Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWFV4KA)

• DOT Name: Synaptonemal complex protein 1 (SYCP1)
• Synonyms: SCP-1; Cancer/testis antigen 8; CT8
• Gene Name: SYCP1
• Related Disease:
  Breast carcinoma
  Acute myelogenous leukaemia
  Adenocarcinoma
  Chronic pancreatitis
  Clear cell renal carcinoma
  Hyperglycemia
  Liver cancer
  Pancreatic cancer
  Pancreatic tumour
  Plasma cell myeloma
  Precancerous condition
  Primary cutaneous T-cell lymphoma
  Progressive multifocal leukoencephalopathy
  Synovial sarcoma
  Xeroderma pigmentosum
  Testicular cancer
  Helicoid peripapillary chorioretinal degeneration
• UniProt ID: SYCP1_HUMAN
• PDB ID: 4YTO; 6F5X; 6F62; 6F63; 6F64
• Pfam ID: PF05483
• Sequence:
  MEKQKPFALFVPPRSSSSQVSAVKPQTLGGDSTFFKSFNKCTEDDFEFPFAKTNLSKNGE
  NIDSDPALQKVNFLPVLEQVGNSDCHYQEGLKDSDLENSEGLSRVYSKLYKEAEKIKKWK
  VSTEAELRQKESKLQENRKIIEAQRKAIQELQFGNEKVSLKLEEGIQENKDLIKENNATR
  HLCNLLKETCARSAEKTKKYEYEREETRQVYMDLNNNIEKMITAFEELRVQAENSRLEMH
  FKLKEDYEKIQHLEQEYKKEINDKEKQVSLLLIQITEKENKMKDLTFLLEESRDKVNQLE
  EKTKLQSENLKQSIEKQHHLTKELEDIKVSLQRSVSTQKALEEDLQIATKTICQLTEEKE
  TQMEESNKARAAHSFVVTEFETTVCSLEELLRTEQQRLEKNEDQLKILTMELQKKSSELE
  EMTKLTNNKEVELEELKKVLGEKETLLYENKQFEKIAEELKGTEQELIGLLQAREKEVHD
  LEIQLTAITTSEQYYSKEVKDLKTELENEKLKNTELTSHCNKLSLENKELTQETSDMTLE
  LKNQQEDINNNKKQEERMLKQIENLQETETQLRNELEYVREELKQKRDEVKCKLDKSEEN
  CNNLRKQVENKNKYIEELQQENKALKKKGTAESKQLNVYEIKVNKLELELESAKQKFGEI
  TDTYQKEIEDKKISEENLLEEVEKAKVIADEAVKLQKEIDKRCQHKIAEMVALMEKHKHQ
  YDKIIEERDSELGLYKSKEQEQSSLRASLEIELSNLKAELLSVKKQLEIEREEKEKLKRE
  AKENTATLKEKKDKKTQTFLLETPEIYWKLDSKAVPSQTVSRNFTSVDHGISKDKRDYLW
  TSAKNTLSTPLPKAYTVKTPTKPKLQQRENLNIPIEESKKKRKMAFEFDINSDSSETTDL
  LSMVSEEETLKTLYRNNNPPASHLCVKTPKKAPSSLTTPGSTLKFGAIRKMREDRWAVIA
  KMDRKKKLKEAEKLFV
• Function: Major component of the transverse filaments of synaptonemal complexes, formed between homologous chromosomes during meiotic prophase. Required for normal assembly of the central element of the synaptonemal complexes. Required for normal centromere pairing during meiosis. Required for normal meiotic chromosome synapsis during oocyte and spermatocyte development and for normal male and female fertility.
• Tissue Specificity: Testis.
• Reactome Pathway: Meiotic synapsis (R-HSA-1221632)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[3]
Chronic pancreatitis	DISBUOMJ	Strong	Altered Expression	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[4]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[5]
Liver cancer	DISDE4BI	Strong	Biomarker	[6]
Pancreatic cancer	DISJC981	Strong	Biomarker	[3]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[3]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[2]
Precancerous condition	DISV06FL	Strong	Biomarker	[3]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Biomarker	[7]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[4]
Synovial sarcoma	DISEZJS7	Strong	Genetic Variation	[8]
Xeroderma pigmentosum	DISQ9H19	Strong	Genetic Variation	[8]
Testicular cancer	DIS6HNYO	moderate	Altered Expression	[9]
Helicoid peripapillary chorioretinal degeneration	DISFSS5N	Limited	Genetic Variation	[10]

