RAE1_DROME
ID RAE1_DROME Reviewed; 346 AA.
AC Q9W2E7; Q7JVX4;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Protein Rae1 {ECO:0000303|PubMed:14729268};
GN Name=Rae1 {ECO:0000303|PubMed:14729268, ECO:0000312|FlyBase:FBgn0034646};
GN ORFNames=CG9862 {ECO:0000312|FlyBase:FBgn0034646};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAM49937.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAM49937.2};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAM49937.2};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14729268; DOI=10.1016/j.gene.2003.10.024;
RA Sitterlin D.;
RT "Characterization of the Drosophila Rae1 protein as a G1 phase regulator of
RT the cell cycle.";
RL Gene 326:107-116(2004).
RN [5] {ECO:0000305}
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH FSN AND HIW, INTERACTION WITH
RP HIW AND NUP98-96, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=21874015; DOI=10.1038/nn.2922;
RA Tian X., Li J., Valakh V., DiAntonio A., Wu C.;
RT "Drosophila Rae1 controls the abundance of the ubiquitin ligase Highwire in
RT post-mitotic neurons.";
RL Nat. Neurosci. 14:1267-1275(2011).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP GLY-129.
RX PubMed=23788425; DOI=10.1242/jcs.111328;
RA Volpi S., Bongiorni S., Fabbretti F., Wakimoto B.T., Prantera G.;
RT "Drosophila rae1 is required for male meiosis and spermatogenesis.";
RL J. Cell Sci. 126:3541-3551(2013).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=27494403; DOI=10.1371/journal.pgen.1006198;
RA Jahanshahi M., Hsiao K., Jenny A., Pfleger C.M.;
RT "The Hippo Pathway Targets Rae1 to Regulate Mitosis and Organ Size and to
RT Feed Back to Regulate Upstream Components Merlin, Hippo, and Warts.";
RL PLoS Genet. 12:E1006198-E1006198(2016).
RN [8] {ECO:0000305}
RP FUNCTION, INTERACTION WITH NUP98-96, AND SUBCELLULAR LOCATION.
RX PubMed=28554770; DOI=10.1016/j.bbamcr.2017.05.020;
RA Kristo I., Bajusz C., Borsos B.N., Pankotai T., Dopie J., Jankovics F.,
RA Vartiainen M.K., Erdelyi M., Vilmos P.;
RT "The actin binding cytoskeletal protein Moesin is involved in nuclear mRNA
RT export.";
RL Biochim. Biophys. Acta 1864:1589-1604(2017).
CC -!- FUNCTION: Probable component of the nuclear pore complex (NPC) which
CC regulates the nuclear export of specific mRNAs and promotes cell cycle
CC progression during mitosis and male meiosis (PubMed:23788425,
CC PubMed:14729268, PubMed:27494403). Acts with Nup98-96 to promote the
CC nuclear export of specific mRNAs such as Moe, however it does not
CC appear to be required for general nuclear mRNA transport
CC (PubMed:14729268, PubMed:28554770). Essential mitotic and male meiotic
CC cell cycle regulator with roles in many aspects of the cell cycle
CC including chromatin organization and condensation, spindle assembly,
CC chromosome segregation, and maintaining nuclear structure
CC (PubMed:23788425, PubMed:14729268, PubMed:27494403). During male
CC meiosis it is required for completion of meiosis I, as well as accurate
CC cytokinesis of the secondary spermatocytes, and postmeiotic
CC differentiation of spermatids (PubMed:23788425). Acts as a downstream
CC regulatory target of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway to
CC promote mitotic cell cycle progression and proliferation during wing
CC and eye development, and thereby plays a key role in integrating the
CC regulation of proliferation with organ size control (PubMed:27494403,
CC PubMed:14729268). When the Hippo/SWH signaling pathway is inactive,
CC Rae1 acts independently of yki to increase organ size by promoting
CC mitotic S-phase entry and increase cellular proliferation
CC (PubMed:27494403). When the Hippo/SWH signaling pathway is active it
CC inhibits the activity of Rae1 in a Wts-dependent manner to restrict
CC organ growth (PubMed:27494403). However, Rae1 is also able to
CC negatively regulate the levels and activity of yki likely by activating
CC the core kinases of the Hippo/SWH signaling pathway hpo and Wts and
CC increasing the protein levels of hpo, Mer and Wts; it is therefore
CC likely that it functions as part of a negative feedback loop with the
CC Hippo/SWH signaling pathway to regulate pathway homeostasis and prevent
CC organ overgrowth (PubMed:27494403). Promotes mitotic cell cycle
CC progression, at least in part, by increasing the accumulation of
CC mitotic cyclins such as CycB, possibly by directly up-regulating cyclin
CC transcripts or by inhibiting the anaphase promoting complex/cyclosome
CC (APC/C) activator fzy (PubMed:27494403). Also required in presynaptic,
CC postmitotic motor neurons to restrain synaptic terminal growth
CC (PubMed:21874015). Promotes the expression and stability of the an E3
CC ubiquitin ligase of hiw, and is likely to function in the regulation of
CC synaptic growth by binding to hiw and protecting it from autophagy-
CC mediated degradation (PubMed:21874015). {ECO:0000269|PubMed:14729268,
CC ECO:0000269|PubMed:21874015, ECO:0000269|PubMed:23788425,
CC ECO:0000269|PubMed:27494403, ECO:0000269|PubMed:28554770}.
