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Protein

Epidermal growth factor receptor

Gene

Egfr

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Binds to four ligands: Spitz, Gurken, Vein and Argos, which is an antagonist. Transduces the signal through the ras-raf-MAPK pathway. Involved in a myriad of developmental decisions. Critical for the proliferation of imaginal tissues, and for the determination of both the antero-posterior and dorso-ventral polarities of the oocyte. In the embryo, plays a role in the establishment of ventral cell fates, maintenance of amnioserosa and ventral neuroectodermal cells, germ band retraction, cell fate specification in the central nervous system and production of cuticle. Required for embryonic epithelial tissue repair.1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei971ATPPROSITE-ProRule annotation1
Active sitei1063Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi944 – 952ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • epidermal growth factor-activated receptor activity Source: FlyBase
  • identical protein binding Source: IntAct
  • protein tyrosine kinase activity Source: FlyBase
  • transmembrane signaling receptor activity Source: FlyBase

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 1994
ReactomeiR-DME-1251985 Nuclear signaling by ERBB4
R-DME-1253288 Downregulation of ERBB4 signaling
R-DME-1358803 Downregulation of ERBB2:ERBB3 signaling
R-DME-179812 GRB2 events in EGFR signaling
R-DME-180292 GAB1 signalosome
R-DME-180336 SHC1 events in EGFR signaling
R-DME-182971 EGFR downregulation
R-DME-2179392 EGFR Transactivation by Gastrin
R-DME-416572 Sema4D induced cell migration and growth-cone collapse
R-DME-445144 Signal transduction by L1
R-DME-5673001 RAF/MAP kinase cascade
R-DME-8856825 Cargo recognition for clathrin-mediated endocytosis
R-DME-8856828 Clathrin-mediated endocytosis
R-DME-8863795 Downregulation of ERBB2 signaling
SignaLinkiP04412

Names & Taxonomyi

Protein namesi
Recommended name:
Epidermal growth factor receptor (EC:2.7.10.1)
Short name:
Egfr
Alternative name(s):
Drosophila relative of ERBB
Gurken receptor
Protein torpedo
Gene namesi
Name:Egfr
Synonyms:c-erbB, DER, top
ORF Names:CG10079
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraHolometabolaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2R

Organism-specific databases

FlyBaseiFBgn0003731 Egfr

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini31 – 868ExtracellularSequence analysisAdd BLAST838
Transmembranei869 – 889HelicalSequence analysisAdd BLAST21
Topological domaini890 – 1426CytoplasmicSequence analysisAdd BLAST537

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Disruption phenotypei

Embryonic wound healing defects.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi793C → R in EGFR-ELP-1. 1
Mutagenesisi936A → T in EGFR-ELP-B1 and EGFR-ELP-B1RB1. 1
Mutagenesisi1058R → Q in EGFR-ELP-B1RB1. 1
Mutagenesisi1135T → I in EGFR-2W74. 1
Mutagenesisi1156G → S in EGFR-2C82. 1
Mutagenesisi1162P → L in EGFR-1F26. 1
Mutagenesisi1166S → L in EGFR-2L65. 1
Mutagenesisi1210 – 1216DKFTRLP → EKVHPAA in EGFR-2X51. 7

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
ChainiPRO_000001667631 – 1426Epidermal growth factor receptorAdd BLAST1396

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi128N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi241N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi419N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi443N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi482N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi569N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi599N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi617N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi816N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi823N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi828N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei902Phosphothreonine; by PKCBy similarity1
Modified residuei1310Phosphotyrosine; by autocatalysisBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP04412
PRIDEiP04412

Expressioni

Tissue specificityi

Ubiquitously expressed in embryos. In larvae, uniform expression is seen in wing disks, genital disk, anlagen of testis and ovary, and brain cortex. In eye-antenna disk, highest expression is anterior to morphogenetic furrow, levels remain high in photoreceptor precursor cells. This pattern is reversed in posterior eye disk. In adults expression is high in brain cortex and thoracic and abdominal ganglia.1 Publication

Gene expression databases

BgeeiFBgn0003731 Expressed in 66 organ(s), highest expression level in capitellum (Drosophila)
ExpressionAtlasiP04412 baseline and differential
GenevisibleiP04412 DM

Interactioni

Subunit structurei

Interacts (when phosphorylated on tyrosine residues) with Vav (via SH2 domain).1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi63083, 154 interactors
DIPiDIP-17316N
IntActiP04412, 5 interactors
MINTiP04412
STRINGi7227.FBpp0071571

