Protein: Protein Rae1 (Q9W2E7)
Organism: Drosophila melanogaster (Fruit fly)
Function: Probable component of the nuclear pore complex (NPC) which regulates the nuclear export of specific mRNAs and promotes cell cycle progression during mitosis and male meiosis. Acts with Nup98-96 to promote the nuclear export of specific mRNAs such as Moe, however it does not appear to be required for general nuclear mRNA transport. Essential mitotic and male meiotic cell cycle regulator with roles in many aspects of the cell cycle including chromatin organization and condensation, spindle assembly, chromosome segregation, and maintaining nuclear structure. During male meiosis it is required for completion of meiosis I, as well as accurate cytokinesis of the secondary spermatocytes, and postmeiotic differentiation of spermatids. Acts as a downstream regulatory target of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway to promote mitotic cell cycle progression and proliferation during wing and eye development, and thereby plays a key role in integrating the regulation of proliferation with organ size control. When the Hippo/SWH signaling pathway is inactive, Rae1 acts independently of yki to increase organ size by promoting mitotic S-phase entry and increase cellular proliferation. When the Hippo/SWH signaling pathway is active it inhibits the activity of Rae1 in a Wts-dependent manner to restrict organ growth. However, Rae1 is also able to negatively regulate the levels and activity of yki likely by activating the core kinases of the Hippo/SWH signaling pathway hpo and Wts and increasing the protein levels of hpo, Mer and Wts; it is therefore likely that it functions as part of a negative feedback loop with the Hippo/SWH signaling pathway to regulate pathway homeostasis and prevent organ overgrowth. Promotes mitotic cell cycle progression, at least in part, by increasing the accumulation of mitotic cyclins such as CycB, possibly by directly up-regulating cyclin transcripts or by inhibiting the anaphase promoting complex/cyclosome (APC/C) activator fzy. Also required in presynaptic, postmitotic motor neurons to restrain synaptic terminal growth. Promotes the expression and stability of the an E3 ubiquitin ligase of hiw, and is likely to function in the regulation of synaptic growth by binding to hiw and protecting it from autophagy-mediated degradation.
Subcellular location: Cytoplasm, perinuclear region {ECO:0000269|PubMed:23788425, ECO:0000269|PubMed:27494403}. Nucleus {ECO:0000269|PubMed:27494403}. Nucleus envelope {ECO:0000269|PubMed:14729268, ECO:0000269|PubMed:23788425}. Chromosome {ECO:0000269|PubMed:23788425, ECO:0000269|PubMed:28554770}. Cytoplasm {ECO:0000269|PubMed:23788425, ECO:0000269|PubMed:27494403}. Note=Dynamic pattern of localization during the spermatocyte cell cycle. Perinuclear in young primary spermatocytes. In late meiotic prophase spermatocytes, localizes to the nucleus where it co-localizes with three major chromatin clumps, and is also associated with puncta in the cytoplasm. In anaphase I and telophase I, occurs at segregating chromatin and mitochondria localized between the two daughter nuclei. In post-meiotic onion stage spermatids, mainly associates with the Nebenkern (a mitochondrial formation in the sperm) but is not detected at the nucleus. {ECO:0000269|PubMed:23788425}.
Interaction partners:
- Nuclear pore complex protein Nup98-Nup96
- Nuclear RNA export factor 1
- Nuclear pore complex protein Nup214
- mRNA export factor Gle1
- Nuclear pore complex protein Nup153
- LD14924p
- Nuclear export factor 4
- Nuclear pore complex protein Nup88
- Nucleoporin seh1
- Nuclear pore complex protein Nup154
Sequence:
MFGATQSTNRMNDFEVASPPDDSVSALEFSPSTVQKNFLVAGSWDSTVRCWEVEQNGATVPKSMKTMGGPVLDVCWSDDGSKVFVASCDKQVKLWDLASDQVMQVAAHDGPVKTCHMVKGPTYTCLMTGSWDKTLKFWDTRSPNPMMTINLPERCYCADVEYPMAVVGTANRGLIIYSLQNSPTEYKRQESPLKYQHRAISIFRDKKKEPTGCALGSIEGRVAIQYVNPGNPKDNFTFKCHRTTGTSGYQDIYAVNDIAFHPVHGTLVTVGSDGTFSFWDKDARTKLKSSETMDQSITKCGFNANGQIFAYAVGYDWSKGHEYFNPAKKPQIFLRSCYDELKPRIN