Target intelligence / Profile preview

Karyopherin subunit alpha 1 (Importin subunit alpha-5) (KPNA1)

Target
KPNA1
Molecular classification
Transporter (Nuclear import receptor), Armadillo repeat-containing protein, Importin family
01

Overview

Karyopherin subunit alpha 1 (KPNA1, Importin subunit alpha-5) is a key adaptor protein in the classical nuclear import pathway, recognizing and binding nuclear localization signals (NLS) on cargo proteins, and bridging them to importin-beta (KPNB1) for energy-dependent translocation through the nuclear pore complex. KPNA1 is essential for the nuclear import of regulatory proteins involved in cell proliferation, apoptosis, and immune response, including phosphorylated STAT1 and p27. It also mediates the nuclear import of certain viral proteins and is antagonized by viral proteins to evade host immunity. KPNA1's function is critical in muscle satellite cell activation/quiescence and gene expression regulation, with its loss or dysfunction linked to diseases such as viral encephalitis, impaired immune response, and possibly cancer. Its role as a nuclear transporter makes it both a potential therapeutic target and a point of vulnerability for viral pathogens

Other names
Importin subunit alpha-5NPI-1RCH2SRP1IPOA5SRP1-betaKaryopherin alpha 1Importin-alpha-S1Nucleoprotein interactor 1RAG cohort protein 2
02

Mechanism of action

Competitive inhibition of cargo binding (e.g., viral antagonists such as Ebola VP24 compete with STAT1 for KPNA1 binding); Disruption of importin alpha/beta-dependent nuclear transport pathways; Targeting nuclear localization signal (NLS) binding on cargo proteins

03

Biological functions

Nuclear protein importSignal transduction (especially of immune signaling proteins such as phosphorylated STAT1)Cell proliferation and cell cycle regulationApoptosisRegulation of gene expressionIntracellular transport of viral proteins
04

Disease associations

Infection (notably: Venezuelan equine encephalitis, influenza, Ebola, foamy virus, cytomegalovirus)Cancer (roles in cell cycle and proliferation, but limited direct linkage so far)Neurodegenerative disease (possible, through nuclear transport defects, though not primary)Other: Muscle regeneration and satellite cell activation/quiescence
05

Safety considerations

Therapeutic targeting poses risk due to essential roles in nuclear protein import and cell survival.Inhibition could result in cytotoxicity, impaired cell growth, immune dysregulation, and increased susceptibility to viral infection or apoptosis.
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Interacting drugs

Ebola VP24

2 more in the full profile.

07

Biomarkers

KPNA1 expression and/or nuclear import activity may serve as biomarkers for antiviral efficacy, cell cycle status, or cancer risk stratification

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