Details of Drug Off-Target (DOT)

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

• DOT Name: Synaptotagmin-like protein 2 (SYTL2)
• Synonyms: Breast cancer-associated antigen SGA-72M; Exophilin-4
• Gene Name: SYTL2
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Advanced cancer
  Benign neoplasm
  Carcinoma of esophagus
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Cystic fibrosis
  Epithelial ovarian cancer
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Squamous cell carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  Limb-girdle muscular dystrophy
  Stomach cancer
  Thyroid gland papillary carcinoma
  Adenoma
  Endometrium adenocarcinoma
  Gallbladder cancer
  Gallbladder carcinoma
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: SYTL2_HUMAN
• PDB ID: 3BC1; 7OPP; 7OPQ; 7OPR
• Pfam ID: PF00168 ; PF02318
• Sequence:
  MIDLSFLTEEEQEAIMKVLQRDAALKRAEEERVRHLPEKIKDDQQLKNMSGQWFYEAKAK
  RHRDKIHGADIIRASMRKKRPQIAAEQSKDRENGAKESWVNNVNKDAFLPPELAGVVEEP
  EEDAAPASPSSSVVNPASSVIDMSQENTRKPNVSPEKRKNPFNSSKLPEGHSSQQTKNEQ
  SKNGRTGLFQTSKEDELSESKEKSTVADTSIQKLEKSKQTLPGLSNGSQIKAPIPKARKM
  IYKSTDLNKDDNQSFPRQRTDSLKARGAPRGILKRNSSSSSTDSETLRYNHNFEPKSKIV
  SPGLTIHERISEKEHSLEDNSSPNSLEPLKHVRFSAVKDELPQSPGLIHGREVGEFSVLE
  SDRLKNGMEDAGDTEEFQSDPKPSQYRKPSLFHQSTSSPYVSKSETHQPMTSGSFPINGL
  HSHSEVLTARPQSMENSPTINEPKDKSSELTRLESVLPRSPADELSHCVEPEPSQVPGGS
  SRDRQQGSEEEPSPVLKTLERSAARKMPSKSLEDISSDSSNQAKVDNQPEELVRSAEDVS
  TVPTQPDNPFSHPDKLKRMSKSVPAFLQDESDDRETDTASESSYQLSRHKKSPSSLTNLS
  SSSGMTSLSSVSGSVMSVYSGDFGNLEVKGNIQFAIEYVESLKELHVFVAQCKDLAAADV
  KKQRSDPYVKAYLLPDKGKMGKKKTLVVKKTLNPVYNEILRYKIEKQILKTQKLNLSIWH
  RDTFKRNSFLGEVELDLETWDWDNKQNKQLRWYPLKRKTAPVALEAENRGEMKLALQYVP
  EPVPGKKLPTTGEVHIWVKECLDLPLLRGSHLNSFVKCTILPDTSRKSRQKTRAVGKTTN
  PIFNHTMVYDGFRPEDLMEACVELTVWDHYKLTNQFLGGLRIGFGTGKSYGTEVDWMDST
  SEEVALWEKMVNSPNTWIEATLPLRMLLIAKISK
• Function: Isoform 1 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. It is required for cytotoxic granule docking at the immunologic synapse. Isoform 4 binds phosphatidylserine (PS) and phosphatidylinositol-4,5-bisphosphate (PIP2) and promotes the recruitment of glucagon-containing granules to the cell membrane in pancreatic alpha cells. Binding to PS is inhibited by Ca(2+) while binding to PIP2 is Ca(2+) insensitive.
• Tissue Specificity: Isoform 1 is expressed in hematopoietic lineages with a strong expression in CD4 and CD8 T-lymphocytes. It is also widely expressed in nonhematopoietic tissues. Isoform 5 is expressed only in nonhematopoietic tissues. Isoform 4 is expressed in pancreatic alpha cells.

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Biomarker	[1]
Liver cancer	DISDE4BI	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Benign neoplasm	DISDUXAD	Strong	Altered Expression	[3]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[4]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[2]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[6]
Lung cancer	DISCM4YA	Strong	Altered Expression	[7]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[4]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[9]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[7]
Gastric cancer	DISXGOUK	moderate	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[11]
Limb-girdle muscular dystrophy	DISI9Y1Z	moderate	Altered Expression	[12]
Stomach cancer	DISKIJSX	moderate	Biomarker	[10]
Thyroid gland papillary carcinoma	DIS48YMM	moderate	Biomarker	[13]
Adenoma	DIS78ZEV	Limited	Altered Expression	[14]
Endometrium adenocarcinoma	DISY6744	Limited	Altered Expression	[15]
Gallbladder cancer	DISXJUAF	Limited	Altered Expression	[4]
Gallbladder carcinoma	DISD6ACL	Limited	Altered Expression	[4]
Thyroid cancer	DIS3VLDH	Limited	Altered Expression	[14]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[14]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Synaptotagmin-like protein 2 (SYTL2) affects the response to substance of Mitoxantrone.	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Synaptotagmin-like protein 2 (SYTL2).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Synaptotagmin-like protein 2 (SYTL2).	[19]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[21]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Synaptotagmin-like protein 2 (SYTL2).	[22]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[23]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Synaptotagmin-like protein 2 (SYTL2).	[24]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[25]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Synaptotagmin-like protein 2 (SYTL2).	[26]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Synaptotagmin-like protein 2 (SYTL2).	[28]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[29]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[32]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[33]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Synaptotagmin-like protein 2 (SYTL2).	[34]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Synaptotagmin-like protein 2 (SYTL2).	[27]

References

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• [24] 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.
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• [33] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
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