Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVTPOI6)

• DOT Name: Synaptotagmin-1 (SYT1)
• Synonyms: Synaptotagmin I; SytI; p65
• Gene Name: SYT1
• Related Disease:
  Lung adenocarcinoma
  Melanoma
  Acute myelogenous leukaemia
  Adenocarcinoma
  Adult T-cell leukemia/lymphoma
  Alzheimer disease
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Hyperglycemia
  Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome
  Intellectual disability
  Intellectual disability, autosomal dominant 40
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Multiple sclerosis
  Non-small-cell lung cancer
  Osteoarthritis
  Osteosarcoma
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  Stomach cancer
  Systemic lupus erythematosus
  T-cell leukaemia
  Thyroid cancer
  Ulcerative colitis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Glioblastoma multiforme
  Squamous cell carcinoma
  Thyroid gland carcinoma
  Adult glioblastoma
  B-cell neoplasm
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Leukemia
  Nasopharyngeal carcinoma
• UniProt ID: SYT1_HUMAN
• PDB ID: 2K45; 2K4A; 2K8M; 2KI6; 2LHA; 2N1T; 2R83; 3F00; 3F01; 3F04; 3F05; 4ISQ; 4V11; 6G5F; 6G5K; 6QNS; 6TZ3; 6U41; 6U4U; 6U4W; 6ZVN; 7U4Q
• Pfam ID: PF00168
• Sequence:
  MVSESHHEALAAPPVTTVATVLPSNATEPASPGEGKEDAFSKLKEKFMNELHKIPLPPWA
  LIAIAIVAVLLVLTCCFCICKKCLFKKKNKKKGKEKGGKNAINMKDVKDLGKTMKDQALK
  DDDAETGLTDGEEKEEPKEEEKLGKLQYSLDYDFQNNQLLVGIIQAAELPALDMGGTSDP
  YVKVFLLPDKKKKFETKVHRKTLNPVFNEQFTFKVPYSELGGKTLVMAVYDFDRFSKHDI
  IGEFKVPMNTVDFGHVTEEWRDLQSAEKEEQEKLGDICFSLRYVPTAGKLTVVILEAKNL
  KKMDVGGLSDPYVKIHLMQNGKRLKKKKTTIKKNTLNPYYNESFSFEVPFEQIQKVQVVV
  TVLDYDKIGKNDAIGKVFVGYNSTGAELRHWSDMLANPRRPIAQWHTLQVEEEVDAMLAV
  KK
• Function: Calcium sensor that participates in triggering neurotransmitter release at the synapse. May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2. Plays a role in dendrite formation by melanocytes.
• Tissue Specificity: Expressed in melanocytes .
• KEGG Pathway: Sy.ptic vesicle cycle (hsa04721)
• Reactome Pathway:
  Norepinephrine Neurotransmitter Release Cycle (R-HSA-181430)
  Glutamate Neurotransmitter Release Cycle (R-HSA-210500)
  Dopamine Neurotransmitter Release Cycle (R-HSA-212676)
  Acetylcholine Neurotransmitter Release Cycle (R-HSA-264642)
  Toxicity of botulinum toxin type B (botB) (R-HSA-5250958)
  Toxicity of botulinum toxin type G (botG) (R-HSA-5250989)
  Neurexins and neuroligins (R-HSA-6794361)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  GABA synthesis, release, reuptake and degradation (R-HSA-888590)
  Serotonin Neurotransmitter Release Cycle (R-HSA-181429)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[11]
Gastric cancer	DISXGOUK	Strong	Biomarker	[12]
Glioma	DIS5RPEH	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[15]
Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome	DISCXG56	Strong	Autosomal dominant	[16]
Intellectual disability	DISMBNXP	Strong	Biomarker	[17]
Intellectual disability, autosomal dominant 40	DISAI0IH	Strong	Autosomal dominant	[17]
Lung cancer	DISCM4YA	Strong	Altered Expression	[18]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[19]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[21]
Osteoarthritis	DIS05URM	Strong	Biomarker	[22]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[7]
Prostate cancer	DISF190Y	Strong	Biomarker	[23]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[23]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[24]
Stomach cancer	DISKIJSX	Strong	Biomarker	[12]
Systemic lupus erythematosus	DISI1SZ7	Strong	Posttranslational Modification	[25]
T-cell leukaemia	DISJ6YIF	Strong	Altered Expression	[5]
Thyroid cancer	DIS3VLDH	Strong	Posttranslational Modification	[26]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[27]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[28]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[28]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[29]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[30]
Thyroid gland carcinoma	DISMNGZ0	moderate	Posttranslational Modification	[26]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[31]
B-cell neoplasm	DISVY326	Limited	Altered Expression	[32]
Cervical cancer	DISFSHPF	Limited	Biomarker	[33]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[33]
Colon cancer	DISVC52G	Limited	Altered Expression	[34]
Colon carcinoma	DISJYKUO	Limited	Altered Expression	[34]
Leukemia	DISNAKFL	Limited	Posttranslational Modification	[35]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Synaptotagmin-1 (SYT1).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Synaptotagmin-1 (SYT1).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Synaptotagmin-1 (SYT1).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Synaptotagmin-1 (SYT1).	[40]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Synaptotagmin-1 (SYT1).	[41]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synaptotagmin-1 (SYT1).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Synaptotagmin-1 (SYT1).	[43]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Synaptotagmin-1 (SYT1).	[44]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Synaptotagmin-1 (SYT1).	[45]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Synaptotagmin-1 (SYT1).	[46]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Synaptotagmin-1 (SYT1).	[47]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Synaptotagmin-1 (SYT1).	[48]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine decreases the expression of Synaptotagmin-1 (SYT1).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Synaptotagmin-1 (SYT1).	[51]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Synaptotagmin-1 (SYT1).	[52]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Synaptotagmin-1 (SYT1).	[53]

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 Synaptotagmin-1 (SYT1).	[50]

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