3 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 Synaptonemal complex protein 1 (SYCP1).	[11]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Synaptonemal complex protein 1 (SYCP1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Synaptonemal complex protein 1 (SYCP1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Synaptonemal complex protein 1 (SYCP1).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Synaptonemal complex protein 1 (SYCP1).	[14]
Flavone	DMEQH6J	Investigative	Flavone increases the expression of Synaptonemal complex protein 1 (SYCP1).	[16]

References

• [1] Breast carcinoma cells modulate the chemoattractive activity of human bone marrow-derived mesenchymal stromal cells by interfering with CXCL12.Int J Cancer. 2015 Jan 1;136(1):44-54. doi: 10.1002/ijc.28960. Epub 2014 May 20.
• [2] Expression of testicular genes in haematological malignancies.Br J Cancer. 1999 Dec;81(7):1162-4. doi: 10.1038/sj.bjc.6690824.
• [3] Expression of cancer testis antigens in pancreatic carcinoma cell lines, pancreatic adenocarcinoma and chronic pancreatitis.Int J Cancer. 2004 Apr 20;109(4):568-75. doi: 10.1002/ijc.20006.
• [4] SCP phosphatases suppress renal cell carcinoma by stabilizing PML and inhibiting mTOR/HIF signaling.Cancer Res. 2014 Dec 1;74(23):6935-46. doi: 10.1158/0008-5472.CAN-14-1330. Epub 2014 Oct 7.
• [5] Physicochemical properties of polysaccharides separated from Camellia oleifera Abel seed cake and its hypoglycemic activity on streptozotocin-induced diabetic mice.Int J Biol Macromol. 2019 Mar 15;125:1075-1083. doi: 10.1016/j.ijbiomac.2018.12.059. Epub 2018 Dec 5.
• [6] SCP1 regulates c-Myc stability and functions through dephosphorylating c-Myc Ser62.Oncogene. 2016 Jan 28;35(4):491-500. doi: 10.1038/onc.2015.106. Epub 2015 Apr 20.
• [7] Expression of cancer/testis antigens in cutaneous T cell lymphomas.Int J Cancer. 2002 Feb 10;97(5):668-70. doi: 10.1002/ijc.1643.
• [8] Reactivity of germ cell maturation stage-specific markers in spermatocytic seminoma: diagnostic and etiological implications.Lab Invest. 2001 Jul;81(7):919-28. doi: 10.1038/labinvest.3780302.
• [9] Prospective study on the expression of cancer testis genes and antibody responses in 100 consecutive patients with primary breast cancer.Int J Cancer. 2006 Feb 1;118(3):696-703. doi: 10.1002/ijc.21352.
• [10] Cloning and characterization of the first serine carboxypeptidase from a plant parasitic nematode, Radopholus similis.Sci Rep. 2017 Jul 6;7(1):4815. doi: 10.1038/s41598-017-05093-7.
• [11] 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.
• [12] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [13] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [14] The DNA demethylating agent 5-aza-2'-deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma. Int J Cancer. 2008 Jun 1;122(11):2542-53. doi: 10.1002/ijc.23407.
• [15] 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.
• [16] Identification of biomarkers for the initiation of apoptosis in human preneoplastic colonocytes by proteome analysis. Int J Cancer. 2004 Mar 20;109(2):220-9. doi: 10.1002/ijc.11692.