importin alpha-2 subunit (karyopherin alpha-2 subunit, KPNA2, SRP1-alpha, recombination-activating gene (RAG) cohort protein 1, RCH1)

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) Structure: - consists of a) N-terminal hydrophilic region b) hydrophobic central region composed of 10 repeats c) 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 a) mainly involved in recognition of simple or bipartite NLS motifs b) structurally located within in a helical surface groove c) 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 Compartment: cytoplasm. nucleus Expression: expressed ubiquitously Pathology: - interacts with HIV-1 Vpr & PLAG1

General

importin alpha subunit phosphoprotein

Properties

SIZE: entity length = 529 aa MW = 58 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: IBB {1-60} MOTIF: Ser phosphorylation site {S24} arginine-rich region {28-31} MOTIF: arginine residue (SEVERAL) nuclear translocation signal {45-54} Ser phosphorylation site {S62} ARM repeat {71-111} ARM repeat {112-151} NLS binding site (major) {142-238} MOTIF: ARM repeat {152-193} ARM repeat {200-244} ARM repeat {246-282} ARM repeat {283-322} NLS binding site (minor) {315-403} MOTIF: ARM repeat {325-364} ARM repeat {367-409} ARM repeat {410-456} ARM repeat {457-496} MOTIF: Ser phosphorylation site {S490} glutamate-rich region {499-502} MOTIF: glutamate residue (SEVERAL)

Database Correlations

OMIM 600685 UniProt P52292 Entrez Gene 3838 Kegg hsa:3838