Structurei

Secondary structure

11426
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP04412
SMRiP04412
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04412

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini938 – 1198Protein kinasePROSITE-ProRule annotationAdd BLAST261

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1025 Eukaryota
ENOG410XNSR LUCA
InParanoidiP04412
KOiK04361
OrthoDBiEOG091G00U7
PhylomeDBiP04412

Family and domain databases

CDDicd00064 FU, 7 hits
Gene3Di3.80.20.20, 2 hits
InterProiView protein in InterPro
IPR006211 Furin-like_Cys-rich_dom
IPR006212 Furin_repeat
IPR032778 GF_recep_IV
IPR009030 Growth_fac_rcpt_cys_sf
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR000494 Rcpt_L-dom
IPR036941 Rcpt_L-dom_sf
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016245 Tyr_kinase_EGF/ERB/XmrK_rcpt
PfamiView protein in Pfam
PF00757 Furin-like, 1 hit
PF14843 GF_recep_IV, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PF01030 Recep_L_domain, 2 hits
PIRSFiPIRSF000619 TyrPK_EGF-R, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00261 FU, 7 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 3 hits
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.iShow all

Isoform Type I (identifier: P04412-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MLLRRRNGPC PFPLLLLLLA HCICIWPASA ARDRYARQNN RQRHQDIDRD
60 70 80 90 100
RDRDRFLYRS SSAQNRQRGG ANFALGLGAN GVTIPTSLED KNKNEFVKGK
110 120 130 140 150
ICIGTKSRLS VPSNKEHHYR NLRDRYTNCT YVDGNLKLTW LPNENLDLSF
160 170 180 190 200
LDNIREVTGY ILISHVDVKK VVFPKLQIIR GRTLFSLSVE EEKYALFVTY
210 220 230 240 250
SKMYTLEIPD LRDVLNGQVG FHNNYNLCHM RTIQWSEIVS NGTDAYYNYD
260 270 280 290 300
FTAPERECPK CHESCTHGCW GEGPKNCQKF SKLTCSPQCA GGRCYGPKPR
310 320 330 340 350
ECCHLFCAGG CTGPTQKDCI ACKNFFDEAV SKEECPPMRK YNPTTYVLET
360 370 380 390 400
NPEGKYAYGA TCVKECPGHL LRDNGACVRS CPQDKMDKGG ECVPCNGPCP
410 420 430 440 450
KTCPGVTVLH AGNIDSFRNC TVIDGNIRIL DQTFSGFQDV YANYTMGPRY
460 470 480 490 500
IPLDPERREV FSTVKEITGY LNIEGTHPQF RNLSYFRNLE TIHGRQLMES
510 520 530 540 550
MFAALAIVKS SLYSLEMRNL KQISSGSVVI QHNRDLCYVS NIRWPAIQKE
560 570 580 590 600
PEQKVWVNEN LRADLCEKNG TICSDQCNED GCWGAGTDQC LTCKNFNFNG
610 620 630 640 650
TCIADCGYIS NAYKFDNRTC KICHPECRTC NGAGADHCQE CVHVRDGQHC
660 670 680 690 700
VSECPKNKYN DRGVCRECHA TCDGCTGPKD TIGIGACTTC NLAIINNDAT
710 720 730 740 750
VKRCLLKDDK CPDGYFWEYV HPQEQGSLKP LAGRAVCRKC HPLCELCTNY
760 770 780 790 800
GYHEQVCSKC THYKRREQCE TECPADHYTD EEQRECFQRH PECNGCTGPG
810 820 830 840 850
ADDCKSCRNF KLFDANETGP YVNSTMFNCT SKCPLEMRHV NYQYTAIGPY
860 870 880 890 900
CAASPPRSSK ITANLDVNMI FIITGAVLVP TICILCVVTY ICRQKQKAKK
910 920 930 940 950
ETVKMTMALS GCEDSEPLRP SNIGANLCKL RIVKDAELRK GGVLGMGAFG
960 970 980 990 1000
RVYKGVWVPE GENVKIPVAI KELLKSTGAE SSEEFLREAY IMASEEHVNL
1010 1020 1030 1040 1050
LKLLAVCMSS QMMLITQLMP LGCLLDYVRN NRDKIGSKAL LNWSTQIAKG
1060 1070 1080 1090 1100
MSYLEEKRLV HRDLAARNVL VQTPSLVKIT DFGLAKLLSS DSNEYKAAGG
1110 1120 1130 1140 1150
KMPIKWLALE CIRNRVFTSK SDVWAFGVTI WELLTFGQRP HENIPAKDIP
1160 1170 1180 1190 1200
DLIEVGLKLE QPEICSLDIY CTLLSCWHLD AAMRPTFKQL TTVFAEFARD
1210 1220 1230 1240 1250
PGRYLAIPGD KFTRLPAYTS QDEKDLIRKL APTTDGSEAI AKPDDYLQPK
1260 1270 1280 1290 1300
AAPGPSHRTD CTDEMPKLNR YCKDPSNKNS STGDDERDSS AREVGVGNLR
1310 1320 1330 1340 1350
LDLPVDEDDY LMPTCQPGPN NNNNMNNPNQ NNMAAVGVAA GYMDLIGVPV
1360 1370 1380 1390 1400
SVDNPEYLLN AQTLGVGESP IPTQTIGIPV MGGPGTMEVK VPMPGSEPTS
1410 1420
SDHEYYNDTQ RELQPLHRNR NTETRV
Length:1,426
Mass (Da):159,718
Last modified:December 15, 1998 - v3
Checksum:i4D424C3C99DA4AF4
GO
Isoform Type II (identifier: P04412-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-101: MLLRRRNGPC...NKNEFVKGKI → MMIISMWMSI...GYVDNGNMKV

