importin alpha-3 subunit (karyopherin alpha-3 subunit, KPNA3)
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Function
- nuclear protein import as an adapter protein for nuclear receptor KPNB1
- binds specifically & directly to substrates containing either a simple or bipartite NLS motif
- docking of the importin/substrate complex to the nuclear pore complex is mediated by KPNB1 through binding to nucleoporin FxFG repeats
- the complex is subsequently translocated through the pore by an energy requiring, Ran- dependent mechanism
- at the nucleoplasmic side of the nuclear pore complex, Ran binds to importin-beta & the 3 components separate
- importin-alpha & importin-beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin
- directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- & GDP-bound forms of Ran between the cytoplasm & nucleus
- forms a complex with importin subunit beta-1
Structure
- consists of
- N-terminal hydrophilic region
- hydrophobic central region composed of 10 repeats
- short hydrophilic C-terminus
- N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta & essential for nuclear protein import
- the IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS
- binding of KPNB1 probably overlaps the internal NLS & contributes to a high affinity for cytoplasmic NLS- containing cargo substrates
- after dissociation of the importin/substrate complex in the nucleus, the internal autohibitory NLS contributes to a low affinity for nuclear NLS- containing proteins (putative)
- the major & minor NLS binding sites
- belongs to the importin alpha family
- contains 10 ARM repeats
- contains 1 IBB domain
Compartment
Expression
- ubiquitous.
- highest levels in heart & skeletal muscle
Pathology
- in vitro, mediates nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS
- recognizes NLSs of influenza A virus nucleoprotein probably through ARM repeats 7-9