Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2Q677P)

• DOT Name: Synaptojanin-2-binding protein (SYNJ2BP)
• Synonyms: Mitochondrial outer membrane protein 25
• Gene Name: SYNJ2BP
• Related Disease:
  Advanced cancer
  Breast neoplasm
  Brucellosis
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Breast cancer
  Breast carcinoma
• UniProt ID: SYJ2B_HUMAN
• PDB ID: 2ENO; 2JIK; 2JIN; 7P73; 7P74; 7PC9; 7R2M; 7R2T; 8AEL
• Pfam ID: PF00595
• Sequence:
  MNGRVDYLVTEEEINLTRGPSGLGFNIVGGTDQQYVSNDSGIYVSRIKENGAAALDGRLQ
  EGDKILSVNGQDLKNLLHQDAVDLFRNAGYAVSLRVQHRLQVQNGPIGHRGEGDPSGIPI
  FMVLVPVFALTMVAAWAFMRYRQQL
• Function: Regulates endocytosis of activin type 2 receptor kinases through the Ral/RALBP1-dependent pathway and may be involved in suppression of activin-induced signal transduction.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Brucellosis	DISEAYGH	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Limited	Biomarker	[2]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Synaptojanin-2-binding protein (SYNJ2BP).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Synaptojanin-2-binding protein (SYNJ2BP).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Synaptojanin-2-binding protein (SYNJ2BP).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Synaptojanin-2-binding protein (SYNJ2BP).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Synaptojanin-2-binding protein (SYNJ2BP).	[9]

References

• [1] SYNJ2BP inhibits tumor growth and metastasis by activating DLL4 pathway in hepatocellular carcinoma.J Exp Clin Cancer Res. 2016 Jul 20;35(1):115. doi: 10.1186/s13046-016-0385-0.
• [2] SYNJ2BP promotes the degradation of PTEN through the lysosome-pathway and enhances breast tumor metastasis via PI3K/AKT/SNAI1 signaling.Oncotarget. 2017 Sep 19;8(52):89692-89706. doi: 10.18632/oncotarget.21058. eCollection 2017 Oct 27.
• [3] Integrative Bioinformatics Indentification of the Autophagic Pathway-Associated miRNA-mRNA Networks in RAW264.7 Macrophage Cells Infected with Omp25 Brucella melitensis.Inflammation. 2020 Apr;43(2):532-539. doi: 10.1007/s10753-019-01135-6.
• [4] A Novel Clinical Six-Flavoprotein-Gene Signature Predicts Prognosis in Esophageal Squamous Cell Carcinoma.Biomed Res Int. 2019 Oct 30;2019:3869825. doi: 10.1155/2019/3869825. eCollection 2019.
• [5] 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.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.