importin alpha-1 subunit (karyopherin alpha-1 subunit, KPNA1, suppressor of RNA polymerase 1 mutation, SRP1, SRP1-beta, recombination activating gene (RAG) cohort protein 2, RCH2, nucleoprotein interactor 1, NPI-1)

^[1]^[2]^[3]

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
found in a complex with CSE1L/XPO2, Ran & KPNA2
interacts with CSE1L/XPO2 & NBN
interacts with ANP32E (putative)
forms a complex with importin subunit beta-1

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
- mainly involved in recognition of simple or bipartite NLS motifs
- structurally located within in a helical surface groove
- they contain several conserved Trp & Asn of the corresponding 3rd helices (H3) of ARM repeats which mainly contribute to binding
belongs to the importin alpha family
contains 10 ARM repeats
contains 1 IBB domain

in vitro, mediates nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS
interacts with the nucleoprotein of influenza A viruses
binds to HCMV (human cytomegalovirus) UL84, HIV-1 Vpr & to ebolavirus VP24

↑ Nigg EA, Baeuerle PA, Luhrmann R. Nuclear import-export: in search of signals and mechanisms. Cell. 1991 Jul 12;66(1):15-22. Review. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1712670
↑ Vandromme M et al Regulation of transcription factor localization: fine-tuning of gene expression. Trends Biochem Sci. 1996 Feb;21(2):59-64. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8851662
↑ UniProt http://www.uniprot.org/uniprot/P52294.html