Domain

Importin-alpha, importin-beta-binding domain (IPR002652)

Short name: Importin-a_IBB

Domain relationships

None.

Description

The exchange of macromolecules between the nucleus and cytoplasm takes place through nuclear pore complexes within the nuclear membrane. Active transport of large molecules through these pore complexes require carrier proteins, called karyopherins (importins and exportins), which shuttle between the two compartments.

Members of the importin-alpha (karyopherin-alpha) family can form heterodimers with importin-beta. As part of a heterodimer, importin-beta mediates interactions with the pore complex, while importin-alpha acts as an adaptor protein to bind the nuclear localisation signal (NLS) on the cargo through the classical NLS import of proteins. Proteins can contain one (monopartite) or two (bipartite) NLS motifs. Importin-alpha contains several armadillo (ARM) repeats, which produce a curving structure with two NLS-binding sites, a major one close to the N terminus and a minor one close to the C terminus.

Ran GTPase helps to control the unidirectional transfer of cargo. The cytoplasm contains primarily RanGDP and the nucleus RanGTP through the actions of RanGAP and RanGEF, respectively. In the nucleus, RanGTP binds to importin-beta within the importin/cargo complex, causing a conformational change in importin-beta that releases it from importin-alpha-bound cargo. The N-terminal importin-beta-binding (IBB) domain of importin-alpha contains an auto-regulatory region that mimics the NLS motif [PMID: 8692858]. The release of importin-beta frees the auto-regulatory region on importin-alpha to loop back and bind to the major NLS-binding site, causing the cargo to be released [PMID: 17170104].

This entry represents the N-terminal IBB domain of importin-alpha that contains the auto-regulatory region.

More information about these proteins can be found at Protein of the Month: Importins [].

GO terms

Biological Process

GO:0006606 protein import into nucleus

Molecular Function

GO:0008565 protein transporter activity

Cellular Component

GO:0005737 cytoplasm
GO:0005634 nucleus

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
GENE3D
Pfam
PROSITE profiles