Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS8T6A7)

• DOT Name: Programmed cell death 6-interacting protein (PDCD6IP)
• Synonyms: PDCD6-interacting protein; ALG-2-interacting protein 1; ALG-2-interacting protein X; Hp95
• Gene Name: PDCD6IP
• Related Disease:
  Adenoma
  Amyloidosis
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Cholangiocarcinoma
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Lung cancer
  Lung carcinoma
  Microcephaly 29, primary, autosomal recessive
  Non-small-cell lung cancer
  Ocular melanoma
  Renal fibrosis
  West syndrome
  Atherosclerosis
  Melanoma
  Arteriosclerosis
  Glioblastoma multiforme
  Human papillomavirus infection
  Osteoarthritis
• UniProt ID: PDC6I_HUMAN
• PDB ID: 2OEV; 2OEW; 2OEX; 2OJQ; 2R02; 2R03; 2R05; 2XS1; 2XS8; 2ZNE; 3C3O; 3C3Q; 3C3R; 3E1R; 3WUV; 4JJY; 5V3R; 5WA1; 6KP3
• Pfam ID: PF13949 ; PF03097
• Sequence:
  MATFISVQLKKTSEVDLAKPLVKFIQQTYPSGGEEQAQYCRAAEELSKLRRAAVGRPLDK
  HEGALETLLRYYDQICSIEPKFPFSENQICLTFTWKDAFDKGSLFGGSVKLALASLGYEK
  SCVLFNCAALASQIAAEQNLDNDEGLKIAAKHYQFASGAFLHIKETVLSALSREPTVDIS
  PDTVGTLSLIMLAQAQEVFFLKATRDKMKDAIIAKLANQAADYFGDAFKQCQYKDTLPKE
  VFPVLAAKHCIMQANAEYHQSILAKQQKKFGEEIARLQHAAELIKTVASRYDEYVNVKDF
  SDKINRALAAAKKDNDFIYHDRVPDLKDLDPIGKATLVKSTPVNVPISQKFTDLFEKMVP
  VSVQQSLAAYNQRKADLVNRSIAQMREATTLANGVLASLNLPAAIEDVSGDTVPQSILTK
  SRSVIEQGGIQTVDQLIKELPELLQRNREILDESLRLLDEEEATDNDLRAKFKERWQRTP
  SNELYKPLRAEGTNFRTVLDKAVQADGQVKECYQSHRDTIVLLCKPEPELNAAIPSANPA
  KTMQGSEVVNVLKSLLSNLDEVKKEREGLENDLKSVNFDMTSKFLTALAQDGVINEEALS
  VTELDRVYGGLTTKVQESLKKQEGLLKNIQVSHQEFSKMKQSNNEANLREEVLKNLATAY
  DNFVELVANLKEGTKFYNELTEILVRFQNKCSDIVFARKTERDELLKDLQQSIAREPSAP
  SIPTPAYQSSPAGGHAPTPPTPAPRTMPPTKPQPPARPPPPVLPANRAPSATAPSPVGAG
  TAAPAPSQTPGSAPPPQAQGPPYPTYPGYPGYCQMPMPMGYNPYAYGQYNMPYPPVYHQS
  PGQAPYPGPQQPSYPFPQPPQQSYYPQQ
• Function: Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity. Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complexes. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis. May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP. By interacting with F-actin, PARD3 and TJP1 secures the proper assembly and positioning of actomyosin-tight junction complex at the apical sides of adjacent epithelial cells that defines a spatial membrane domain essential for the maintenance of epithelial cell polarity and barrier; (Microbial infection) Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function requires the interaction with CHMP4B. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as enveloped virus budding (HIV-1 and other lentiviruses).
• KEGG Pathway:
  Viral life cycle - HIV-1 (hsa03250)
  Endocytosis (hsa04144)
• Reactome Pathway:
  Uptake and function of anthrax toxins (R-HSA-5210891)
  RIPK1-mediated regulated necrosis (R-HSA-5213460)
  Regulation of necroptotic cell death (R-HSA-5675482)
  Budding and maturation of HIV virion (R-HSA-162588)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Altered Expression	[1]
Amyloidosis	DISHTAI2	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[4]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[8]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[6]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[9]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[9]
Microcephaly 29, primary, autosomal recessive	DISQFIMU	Strong	Autosomal recessive	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[11]
Ocular melanoma	DISOHHFC	Strong	Biomarker	[12]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[13]
West syndrome	DISLIAU9	Strong	Genetic Variation	[14]
Atherosclerosis	DISMN9J3	moderate	Altered Expression	[15]
Melanoma	DIS1RRCY	moderate	Genetic Variation	[16]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[17]
Glioblastoma multiforme	DISK8246	Limited	Altered Expression	[18]
Human papillomavirus infection	DISX61LX	Limited	Biomarker	[19]
Osteoarthritis	DIS05URM	Limited	Biomarker	[20]

17 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 Programmed cell death 6-interacting protein (PDCD6IP).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[23]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[24]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[25]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[26]
Hesperetin	DMKER83	Approved	Hesperetin decreases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[27]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[28]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[29]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[30]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[31]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[32]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[33]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[34]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[35]
1,4-Dithiothreitol	DMIFOXE	Investigative	1,4-Dithiothreitol increases the expression of Programmed cell death 6-interacting protein (PDCD6IP).	[30]

References

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