MXT_DROME
ID MXT_DROME Reviewed; 653 AA.
AC Q9VR35; E1JHT5;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Eukaryotic translation initiation factor 4E-binding protein Mextli {ECO:0000303|PubMed:23716590};
GN Name=mxt {ECO:0000312|FlyBase:FBgn0031637};
GN ORFNames=CG2950 {ECO:0000312|FlyBase:FBgn0031637};
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:AAO25062.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAO25062.1};
RC TISSUE=Head {ECO:0000312|EMBL:AAO25062.1};
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, INTERACTION WITH EIF-4E; EIF3-S9; EIF-3P40; INT6 AND CG3225,
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=23716590; DOI=10.1128/mcb.01354-12;
RA Hernandez G., Miron M., Han H., Liu N., Magescas J., Tettweiler G.,
RA Frank F., Siddiqui N., Sonenberg N., Lasko P.;
RT "Mextli is a novel eukaryotic translation initiation factor 4E-binding
RT protein that promotes translation in Drosophila melanogaster.";
RL Mol. Cell. Biol. 33:2854-2864(2013).
RN [5] {ECO:0007744|PDB:5ABU, ECO:0007744|PDB:5ABV}
RP X-RAY CRYSTALLOGRAPHY (2.13 ANGSTROMS) OF 577-640 IN COMPLEX WITH EIF-4E,
RP INTERACTION WITH EIF-4E, DOMAIN, AND MUTAGENESIS OF TYR-581;
RP 586-LEU-LEU-587; LEU-598; TRP-602 AND MET-605.
RX PubMed=26294658; DOI=10.1101/gad.269068.115;
RA Peter D., Weber R., Kone C., Chung M.Y., Ebertsch L., Truffault V.,
RA Weichenrieder O., Igreja C., Izaurralde E.;
RT "Mextli proteins use both canonical bipartite and novel tripartite binding
RT modes to form eIF4E complexes that display differential sensitivity to 4E-
RT BP regulation.";
RL Genes Dev. 29:1835-1849(2015).
CC -!- FUNCTION: Plays a role in promoting translation.
CC {ECO:0000269|PubMed:23716590}.
CC -!- SUBUNIT: Interacts with eukaryotic translation initiation factor eIF4E1
CC (PubMed:23716590, PubMed:26294658). Also interacts with eukaryotic
CC translation initiation factor 3 complex members eif3-S9/eif3b,
CC Int6/eif3e and eIF-3p40/eif3h and with CG3225 (PubMed:23716590).
CC {ECO:0000269|PubMed:23716590, ECO:0000269|PubMed:26294658}.
CC -!- INTERACTION:
CC Q9VR35; Q9VL73: Dmel\CG13124; NbExp=3; IntAct=EBI-151445, EBI-113702;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23716590}. Note=In
CC germ line cells, predominantly cytoplasmic and accumulates in the
CC perinuclear nuage during oogenesis but disappears from there around
CC stage 8. {ECO:0000269|PubMed:23716590}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A {ECO:0000312|FlyBase:FBgn0031637}; Synonyms=B
CC {ECO:0000312|FlyBase:FBgn0031637}, C {ECO:0000312|FlyBase:FBgn0031637},
CC E {ECO:0000312|FlyBase:FBgn0031637};
CC IsoId=Q9VR35-1; Sequence=Displayed;
CC Name=D {ECO:0000312|FlyBase:FBgn0031637};
CC IsoId=Q9VR35-2; Sequence=VSP_058328;
CC -!- DEVELOPMENTAL STAGE: Expressed throughout oogenesis with particularly
CC high levels in germ line stem cells and cystoblasts and decreasing
CC levels in subsequent divisions. Around stage 8, remains detectable in
CC nurse cells and oocytes and expression increases in follicle cells
CC where it persists until late oogenesis, both in stretched cells and in
CC columnar follicle cells (at protein level).
CC {ECO:0000269|PubMed:23716590}.
CC -!- DOMAIN: Binds to eIF4E1 using a novel tripartite interface in the C-
CC terminal domain comprising a canonical helix which engages the eIF4E1
CC dorsal surface, a non-canonical helix which engages the eIF4E1 lateral
CC surface and an auxiliary helix that lies anti-parallel to the canonical
CC helix on the eIF4E1 dorsal surface. The tripartite binding mode
CC compromises its ability to compete with eIF4G1 for binding to eIF4E1
CC but once bound, the complex is very stable and is resistant to
CC competition by eIF4G1. {ECO:0000269|PubMed:26294658}.
