In human importin [alpha], for example, there exists an [alpha]1 subfamily (importin [alpha]5 (KPNA1), [alpha]6 (KPNA5), and [alpha]7 (KPNA6)), [alpha]2 subfamily (importin [alpha]1 (KPNA2) and [alpha]8 (KPNA7)), and [alpha]3 subfamily (importin [alpha]3 (KPNA4) and [alpha]4 (KPNA3)) (Fig.
To avoid confusion, we primarily use the terms KPNA1 to KPNA7 below to refer to human and mouse importin subtypes, because the same term is used for human and mouse homologues.
For example, the expression patterns of importin [alpha] subtypes were shown to change during cell differentiation processes, and, more importantly, its modulation clearly affects cell differentiation processes such as the differentiation of embryonic stem cells into neural cells (KPNA1 (73)), myoblasts into myotubes (KPNA2 (77)), or maturation of oligodendrocyte progenitors (KPNA1, (80) KPNA4 (78)).
(81) Analysis of KPNA1 knockout mice further revealed that KPNA1 is important for muscle regeneration.
Unexpectedly, it has been demonstrated that KPNA1 also functions in the retrograde transport of molecules for axonal injury signaling.
Importin [alpha] molecules (KPNA1, KPNA2, and KPNA3) also exist in cytoplasmic stress granules (SGs) that were induced by arsenite or heat shock.
p value Pathway name Genes 5.27E--7 Detoxification of reactive txn, gstp1, prdx1, gsr, oxygen species gpx1b, prdx5, gpx1a 5.22E--5 Glutathione conjugation gclc, gsto2, gstp1, gclm, gsta.1 6.47E--4 Reduction of cytosolic Ca++ atp2b2, calm3a levels 7.86B--4 Apoptosis lmna, tradd, psma3, psmb7, psma5#, tp53bp2a, kpna1
, prkcdb 1.04B--3 Programmed cell death lmna, tradd, psma3, psmb7, psma5#, tp53bp2a, kpna1
, prkcdb 5.09E--3 Degradation of GLI1 by the tpk1, psma3, psmb7, psma5# proteasome 5.09E--3 GLI3 is processed to GLI3R tpk1, psma3, psmb7, psma5# by the proteasome 5.09E--3 Degradation of GLI2 by the tpk1, psma3, psmb7, psma5# proteasome 5.99E--3 Gluconeogenesis pcxb,fbp1a, pck1, tpk1 7.01 E--3 CaM pathway tpk1, calm3a, prkcdb Bold genes encode proteasome subunits.