KPNA1 Antibody - #DF6587

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. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.

Polyubiquitinated in the presence of RAG1 (in vitro).

Cytoplasm. Nucleus.

Expressed ubiquitously.

Heterodimer; with KPNB1. Interacts with ANP32E (By similarity). Interacts with ZIC3 (By similarity). Interacts with NSMF; the interaction occurs in a calcium-independent manner after synaptic NMDA receptor stimulation and is required for nuclear import of NSMF but is competed by CABP1 (By similarity). Interacts with APEX1. Interacts with RAG1. Interacts with CTNNBL1 (via its N-terminal). Interacts with AICDA (via its NLS). Interacts with SNAI1 (via zinc fingers). Interacts with DCAF8. Interacts with ITSN1 isoform 2.

(Microbial infection) Interacts with human cytomegalovirus/HCMV UL84.

(Microbial infection) Interacts with HIV-1 Vpr.

(Microbial infection) Interacts with ebolavirus protein VP24.

(Microbial infection) Interacts with the venezuelan equine encephalitis virus protease nsP2; this interaction probably allows the active transport of protease nsP2 into the host nucleus.

Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and 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 and 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 (By similarity).

The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding (By similarity).

Belongs to the importin alpha family.