EGRAP_DROME
ID EGRAP_DROME Reviewed; 421 AA.
AC Q6NR09; Q29QP1;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=EGFR adapter protein {ECO:0000303|PubMed:34411095};
GN Name=EGFRAP {ECO:0000303|PubMed:34411095};
GN ORFNames=CG33993 {ECO:0000312|FlyBase:FBgn0053993};
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:AAQ23593.1, ECO:0000312|EMBL:ABC66161.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
RC TISSUE=Embryo {ECO:0000312|EMBL:AAQ23593.1};
RA Celniker S., Carlson J., Wan K., Frise E., Hoskins R., Park S.,
RA Svirskas R., Rubin G., Stapleton M., Chavez C., George R., Pacleb J.,
RA Yu C.;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=34411095; DOI=10.1371/journal.pgen.1009738;
RA Soler Beatty J., Molnar C., Luque C.M., de Celis J.F., Martin-Bermudo M.D.;
RT "EGFRAP encodes a new negative regulator of the EGFR acting in both normal
RT and oncogenic EGFR/Ras-driven tissue morphogenesis.";
RL PLoS Genet. 17:e1009738-e1009738(2021).
CC -!- FUNCTION: Involved in the negative regulation of the Egfr/Ras signaling
CC pathway (PubMed:34411095). During wing morphogenesis, may function
CC redundantly with PVRAP to inhibit Egfr activity and prevent
CC uncontrolled cell growth (PubMed:34411095).
CC {ECO:0000269|PubMed:34411095}.
CC -!- SUBUNIT: May interact (via SH2 domain) with Egfr (when phosphorylated).
CC {ECO:0000269|PubMed:34411095}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A {ECO:0000312|FlyBase:FBgn0053993};
CC IsoId=Q6NR09-1; Sequence=Displayed;
CC Name=B {ECO:0000312|FlyBase:FBgn0053993};
CC IsoId=Q6NR09-2; Sequence=VSP_061376;
CC -!- TISSUE SPECIFICITY: Detected along the wing margin, with high levels of
CC expression in two stripes of cells on either side of the dorsal/ventral
CC boundary and lower levels of expression in a small region at the
CC anteroposterior boundary (at protein level) (PubMed:34411095). High
CC levels of expression along two parallel stripes of cells on either side
CC of the wing pouch dorsal/ventral boundary, and slightly lower levels of
CC expression in a region either side of the anteroposterior boundary
CC (PubMed:34411095). Also expressed in discrete regions of the wing
CC imaginal disk outside of the pouch (PubMed:34411095). Expressed in eye
CC imaginal disk photoreceptors with highest levels of expression in R7
CC photoreceptor cells (PubMed:34411095). {ECO:0000269|PubMed:34411095}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in adults does not result
CC in a visible phenotype (PubMed:34411095). However, simultaneous
CC knockdown of EGFRAP (CG33993) and PVRAP results in the development of
CC ectopic sensory organs in the notum and blisters in the wings
CC (PubMed:34411095). RNAi-mediated knockdown in the posterior compartment
CC of the wing disks, increases expression of PEK (PubMed:34411095).
CC {ECO:0000269|PubMed:34411095}.
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DR EMBL; AE014296; ABC66161.1; -; Genomic_DNA.
DR EMBL; AE014296; ACZ94623.1; -; Genomic_DNA.
DR EMBL; BT010275; AAQ23593.1; -; mRNA.
DR EMBL; BT024349; ABC86411.1; -; mRNA.
DR RefSeq; NP_001033991.1; NM_001038902.3.
DR AlphaFoldDB; Q6NR09; -.
DR SMR; Q6NR09; -.
DR IntAct; Q6NR09; 2.
DR STRING; 7227.FBpp0099403; -.
DR PaxDb; Q6NR09; -.
DR DNASU; 3885637; -.
DR EnsemblMetazoa; FBtr0100046; FBpp0099403; FBgn0053993. [Q6NR09-1]
DR EnsemblMetazoa; FBtr0301034; FBpp0290256; FBgn0053993. [Q6NR09-2]
DR GeneID; 3885637; -.
DR KEGG; dme:Dmel_CG33993; -.
DR UCSC; CG33993-RA; d. melanogaster. [Q6NR09-1]
DR FlyBase; FBgn0053993; CG33993.
DR VEuPathDB; VectorBase:FBgn0053993; -.
DR eggNOG; ENOG502QR6J; Eukaryota.
DR GeneTree; ENSGT00390000007997; -.
DR HOGENOM; CLU_031830_0_0_1; -.
DR InParanoid; Q6NR09; -.
DR OMA; AMQDIRL; -.
DR OrthoDB; 791930at2759; -.
DR PhylomeDB; Q6NR09; -.
DR BioGRID-ORCS; 3885637; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 3885637; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0053993; Expressed in labral sensory complex primordium (Drosophila) and 30 other tissues.
DR ExpressionAtlas; Q6NR09; baseline and differential.
DR GO; GO:0045179; C:apical cortex; IDA:FlyBase.
DR GO; GO:0005925; C:focal adhesion; IBA:GO_Central.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IMP:FlyBase.
DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IGI:FlyBase.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Reference proteome; SH2 domain.
FT CHAIN 1..421
FT /note="EGFR adapter protein"
FT /id="PRO_0000454710"
FT DOMAIN 286..379
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 18..94
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 109..154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..194
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 372..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..42
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..91
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..194
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..163
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_061376"
SQ SEQUENCE 421 AA; 46099 MW; 67729D2C824DD3F0 CRC64;
MIMQDIRLRL EPQHSKATFI SSSSASSSSS QTAETTLIET AEKSPASEAA AGTVTTTSPQ
HFFHHHHPPA HPHPPRQQPH PHSHSHPHPH PQLQRRPVEQ LHLLHSHHDV QELSGQEHPH
PQPGSHPHPH HLRSPSSEED NSPTEMNNCR RLVDKPPLVK RLTMGIGLLR GTEDSRPLMH
STCGSSLTSG SGCGSTQTIS DGYVNEAICE PDKYVASKFG DSCRQSLSAL ESATQRLQVE
LPAASKKYLR ETCSANSSPK LFPGHSALRL DNLSLAEQQE LKGAAWFQAG IPREISLEAL
SRQSPGAFLV RQSSTKPGCF ALSLRVPPPS PRVAHYLILR TQRGYKIKGF TKEFSSLKAL
ITHHSVMPEL LPVPLTLPRP PSTRSQRSQG AYAGGTGNGG ADFEMYGSLN DFRKMMADLN
V