CC -!- SUBUNIT: Interacts with hiw; the interaction with Rae1 may protect hiw
CC from autophagy-mediated degradation (PubMed:21874015). Interacts with
CC Nup98-96 (PubMed:21874015, PubMed:28554770).
CC {ECO:0000269|PubMed:21874015, ECO:0000269|PubMed:28554770}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:23788425, ECO:0000269|PubMed:27494403}. Nucleus
CC {ECO:0000269|PubMed:27494403}. Nucleus envelope
CC {ECO:0000269|PubMed:14729268, ECO:0000269|PubMed:23788425}. Chromosome
CC {ECO:0000269|PubMed:23788425, ECO:0000269|PubMed:28554770}. Cytoplasm
CC {ECO:0000269|PubMed:23788425, ECO:0000269|PubMed:27494403}.
CC Note=Dynamic pattern of localization during the spermatocyte cell
CC cycle. Perinuclear in young primary spermatocytes. In late meiotic
CC prophase spermatocytes, localizes to the nucleus where it co-localizes
CC with three major chromatin clumps, and is also associated with puncta
CC in the cytoplasm. In anaphase I and telophase I, occurs at segregating
CC chromatin and mitochondria localized between the two daughter nuclei.
CC In post-meiotic onion stage spermatids, mainly associates with the
CC Nebenkern (a mitochondrial formation in the sperm) but is not detected
CC at the nucleus. {ECO:0000269|PubMed:23788425}.
CC -!- TISSUE SPECIFICITY: Head (at protein level).
CC {ECO:0000269|PubMed:21874015}.
CC -!- DEVELOPMENTAL STAGE: Larval brain (at protein level).
CC {ECO:0000269|PubMed:21874015}.
CC -!- DISRUPTION PHENOTYPE: Larval lethal (PubMed:27494403). Larvae die at
CC the third-instar stage (PubMed:27494403). RNAi-mediated knockdown in
CC the testes results in male sterility likely due to defects in primary
CC spermatocyte nuclear integrity, meiotic chromosome condensation,
CC segregation, and spindle morphology (PubMed:23788425). These defects
CC lead to a failure to complete meiosis but several aspects of spermatid
CC differentiation can still proceed, including axoneme formation and
CC elongation (PubMed:23788425). RNAi-mediated knockdown in the developing
CC wing or in the proliferating cells of the developing eye, reduces their
CC organ size (PubMed:27494403). RNAi-mediated knockdown in larval
CC neuroblasts results in chromatin undercondensation in metaphase
CC chromosomes (PubMed:23788425). RNAi-mediated knockdown in
CC differentiating eye cells does not result in an obvious phenotype
CC (PubMed:27494403). {ECO:0000269|PubMed:23788425,
CC ECO:0000269|PubMed:27494403}.
CC -!- SIMILARITY: Belongs to the WD repeat rae1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM49937.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE013599; AAF46745.1; -; Genomic_DNA.
DR EMBL; AY118568; AAM49937.2; ALT_INIT; mRNA.
DR RefSeq; NP_611597.1; NM_137753.3.
DR AlphaFoldDB; Q9W2E7; -.
DR SMR; Q9W2E7; -.
DR IntAct; Q9W2E7; 2.
DR MINT; Q9W2E7; -.
DR STRING; 7227.FBpp0071600; -.
DR PaxDb; Q9W2E7; -.
DR PRIDE; Q9W2E7; -.
DR DNASU; 37467; -.
DR EnsemblMetazoa; FBtr0071683; FBpp0071600; FBgn0034646.
DR GeneID; 37467; -.
DR KEGG; dme:Dmel_CG9862; -.
DR UCSC; CG9862-RA; d. melanogaster.
DR CTD; 8480; -.
DR FlyBase; FBgn0034646; Rae1.
DR VEuPathDB; VectorBase:FBgn0034646; -.
