Disease relevance of KPNA1

• These experiments suggest that NPI-1 plays a role during influenza virus replication [1].
• Nuclear import of Epstein-Barr virus nuclear antigen 1 mediated by NPI-1 (Importin alpha5) is up- and down-regulated by phosphorylation of the nuclear localization signal for which Lys379 and Arg380 are essential [2].

High impact information on KPNA1

• These results indicate that the extracellular signal-dependent nuclear transport of Stat1 is mediated by NPI-1, but not Rch1, in conjunction with beta subunit, and that these factors participate in, not only constitutive, but also the conditional nuclear import of proteins [3].
• This domain is conserved in other SRP1-like proteins and its fusion to a cytoplasmic reporter protein is sufficient to promote complete nuclear import, circumventing the usual requirement for an NLS receptor interaction [4].
• We have found that the karyopherins hSRP1 and hSRP1alpha are differentially expressed in various leukocyte cell lines and could be induced in normal human peripheral blood lymphocytes [5].
• Furthermore, in HeLa cell crude cytosol, it was found that endogenous Rch1 binds to all the tested NLS substrates, while the binding of endogenous NPI-1 is restricted to only some NLSs, despite the fact that NPI-1 itself shows binding activity to a variety of NLSs [6].
• The first step, which is to dock the NLS-containing protein to the nuclear pore, is carried out in part by a recently identified NLS receptor named Srp1/importin-alpha [7].

Biological context of KPNA1

• Assignment of karyopherin alpha 1 (KPNA1) to human chromosome band 3q21 by in situ hybridization [8].
• The karyopherin alpha NPI-1 (importin alpha5), a nuclear import adaptor, bound more strongly to Ser385-phosphorylated NLS than to any other phosphorylated or nonphosphorylated forms [2].
• DNA sequence analysis revealed that the full-length cDNA, encoding rat KPNA1, was 4975 bp with a short 5'-untranslated region (UTR) of 70 bp, a putative coding sequence of 1617 bp, and an unusually long 3'-UTR of 3266 bp [9].
• Exposure of various cell types to high glucose or mannose (25 mmol/L) led to increased expression of importins alpha3, alpha5/hSRP1, and alpha7 in different cultured cells, while up-regulation of other importin alpha isoforms was less consistent [10].
• The phylogeny reveals three Kpna subfamilies with distinct, conserved gene structures, shedding light on the evolutionary origins of this multigene family in metazoa [11].

Anatomical context of KPNA1

• A full-length cDNA clone of NPI-1 was generated from HeLa cell poly A + RNA [1].
• We also demonstrate that Kpna genes are regulated in rat liver and isolated hepatocytes in a xenobiotic-specific manner for a number of chemically distinct liver growth agents [11].

Associations of KPNA1 with chemical compounds

• The viral nucleoprotein, which had been partially purified from influenza A/PR/8/34 virus-infected embryonated eggs, could be coprecipitated from solution by glutathione agarose beads complexed with a bacterially expressed glutathione-S-transferase-NPI-1 fusion protein, confirming the results of the yeast genetic system [1].
• Our results suggest involvement of KPNA1 in the striatal responses to denervation following 6-hydroxydopamine (6-OHDA)-induced lesion [9].
• The characteristic hyperfine triplet is assigned in part to RCH2. radicals from glycine units, which constitute about one-third of the total amino acid components in collagen, and in part to RNHCO radicals [12].

Physical interactions of KPNA1

• Interestingly, IFN-gamma-SV was also translocated to the nucleus and was also recovered intracellularly as a complex with the Stat1alpha importer NPI-1, like wild-type IFN-gamma [13].

Analytical, diagnostic and therapeutic context of KPNA1

• Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that KPNA1 transcript existed in various adult tissues [9].
• METHODS AND RESULTS: Using quantitative PCR, we have analysed Kpna transcript levels in 44 rat tissues; Kpna transcripts show a wide variation in their distribution both in absolute and relative terms, suggestive of specialized roles for each member [11].

References