Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTHOJ5F)

• DTT Name: Importin beta (KPNB1)
• Synonyms: Pore targeting complex 97 kDa subunit; PTAC97; Nuclear factor p97; NTF97; Karyopherin subunit beta1; Karyopherin subunit beta-1; Importin90; Importin-90; Importin subunit beta1; Importin subunit beta-1
• Gene Name: KPNB1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Eukaryotic nuclear pore complex
• UniProt ID: IMB1_HUMAN
• TTD ID: T64022
• Sequence:
  MELITILEKTVSPDRLELEAAQKFLERAAVENLPTFLVELSRVLANPGNSQVARVAAGLQ
  IKNSLTSKDPDIKAQYQQRWLAIDANARREVKNYVLQTLGTETYRPSSASQCVAGIACAE
  IPVNQWPELIPQLVANVTNPNSTEHMKESTLEAIGYICQDIDPEQLQDKSNEILTAIIQG
  MRKEEPSNNVKLAATNALLNSLEFTKANFDKESERHFIMQVVCEATQCPDTRVRVAALQN
  LVKIMSLYYQYMETYMGPALFAITIEAMKSDIDEVALQGIEFWSNVCDEEMDLAIEASEA
  AEQGRPPEHTSKFYAKGALQYLVPILTQTLTKQDENDDDDDWNPCKAAGVCLMLLATCCE
  DDIVPHVLPFIKEHIKNPDWRYRDAAVMAFGCILEGPEPSQLKPLVIQAMPTLIELMKDP
  SVVVRDTAAWTVGRICELLPEAAINDVYLAPLLQCLIEGLSAEPRVASNVCWAFSSLAEA
  AYEAADVADDQEEPATYCLSSSFELIVQKLLETTDRPDGHQNNLRSSAYESLMEIVKNSA
  KDCYPAVQKTTLVIMERLQQVLQMESHIQSTSDRIQFNDLQSLLCATLQNVLRKVQHQDA
  LQISDVVMASLLRMFQSTAGSGGVQEDALMAVSTLVEVLGGEFLKYMEAFKPFLGIGLKN
  YAEYQVCLAAVGLVGDLCRALQSNIIPFCDEVMQLLLENLGNENVHRSVKPQILSVFGDI
  ALAIGGEFKKYLEVVLNTLQQASQAQVDKSDYDMVDYLNELRESCLEAYTGIVQGLKGDQ
  ENVHPDVMLVQPRVEFILSFIDHIAGDEDHTDGVVACAAGLIGDLCTAFGKDVLKLVEAR
  PMIHELLTEGRRSKTNKAKTLATWATKELRKLKNQA
• Function: Acting autonomously, serves itself as NLS receptor. 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. Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. Binds to a beta-like import receptor binding (BIB) domain of RPL23A. In association with IPO7 mediates the nuclear import of H1 histone. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. Imports SNAI1 and PRKCI into the nucleus. Functions in nuclear protein import, either in association with an adapter protein, like an importin-alpha subunit, which binds to nuclear localization signals (NLS) in cargo substrates, or by acting as autonomous nuclear transport receptor.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  Apoptosis induced DNA fragmentation (R-HSA-140342)
  Regulation of cholesterol biosynthesis by SREBP (SREBF) (R-HSA-1655829)
  Transport of Ribonucleoproteins into the Host Nucleus (R-HSA-168271)
  NS1 Mediated Effects on Host Pathways (R-HSA-168276)
  Nuclear import of Rev protein (R-HSA-180746)
  Initiation of Nuclear Envelope (NE) Reformation (R-HSA-2995383)
  Neutrophil degranulation (R-HSA-6798695)
  Assembly of the ORC complex at the origin of replication (R-HSA-68616)
  Interferon alpha/beta signaling (R-HSA-909733)
  Postmitotic nuclear pore complex (NPC) reformation (R-HSA-9615933)
  Inhibition of nitric oxide production (R-HSA-9636249)
  ISG15 antiviral mechanism (R-HSA-1169408)

References

• [1] Identification of KPNB1 as a Cellular Target of Aminothiazole Derivatives with Anticancer Activity. ChemMedChem. 2016 Jul 5;11(13):1406-9.