1 (SEMG1).	[21]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Semenogelin-1 (SEMG1).	[23]

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 Semenogelin-1 (SEMG1).	[22]

References

• [1] Guadecitabine (SGI-110): an investigational drug for the treatment of myelodysplastic syndrome and acute myeloid leukemia.Expert Opin Investig Drugs. 2019 Oct;28(10):835-849. doi: 10.1080/13543784.2019.1667331. Epub 2019 Sep 19.
• [2] SPIRE - combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial.Trials. 2018 Apr 3;19(1):216. doi: 10.1186/s13063-018-2586-7.
• [3] Seminal Tract Amyloidosis: Synchronous Amyloidosis of the Seminal Vesicles, Deferent Ducts and Ejaculatory Ducts.Pathol Oncol Res. 2017 Oct;23(4):811-814. doi: 10.1007/s12253-017-0193-7. Epub 2017 Jan 17.
• [4] Motor unit number index (MUNIX) derivation from the relationship between the area and power of surface electromyogram: a computer simulation and clinical study.J Neural Eng. 2018 Jun;15(3):036013. doi: 10.1088/1741-2552/aaae19. Epub 2018 Feb 9.
• [5] Seminal plasma protein in renal cell carcinoma: expression of semenogelin I is a predictor for cancer progression and prognosis.Tumour Biol. 2014 Sep;35(9):9095-100. doi: 10.1007/s13277-014-2184-6. Epub 2014 Jun 11.
• [6] Transcription and translation are primary targets of Pim kinase inhibitor SGI-1776 in mantle cell lymphoma.Blood. 2012 Oct 25;120(17):3491-500. doi: 10.1182/blood-2012-02-412643. Epub 2012 Sep 6.
• [7] Retrospective identification of a previously undetected clinical case of OXA-48-producing K. pneumoniae and E. coli: the importance of adequate detection guidelines.Infection. 2016 Feb;44(1):107-10. doi: 10.1007/s15010-015-0805-7. Epub 2015 Jun 11.
• [8] A novel epigenetic modulating agent sensitizes pancreatic cells to a chemotherapy agent.PLoS One. 2018 Jun 21;13(6):e0199130. doi: 10.1371/journal.pone.0199130. eCollection 2018.
• [9] Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts. Epigenetics. 2015;10(3):237-46.
• [10] Sequence variation at KLK and WFDC clusters and its association to semen hyperviscosity and other male infertility phenotypes.Hum Reprod. 2016 Dec;31(12):2881-2891. doi: 10.1093/humrep/dew267. Epub 2016 Nov 7.
• [11] The novel, small-molecule DNA methylation inhibitor SGI-110 as an ovarian cancer chemosensitizer.Clin Cancer Res. 2014 Dec 15;20(24):6504-16. doi: 10.1158/1078-0432.CCR-14-1553. Epub 2014 Oct 14.
• [12] Pattern of gene expression and immune responses to Semenogelin 1 in chronic hematologic malignancies.J Immunother. 2003 Nov-Dec;26(6):461-7. doi: 10.1097/00002371-200311000-00001.
• [13] The interaction between androgen receptor and semenogelin I: a synthetic LxxLL peptide antagonist inhibits the growth of prostate cancer cells.Br J Cancer. 2018 Feb 6;118(3):416-420. doi: 10.1038/bjc.2017.404. Epub 2017 Nov 14.
• [14] SEMG-1 expression in early stage chronic lymphocytic leukemia.Cytotherapy. 2009;11(2):238-44. doi: 10.1080/14653240802716608.
• [15] Epigenetic reprogramming of epithelial mesenchymal transition in triple negative breast cancer cells with DNA methyltransferase and histone deacetylase inhibitors.J Exp Clin Cancer Res. 2018 Dec 14;37(1):314. doi: 10.1186/s13046-018-0988-8.
• [16] Mutations in two short noncoding mononucleotide repeats in most microsatellite-unstable colorectal cancers.Cancer Res. 2005 Jun 1;65(11):4607-13. doi: 10.1158/0008-5472.CAN-05-0165.
• [17] Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor Guadecitabine (SGI-110) in Hepatocellular Carcinoma.Hepatology. 2018 Oct;68(4):1412-1428. doi: 10.1002/hep.30091.
• [18] Mood disorders in first- and second-generation immigrants: systematic review and meta-analysis.Br J Psychiatry. 2017 Mar;210(3):182-189. doi: 10.1192/bjp.bp.116.181107. Epub 2017 Jan 9.
• [19] 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.
• [20] Semenogelin I expression in myeloma cells can be upregulated pharmacologically. Leuk Res. 2008 Dec;32(12):1889-94. doi: 10.1016/j.leukres.2008.03.036. Epub 2008 May 12.
• [21] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [22] 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.
• [23] Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture. Chem Res Toxicol. 2009 Jun;22(6):1077-85.
• [24] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.