DR eggNOG; KOG0647; Eukaryota.
DR GeneTree; ENSGT00950000183091; -.
DR HOGENOM; CLU_038526_1_0_1; -.
DR InParanoid; Q9W2E7; -.
DR OMA; EAMDQSI; -.
DR OrthoDB; 1048963at2759; -.
DR PhylomeDB; Q9W2E7; -.
DR Reactome; R-DME-159227; Transport of the SLBP independent Mature mRNA.
DR Reactome; R-DME-159230; Transport of the SLBP Dependant Mature mRNA.
DR Reactome; R-DME-159231; Transport of Mature mRNA Derived from an Intronless Transcript.
DR Reactome; R-DME-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript.
DR Reactome; R-DME-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-DME-3301854; Nuclear Pore Complex (NPC) Disassembly.
DR Reactome; R-DME-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-DME-4085377; SUMOylation of SUMOylation proteins.
DR Reactome; R-DME-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-DME-4615885; SUMOylation of DNA replication proteins.
DR Reactome; R-DME-5578749; Transcriptional regulation by small RNAs.
DR SignaLink; Q9W2E7; -.
DR BioGRID-ORCS; 37467; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 37467; -.
DR PRO; PR:Q9W2E7; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0034646; Expressed in secondary oocyte and 22 other tissues.
DR Genevisible; Q9W2E7; DM.
DR GO; GO:0071944; C:cell periphery; IDA:UniProtKB.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016006; C:Nebenkern; IDA:FlyBase.
DR GO; GO:0005635; C:nuclear envelope; IDA:FlyBase.
DR GO; GO:0005643; C:nuclear pore; IPI:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0036126; C:sperm flagellum; IDA:FlyBase.
DR GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0035329; P:hippo signaling; IMP:FlyBase.
DR GO; GO:0007141; P:male meiosis I; IMP:FlyBase.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:FlyBase.
DR GO; GO:0045886; P:negative regulation of synaptic assembly at neuromuscular junction; IMP:FlyBase.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0035332; P:positive regulation of hippo signaling; IMP:FlyBase.
DR GO; GO:0010506; P:regulation of autophagy; IMP:FlyBase.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0048638; P:regulation of developmental growth; IMP:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IMP:FlyBase.
DR GO; GO:0035330; P:regulation of hippo signaling; IMP:UniProtKB.
DR GO; GO:0006405; P:RNA export from nucleus; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IMP:FlyBase.
DR GO; GO:0000972; P:transcription-dependent tethering of RNA polymerase II gene DNA at nuclear periphery; IBA:GO_Central.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR037631; Gle2/RAE1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR10971:SF11; PTHR10971:SF11; 1.
DR Pfam; PF00400; WD40; 4.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 4.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 4.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Chromosome; Cytoplasm; Differentiation; Meiosis;
KW Mitosis; Nucleus; Reference proteome; Repeat; Spermatogenesis; Transport;
KW WD repeat.
FT CHAIN 1..346
FT /note="Protein Rae1"
FT /id="PRO_0000450094"
FT REPEAT 17..61
FT /note="WD 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 64..105
FT /note="WD 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 126..148
FT /note="WD 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 255..289
FT /note="WD 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT MUTAGEN 129
FT /note="G->D: Male sterility. Spermatocytes display various
FT defects during early meiotic stages, post-meiotic stages
FT and late spermatogenesis. Defects in early meiotic stages
FT result in karyokinesis and cytokinesis abnormailities and a
FT failure to complete meiosis I. Differentiation arrest prior
FT to spermatid individualization results in seminal vesicles
FT lacking mature sperm."
FT /evidence="ECO:0000269|PubMed:23788425"
SQ SEQUENCE 346 AA; 38618 MW; 17E4650B83E692A2 CRC64;
MFGATQSTNR MNDFEVASPP DDSVSALEFS PSTVQKNFLV AGSWDSTVRC WEVEQNGATV
PKSMKTMGGP VLDVCWSDDG SKVFVASCDK QVKLWDLASD QVMQVAAHDG PVKTCHMVKG
PTYTCLMTGS WDKTLKFWDT RSPNPMMTIN LPERCYCADV EYPMAVVGTA NRGLIIYSLQ
NSPTEYKRQE SPLKYQHRAI SIFRDKKKEP TGCALGSIEG RVAIQYVNPG NPKDNFTFKC
HRTTGTSGYQ DIYAVNDIAF HPVHGTLVTV GSDGTFSFWD KDARTKLKSS ETMDQSITKC
GFNANGQIFA YAVGYDWSKG HEYFNPAKKP QIFLRSCYDE LKPRIN
