Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU7FOE6)

• DOT Name: Importin subunit alpha-1 (KPNA2)
• Synonyms: Karyopherin subunit alpha-2; RAG cohort protein 1; SRP1-alpha
• Gene Name: KPNA2
• Related Disease:
  Adult glioblastoma
  Carcinoma of liver and intrahepatic biliary tract
  Gallbladder cancer
  Gallbladder carcinoma
  Glioblastoma multiforme
  Liver cancer
  Adenoma
  Advanced cancer
  Astrocytoma
  Bladder cancer
  Castration-resistant prostate carcinoma
  Cholangiocarcinoma
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Colorectal carcinoma
  Dengue
  Diabetic kidney disease
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Gastric adenocarcinoma
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Nijmegen breakage syndrome
  Non-small-cell lung cancer
  Oral cavity squamous cell carcinoma
  Osteoarthritis
  Prostate cancer
  Prostate carcinoma
  Retinoblastoma
  Silver-Russell syndrome
  Stomach cancer
  Transitional cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Urothelial carcinoma
  Ductal breast carcinoma in situ
  Plasma cell myeloma
  Lung adenocarcinoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Clear cell renal carcinoma
  Renal cell carcinoma
  Rheumatoid arthritis
• UniProt ID: IMA1_HUMAN
• PDB ID: 1EFX; 1QGK; 1QGR; 3FEX; 3FEY; 3WPT; 4E4V; 4WV6; 5H43; 7CRU; 7N8J; 7N9H; 8FZK
• Pfam ID: PF00514 ; PF16186 ; PF01749
• Sequence:
  MSTNENANTPAARLHRFKNKGKDSTEMRRRRIEVNVELRKAKKDDQMLKRRNVSSFPDDA
  TSPLQENRNNQGTVNWSVDDIVKGINSSNVENQLQATQAARKLLSREKQPPIDNIIRAGL
  IPKFVSFLGRTDCSPIQFESAWALTNIASGTSEQTKAVVDGGAIPAFISLLASPHAHISE
  QAVWALGNIAGDGSVFRDLVIKYGAVDPLLALLAVPDMSSLACGYLRNLTWTLSNLCRNK
  NPAPPIDAVEQILPTLVRLLHHDDPEVLADTCWAISYLTDGPNERIGMVVKTGVVPQLVK
  LLGASELPIVTPALRAIGNIVTGTDEQTQVVIDAGALAVFPSLLTNPKTNIQKEATWTMS
  NITAGRQDQIQQVVNHGLVPFLVSVLSKADFKTQKEAVWAVTNYTSGGTVEQIVYLVHCG
  IIEPLMNLLTAKDTKIILVILDAISNIFQAAEKLGETEKLSIMIEECGGLDKIEALQNHE
  NESVYKASLSLIEKYFSVEEEEDQNVVPETTSEGYTFQVQDGAPGTFNF
• Function: Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.
• Tissue Specificity: Expressed ubiquitously.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  Influenza A (hsa05164)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  ISG15 antiviral mechanism (R-HSA-1169408)
  NS1 Mediated Effects on Host Pathways (R-HSA-168276)
  CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde (R-HSA-442729)
  Sensing of DNA Double Strand Breaks (R-HSA-5693548)
  Estrogen-dependent gene expression (R-HSA-9018519)
  SARS-CoV-1 activates/modulates innate immune responses (R-HSA-9692916)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  CaMK IV-mediated phosphorylation of CREB (R-HSA-111932)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Biomarker	[2]
Gallbladder cancer	DISXJUAF	Definitive	Altered Expression	[3]
Gallbladder carcinoma	DISD6ACL	Definitive	Altered Expression	[3]
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[1]
Liver cancer	DISDE4BI	Definitive	Biomarker	[2]
Adenoma	DIS78ZEV	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Astrocytoma	DISL3V18	Strong	Biomarker	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Altered Expression	[8]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[11]
Dengue	DISKH221	Strong	Biomarker	[12]
Diabetic kidney disease	DISJMWEY	Strong	Posttranslational Modification	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[14]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[15]
Gastric adenocarcinoma	DISWWLTC	Strong	Altered Expression	[16]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[17]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[18]
Lung cancer	DISCM4YA	Strong	Altered Expression	[19]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[19]
Nijmegen breakage syndrome	DIS98HVL	Strong	Altered Expression	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[19]
Oral cavity squamous cell carcinoma	DISQVJVA	Strong	Altered Expression	[21]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[22]
Prostate cancer	DISF190Y	Strong	Altered Expression	[23]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[8]
Retinoblastoma	DISVPNPB	Strong	Genetic Variation	[24]
Silver-Russell syndrome	DISSVJ1D	Strong	Genetic Variation	[25]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[17]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[26]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[7]
Urothelial carcinoma	DISRTNTN	Strong	Altered Expression	[26]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Altered Expression	[27]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[28]
Lung adenocarcinoma	DISD51WR	Disputed	Biomarker	[29]
Breast cancer	DIS7DPX1	Limited	Biomarker	[30]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[30]
Breast neoplasm	DISNGJLM	Limited	Altered Expression	[31]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[32]
Renal cell carcinoma	DISQZ2X8	Limited	Altered Expression	[32]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Importin subunit alpha-1 (KPNA2) affects the response to substance of Vinblastine.	[60]

26 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 Importin subunit alpha-1 (KPNA2).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Importin subunit alpha-1 (KPNA2).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Importin subunit alpha-1 (KPNA2).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Importin subunit alpha-1 (KPNA2).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Importin subunit alpha-1 (KPNA2).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Importin subunit alpha-1 (KPNA2).	[39]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Importin subunit alpha-1 (KPNA2).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Importin subunit alpha-1 (KPNA2).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Importin subunit alpha-1 (KPNA2).	[42]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Importin subunit alpha-1 (KPNA2).	[43]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Importin subunit alpha-1 (KPNA2).	[44]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Importin subunit alpha-1 (KPNA2).	[45]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Importin subunit alpha-1 (KPNA2).	[46]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Importin subunit alpha-1 (KPNA2).	[47]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Importin subunit alpha-1 (KPNA2).	[45]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Importin subunit alpha-1 (KPNA2).	[48]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Importin subunit alpha-1 (KPNA2).	[49]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Importin subunit alpha-1 (KPNA2).	[50]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Importin subunit alpha-1 (KPNA2).	[45]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Importin subunit alpha-1 (KPNA2).	[51]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Importin subunit alpha-1 (KPNA2).	[38]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Importin subunit alpha-1 (KPNA2).	[46]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Importin subunit alpha-1 (KPNA2).	[55]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Importin subunit alpha-1 (KPNA2).	[56]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Importin subunit alpha-1 (KPNA2).	[58]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Importin subunit alpha-1 (KPNA2).	[59]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin affects the localization of Importin subunit alpha-1 (KPNA2).	[52]
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Importin subunit alpha-1 (KPNA2).	[53]

2 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 Importin subunit alpha-1 (KPNA2).	[54]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Importin subunit alpha-1 (KPNA2).	[57]

References

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