IPO7

Description

The IPO7 (importin 7) is a protein-coding gene located on chromosome 11.

Importin-7 is a protein that in humans is encoded by the IPO7 gene. The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. The protein encoded by this gene is a member of a class of approximately 20 potential Ran targets that share a sequence motif related to the Ran-binding site of importin-beta. Similar to importin-beta, this protein prevents the activation of Ran's GTPase by RanGAP1 and inhibits nucleotide exchange on RanGTP, and also binds directly to nuclear pore complexes where it competes for binding sites with importin-beta and transportin. This protein has a Ran-dependent transport cycle and it can cross the nuclear envelope rapidly and in both directions. At least four importin beta-like transport receptors, namely importin beta itself, transportin, RanBP5 and RanBP7, directly bind and import ribosomal proteins.

Importin-7 (IPO7), also known as Ran-binding protein 7, plays a crucial role in nuclear protein import. It can act independently as a nuclear transport receptor or collaborate with the importin-beta subunit KPNB1. When acting autonomously, IPO7 functions as a receptor for nuclear localization signals (NLS) and facilitates the translocation of import substrates through the nuclear pore complex (NPC) using a Ran-dependent mechanism. This process involves the binding of Ran to importin at the nucleoplasmic side of the NPC, leading to the dissociation of the importin/substrate complex. Subsequently, importin is re-exported from the nucleus to the cytoplasm, where GTP hydrolysis releases Ran. The directionality of nuclear import is attributed to the asymmetrical distribution of Ran's GTP- and GDP-bound forms between the cytoplasm and nucleus. IPO7 independently mediates the nuclear import of ribosomal proteins RPL23A, RPS7, and RPL5. In conjunction with KPNB1, it mediates the nuclear import of H1 histone, with the Ran-binding site of IPO7 not being essential but synergizing with KPNB1 in importin/substrate complex dissociation. IPO7 promotes odontoblast differentiation by facilitating the nuclear translocation of DLX3, KLF4, and SMAD2, consequently enhancing the transcription of genes associated with odontoblast differentiation. Furthermore, it assists BMP4-induced translocation of SMAD1 to the nucleus and its recruitment to the MSX1 gene promoter, promoting the expression of the odontogenic regulator MSX1 in dental mesenchymal cells. IPO7 also contributes to odontoblast differentiation by facilitating the nuclear translocation of HDAC6 and subsequent repression of RUNX2 expression. In contrast, IPO7 inhibits osteoblast differentiation by hindering the nuclear translocation of RUNX2, thereby suppressing the transcription of RUNX2 target genes. In vitro, IPO7 mediates the nuclear import of histones H2A, H2B, H3, and H4. {ECO:0000250|UniProtKB:Q9EPL8, ECO:0000269|PubMed:10228156, ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:9687515}

IPO7 is also known as Imp7, RANBP7.

Associated Diseases

WES Whole Exome Sequencing