CC -!- DISRUPTION PHENOTYPE: Mutants are viable and fertile but 14-21% of
CC embryos fail to hatch, displaying variable segmentation defects
CC affecting anterior-posterior patterning. Mutant ovaries are generally
CC smaller with fewer late-stage oocytes than controls and females lay
CC fewer eggs. Reduced cap-dependent translation.
CC {ECO:0000269|PubMed:23716590}.
CC -!- MISCELLANEOUS: The name 'Mextli' derives from the Aztec god of storms
CC and war. {ECO:0000303|PubMed:23716590}.
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DR EMBL; AE014134; AAF50972.1; -; Genomic_DNA.
DR EMBL; AE014134; AAF50973.1; -; Genomic_DNA.
DR EMBL; AE014134; AAN10338.1; -; Genomic_DNA.
DR EMBL; AE014134; ACZ94165.1; -; Genomic_DNA.
DR EMBL; AE014134; AGB92589.1; -; Genomic_DNA.
DR EMBL; BT003302; AAO25062.1; -; mRNA.
DR RefSeq; NP_001162874.1; NM_001169403.2. [Q9VR35-2]
DR RefSeq; NP_001260053.1; NM_001273124.1. [Q9VR35-1]
DR RefSeq; NP_608866.1; NM_135022.3. [Q9VR35-1]
DR RefSeq; NP_723015.1; NM_164598.2. [Q9VR35-1]
DR RefSeq; NP_723016.1; NM_164599.2. [Q9VR35-1]
DR PDB; 5ABU; X-ray; 2.16 A; B=577-640.
DR PDB; 5ABV; X-ray; 2.13 A; B/D/F/H=577-640.
DR PDBsum; 5ABU; -.
DR PDBsum; 5ABV; -.
DR AlphaFoldDB; Q9VR35; -.
DR SMR; Q9VR35; -.
DR IntAct; Q9VR35; 15.
DR STRING; 7227.FBpp0290163; -.
DR PaxDb; Q9VR35; -.
DR DNASU; 33686; -.
DR EnsemblMetazoa; FBtr0077409; FBpp0077100; FBgn0031637. [Q9VR35-1]
DR EnsemblMetazoa; FBtr0077410; FBpp0077101; FBgn0031637. [Q9VR35-1]
DR EnsemblMetazoa; FBtr0077411; FBpp0077102; FBgn0031637. [Q9VR35-1]
DR EnsemblMetazoa; FBtr0300941; FBpp0290163; FBgn0031637. [Q9VR35-2]
DR EnsemblMetazoa; FBtr0332477; FBpp0304753; FBgn0031637. [Q9VR35-1]
DR GeneID; 33686; -.
DR KEGG; dme:Dmel_CG2950; -.
DR UCSC; CG2950-RA; d. melanogaster. [Q9VR35-1]
DR CTD; 33686; -.
DR FlyBase; FBgn0031637; mxt.
DR VEuPathDB; VectorBase:FBgn0031637; -.
DR eggNOG; ENOG502QRYP; Eukaryota.
DR GeneTree; ENSGT00520000058221; -.
DR HOGENOM; CLU_029657_0_0_1; -.
DR OMA; HAWALPT; -.
DR PhylomeDB; Q9VR35; -.
DR BioGRID-ORCS; 33686; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 33686; -.
DR PRO; PR:Q9VR35; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0031637; Expressed in crop (Drosophila) and 24 other tissues.
DR ExpressionAtlas; Q9VR35; baseline and differential.
DR Genevisible; E1JHT5; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0034518; C:RNA cap binding complex; IMP:FlyBase.
DR GO; GO:0008190; F:eukaryotic initiation factor 4E binding; IPI:FlyBase.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003743; F:translation initiation factor activity; IMP:FlyBase.
DR GO; GO:0036099; P:female germ-line stem cell population maintenance; IMP:FlyBase.
DR GO; GO:0045727; P:positive regulation of translation; IMP:FlyBase.
DR GO; GO:1901190; P:regulation of formation of translation initiation ternary complex; IMP:FlyBase.
DR Gene3D; 3.30.1370.10; -; 1.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR040160; Mxt.
