Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX8TMVU)

• DOT Name: Golgi SNAP receptor complex member 1 (GOSR1)
• Synonyms: 28 kDa Golgi SNARE protein; 28 kDa cis-Golgi SNARE p28; GOS-28
• Gene Name: GOSR1
• Related Disease:
  B-cell neoplasm
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Autoimmune disease
  Brain neoplasm
  Carcinoma of esophagus
  Cervical cancer
  Colorectal carcinoma
  Encephalitis
  Glioma
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Multiple sclerosis
  Myocardial infarction
  Myopia
  Neoplasm
  Schizophrenia
  Breast cancer
  Breast carcinoma
  Influenza
  Melanoma
  Nervous system inflammation
• UniProt ID: GOSR1_HUMAN
• Pfam ID: PF12352
• Sequence:
  MAAGTSSYWEDLRKQARQLENELDLKLVSFSKLCTSYSHSSTRDGRRDRYSSDTTPLLNG
  SSQDRMFETMAIEIEQLLARLTGVNDKMAEYTNSAGVPSLNAALMHTLQRHRDILQDYTH
  EFHKTKANFMAIRERENLMGSVRKDIESYKSGSGVNNRRTELFLKEHDHLRNSDRLIEET
  ISIAMATKENMTSQRGMLKSIHSKMNTLANRFPAVNSLIQRINLRKRRDSLILGGVIGIC
  TILLLLYAFH
• Function: Involved in transport from the ER to the Golgi apparatus as well as in intra-Golgi transport. It belongs to a super-family of proteins called t-SNAREs or soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor. May play a protective role against hydrogen peroxide induced cytotoxicity under glutathione depleted conditions in neuronal cells by regulating the intracellular ROS levels via inhibition of p38 MAPK (MAPK11, MAPK12, MAPK13 and MAPK14). Participates in docking and fusion stage of ER to cis-Golgi transport. Plays an important physiological role in VLDL-transport vesicle-Golgi fusion and thus in VLDL delivery to the hepatic cis-Golgi.
• KEGG Pathway: S.RE interactions in vesicular transport (hsa04130)
• Reactome Pathway:
  Intra-Golgi traffic (R-HSA-6811438)
  COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[5]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[6]
Cervical cancer	DISFSHPF	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Encephalitis	DISLD1RL	Strong	Biomarker	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[5]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[10]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[4]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[13]
Myopia	DISK5S60	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[15]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[16]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[16]
Influenza	DIS3PNU3	moderate	Altered Expression	[17]
Melanoma	DIS1RRCY	moderate	Altered Expression	[16]
Nervous system inflammation	DISB3X5A	Limited	Altered Expression	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Nitric Oxide	DM1RBYG	Approved	Golgi SNAP receptor complex member 1 (GOSR1) increases the Apoptosis ADR of Nitric Oxide.	[27]

8 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 Golgi SNAP receptor complex member 1 (GOSR1).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Golgi SNAP receptor complex member 1 (GOSR1).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Golgi SNAP receptor complex member 1 (GOSR1).	[21]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Golgi SNAP receptor complex member 1 (GOSR1).	[22]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Golgi SNAP receptor complex member 1 (GOSR1).	[23]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Golgi SNAP receptor complex member 1 (GOSR1).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Golgi SNAP receptor complex member 1 (GOSR1).	[24]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Golgi SNAP receptor complex member 1 (GOSR1).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Golgi SNAP receptor complex member 1 (GOSR1).	[26]

References

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• [17] Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity.Front Microbiol. 2019 Mar 6;10:432. doi: 10.3389/fmicb.2019.00432. eCollection 2019.
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• [22] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
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