Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI8ZKC4)

• DOT Name: Arf-GAP domain and FG repeat-containing protein 1 (AGFG1)
• Synonyms: HIV-1 Rev-binding protein; Nucleoporin-like protein RIP; Rev-interacting protein; Rev/Rex activation domain-binding protein
• Gene Name: AGFG1
• Related Disease:
  Hepatocellular carcinoma
  Melanoma
  Advanced cancer
  Autism spectrum disorder
  Bladder cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Choroideremia
  Colitis
  Estrogen-receptor positive breast cancer
  Gastric cancer
  Glioma
  Hepatitis C virus infection
  Herpes simplex infection
  High blood pressure
  Intellectual disability
  Myopathy
  Nervous system disease
  Non-small-cell lung cancer
  Osteosarcoma
  Pancreatic cancer
  Pancreatic tumour
  Parkinson disease
  Prostate cancer
  Prostate carcinoma
  Small lymphocytic lymphoma
  Stomach cancer
  Systemic lupus erythematosus
  Type-1/2 diabetes
  Ulcerative colitis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Metastatic malignant neoplasm
  Neoplasm
  Cognitive impairment
  Amyotrophic lateral sclerosis
  Carcinoma of liver and intrahepatic biliary tract
  Clear cell renal carcinoma
  Congenital contractural arachnodactyly
  Hyperglycemia
  Liver cancer
  Nasopharyngeal carcinoma
  Plasma cell myeloma
  Renal cell carcinoma
• UniProt ID: AGFG1_HUMAN
• PDB ID: 2D9L; 2OLM; 2VX8
• Pfam ID: PF01412
• Sequence:
  MAASAKRKQEEKHLKMLRDMTGLPHNRKCFDCDQRGPTYVNMTVGSFVCTSCSGSLRGLN
  PPHRVKSISMTTFTQQEIEFLQKHGNEVCKQIWLGLFDDRSSAIPDFRDPQKVKEFLQEK
  YEKKRWYVPPEQAKVVASVHASISGSSASSTSSTPEVKPLKSLLGDSAPTLHLNKGTPSQ
  SPVVGRSQGQQQEKKQFDLLSDLGSDIFAAPAPQSTATANFANFAHFNSHAAQNSANADF
  ANFDAFGQSSGSSNFGGFPTASHSPFQPQTTGGSAASVNANFAHFDNFPKSSSADFGTFN
  TSQSHQTASAVSKVSTNKAGLQTADKYAALANLDNIFSAGQGGDQGSGFGTTGKAPVGSV
  VSVPSQSSASSDKYAALAELDSVFSSAATSSNAYTSTSNASSNVFGTVPVVASAQTQPAS
  SSVPAPFGATPSTNPFVAAAGPSVASSTNPFQTNARGATAATFGTASMSMPTGFGTPAPY
  SLPTSFSGSFQQPAFPAQAAFPQQTAFSQQPNGAGFAAFGQTKPVVTPFGQVAAAGVSSN
  PFMTGAPTGQFPTGSSSTNPFL
• Function: Required for vesicle docking or fusion during acrosome biogenesis. May play a role in RNA trafficking or localization. In case of infection by HIV-1, acts as a cofactor for viral Rev and promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm. This step is essential for HIV-1 replication.
• Tissue Specificity: Ubiquitously expressed.
• Reactome Pathway:
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Definitive	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Choroideremia	DISH4N9B	Strong	Biomarker	[10]
Colitis	DISAF7DD	Strong	Biomarker	[11]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[12]
Gastric cancer	DISXGOUK	Strong	Biomarker	[13]
Glioma	DIS5RPEH	Strong	Altered Expression	[14]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[15]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[16]
High blood pressure	DISY2OHH	Strong	Biomarker	[17]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[18]
Myopathy	DISOWG27	Strong	Biomarker	[19]
Nervous system disease	DISJ7GGT	Strong	Biomarker	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[21]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Pancreatic cancer	DISJC981	Strong	Biomarker	[22]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[23]
Parkinson disease	DISQVHKL	Strong	Biomarker	[24]
Prostate cancer	DISF190Y	Strong	Biomarker	[25]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[25]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[26]
Stomach cancer	DISKIJSX	Strong	Biomarker	[13]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[27]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[28]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[29]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[30]
Neoplasm	DISZKGEW	moderate	Biomarker	[31]
Cognitive impairment	DISH2ERD	Disputed	Biomarker	[32]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[33]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[34]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[35]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Biomarker	[36]
Hyperglycemia	DIS0BZB5	Limited	Biomarker	[37]
Liver cancer	DISDE4BI	Limited	Biomarker	[34]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[38]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[39]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[35]

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 Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[40]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[47]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[42]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[44]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[45]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[46]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[48]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Arf-GAP domain and FG repeat-containing protein 1 (AGFG1).	[50]

References

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