DR PANTHER; PTHR20849; PTHR20849; 1.
DR Pfam; PF00013; KH_1; 1.
DR SMART; SM00322; KH; 1.
DR SUPFAM; SSF54791; SSF54791; 1.
DR PROSITE; PS50084; KH_TYPE_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Reference proteome;
KW RNA-binding; Translation regulation.
FT CHAIN 1..653
FT /note="Eukaryotic translation initiation factor 4E-binding
FT protein Mextli"
FT /evidence="ECO:0000305"
FT /id="PRO_0000436263"
FT DOMAIN 227..292
FT /note="KH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT REGION 311..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 515..570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 313..335
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 524..540
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 542..566
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 617..653
FT /note="DLQDESQRFDGDKYLASIKTAAKRDIVAADEVETLDE -> VISPFDGSLGR
FT TAYSSNIPDAIIASAPNSSVITHPWALNAITSSPNTNIISTAVGLAAVDASADNNPLTV
FT TNKQSKGIFAERENRRLPKTSAVSDRNLYNKQLQIITNTVGQSVATQGKHRQSSYQTSQ
FT VKAIFQRYCEDDEFSLALCETESNNNRVYV (in isoform D)"
FT /evidence="ECO:0000305"
FT /id="VSP_058328"
FT MUTAGEN 581
FT /note="Y->A: Abolishes interaction with eIF4E1; when
FT associated with 586-A-A-587."
FT /evidence="ECO:0000269|PubMed:26294658"
FT MUTAGEN 586..587
FT /note="LL->AA: Abolishes interaction with eIF4E1; when
FT associated with A-581."
FT /evidence="ECO:0000269|PubMed:26294658"
FT MUTAGEN 598
FT /note="L->D: Abolishes interaction with eIF4E1."
FT /evidence="ECO:0000269|PubMed:26294658"
FT MUTAGEN 602
FT /note="W->D: Abolishes interaction with eIF4E1."
FT /evidence="ECO:0000269|PubMed:26294658"
FT MUTAGEN 605
FT /note="M->D: Abolishes interaction with eIF4E1."
FT /evidence="ECO:0000269|PubMed:26294658"
FT HELIX 583..589
FT /evidence="ECO:0007829|PDB:5ABV"
FT HELIX 593..595
FT /evidence="ECO:0007829|PDB:5ABV"
FT HELIX 602..608
FT /evidence="ECO:0007829|PDB:5ABV"
FT HELIX 610..612
FT /evidence="ECO:0007829|PDB:5ABV"
FT HELIX 627..636
FT /evidence="ECO:0007829|PDB:5ABV"
SQ SEQUENCE 653 AA; 70148 MW; E0C9D54DAA811C0C CRC64;
MAHTHLGRAV KNIEAPRPLK TQSRSSLKNS YLVIEELIQL IDNVTVGLQS CNTTPESITL
LLHNLRVHGP QLEAVSKDTL DRAFVVFRNA SQDERLNITT RLKLLELIEL RAKSWDNDDT
IAYYKSKQQI SNVELPSEYQ YDAGVQPGAF STSPTFGVSG GVGGVNDGAA AAAAAVFNAA
SAAAAAQAAA IAAVGTSNQQ HMLLPPGEVI RNSGKFPKPT KIPGKTYCKD EVVIRNADSG
KVMGIKGRRV HMIEELSETI ISFQRVNPGA KERLVQITGP AEDKINYAKQ LMEDTIRRNA
SPVRLEPAPA VGGSCSSLNS SNSDDAIVQP RTPTGSSLAN RLSFNSAQNF MTATAAAQQI
SQQMHHQTHH LQHQQQQQVA AVAAAAAAAA HAQATAAAGK VLRPNQQLLM HSYSTNDASV
GEYKFTVNVG QHLIKITGDC CELVRVAKLV LDDYFSSSEF LASIEAGAAF DGTSLVTTPS
TPLPGAGPPQ FWLPGTDSGI GLNCVVSSSA NNNGEGDDEV FAEPSNGGSS TSNQNGLARS
RRSHFSRKES TPETKGAREK GDLDDLAGTN SLKSNASRVS YDIEHLLYYS MSPHSWTLPT
DWQKMQETAP SILRNKDLQD ESQRFDGDKY LASIKTAAKR DIVAADEVET LDE
