Details of Drug Off-Target (DOT)

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

• DOT Name: Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1)
• Synonyms: Csk-binding protein; Transmembrane adapter protein PAG; Transmembrane phosphoprotein Cbp
• Gene Name: PAG1
• Related Disease:
  Bone osteosarcoma
  Intellectual disability
  leukaemia
  Osteosarcoma
  Rheumatoid arthritis
  Rubinstein-Taybi syndrome
  Acute leukaemia
  Acute lymphocytic leukaemia
  Acute myelomonocytic leukemia M4
  Advanced cancer
  Alzheimer disease
  Bladder cancer
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  Huntington disease
  Leukemia
  Lung cancer
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
  Squamous cell carcinoma
  Status epilepticus seizure
  Thyroid gland papillary carcinoma
  Type-1/2 diabetes
  Ulcerative colitis
  Urinary bladder cancer
  Urinary bladder neoplasm
  High blood pressure
  Lung adenocarcinoma
  Lung carcinoma
  Lymphoma
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Childhood acute lymphoblastic leukemia
  Gastric cancer
  Laryngeal carcinoma
  Melanoma
  Neuroblastoma
  Non-small-cell lung cancer
  Rett syndrome
  Rothmund-Thomson syndrome
  Stomach cancer
• UniProt ID: PHAG1_HUMAN
• Pfam ID: PF15347
• Sequence:
  MGPAGSLLGSGQMQITLWGSLAAVAIFFVITFLIFLCSSCDREKKPRQHSGDHENLMNVP
  SDKEMFSRSVTSLATDAPASSEQNGALTNGDILSEDSTLTCMQHYEEVQTSASDLLDSQD
  STGKPKCHQSRELPRIPPESAVDTMLTARSVDGDQGLGMEGPYEVLKDSSSQENMVEDCL
  YETVKEIKEVAAAAHLEKGHSGKAKSTSASKELPGPQTEGKAEFAEYASVDRNKKCRQSV
  NVESILGNSCDPEEEAPPPVPVKLLDENENLQEKEGGEAEESATDTTSETNKRFSSLSYK
  SREEDPTLTEEEISAMYSSVNKPGQLVNKSGQSLTVPESTYTSIQGDPQRSPSSCNDLYA
  TVKDFEKTPNSTLPPAGRPSEEPEPDYEAIQTLNREEEKATLGTNGHHGLVPKENDYESI
  SDLQQGRDITRL
• Function: Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Promotes CSK activation and recruitment to lipid rafts, which results in LCK inhibition. Inhibits immunological synapse formation by preventing dynamic arrangement of lipid raft proteins. May be involved in cell adhesion signaling.
• Tissue Specificity: Ubiquitously expressed. Present in germinal center B-cells, plasma cells, T-cells, monocytes and platelets (at protein level).
• Reactome Pathway:
  Phosphorylation of CD3 and TCR zeta chains (R-HSA-202427)
  GAB1 signalosome (R-HSA-180292)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Biomarker	[1]
Intellectual disability	DISMBNXP	Definitive	Genetic Variation	[2]
leukaemia	DISS7D1V	Definitive	Genetic Variation	[3]
Osteosarcoma	DISLQ7E2	Definitive	Biomarker	[1]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[4]
Rubinstein-Taybi syndrome	DISVF1HM	Definitive	Biomarker	[5]
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[6]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[7]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Genetic Variation	[8]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[9]
Alzheimer disease	DISF8S70	Strong	Biomarker	[10]
Bladder cancer	DISUHNM0	Strong	Biomarker	[11]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[12]
Colon cancer	DISVC52G	Strong	Biomarker	[13]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[14]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
Huntington disease	DISQPLA4	Strong	Altered Expression	[17]
Leukemia	DISNAKFL	Strong	Genetic Variation	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Neoplasm	DISZKGEW	Strong	Altered Expression	[19]
Prostate cancer	DISF190Y	Strong	Biomarker	[20]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[20]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[21]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[22]
Status epilepticus seizure	DISY3BIC	Strong	Altered Expression	[23]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Biomarker	[24]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[25]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[26]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[11]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[11]
High blood pressure	DISY2OHH	moderate	Biomarker	[27]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[28]
Lung carcinoma	DISTR26C	moderate	Biomarker	[18]
Lymphoma	DISN6V4S	moderate	Biomarker	[29]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[30]
Breast cancer	DIS7DPX1	Limited	Biomarker	[31]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[31]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Altered Expression	[3]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[32]
Laryngeal carcinoma	DISNHCIV	Limited	Biomarker	[33]
Melanoma	DIS1RRCY	Limited	Biomarker	[34]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[35]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[36]
Rett syndrome	DISGG5UV	Limited	Biomarker	[37]
Rothmund-Thomson syndrome	DISGVBCV	Limited	Biomarker	[37]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[38]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[53]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[41]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[43]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[45]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[46]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[47]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[48]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[49]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[50]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[51]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[52]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[54]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[52]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[55]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[56]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[57]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[58]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[59]
Taurine	DMVW7N3	Investigative	Taurine decreases the expression of Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1).	[60]

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