Show »
Length:1,377
Mass (Da):153,700
Checksum:iAEA869BD7849A0D5
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q8MLW0Q8MLW0_DROME
Receptor protein-tyrosine kinase
Egfr CG10079, Dmel_CG10079
1,377Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti137K → E (PubMed:9882502).Curated1
Sequence conflicti137K → E (PubMed:10731132).Curated1
Sequence conflicti329 – 331AVS → GVC (PubMed:9882502).Curated3
Sequence conflicti329 – 331AVS → GVC (PubMed:10731132).Curated3
Sequence conflicti458R → L (PubMed:9882502).Curated1
Sequence conflicti458R → L (PubMed:10731132).Curated1
Sequence conflicti789R → C (PubMed:9882502).Curated1
Sequence conflicti789R → C (PubMed:10731132).Curated1
Sequence conflicti959P → A in CAA26157 (PubMed:2983232).Curated1
Sequence conflicti995E → V (PubMed:9882502).Curated1
Sequence conflicti995E → V (PubMed:10731132).Curated1
Sequence conflicti1072 – 1080QTPSLVKIT → RLLAGEDH (PubMed:2982499).Curated9
Sequence conflicti1072 – 1080QTPSLVKIT → RLLAGEDH (PubMed:3093080).Curated9
Sequence conflicti1072 – 1080QTPSLVKIT → RLLAGEDH (PubMed:9731193).Curated9
Sequence conflicti1097 – 1098AA → I in CAA05747 (PubMed:9731193).Curated2
Sequence conflicti1118T → R in CAA05747 (PubMed:9731193).Curated1
Sequence conflicti1242K → E (PubMed:9882502).Curated1
Sequence conflicti1242K → E (PubMed:10731132).Curated1
Sequence conflicti1265M → I (PubMed:9882502).Curated1
Sequence conflicti1265M → I (PubMed:10731132).Curated1
Sequence conflicti1287R → T (PubMed:9882502).Curated1
Sequence conflicti1287R → T (PubMed:10731132).Curated1
Sequence conflicti1325M → I in AAF46732 (PubMed:10731132).Curated1
Sequence conflicti1383G → V (PubMed:9882502).Curated1
Sequence conflicti1383G → V (PubMed:10731132).Curated1
Sequence conflicti1412 – 1426ELQPL…TETRV → SCSHASKPQHGDEGVGSSRV GAIANEEGESCQVPLEAMRY AFAGCYLR (PubMed:2982499).CuratedAdd BLAST15
Sequence conflicti1412 – 1426ELQPL…TETRV → SCSHASKPQHGDEGVGSSRV GAIANEEGESCQVPLEAMRY AFAGCYLR (PubMed:3093080).CuratedAdd BLAST15

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0028971 – 101MLLRR…VKGKI → MMIISMWMSISRGLWDSSSI LSVLLILACMASITTSSSVS NAGYVDNGNMKV in isoform Type II. CuratedAdd BLAST101

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF052754, AF052753 Genomic DNA Translation: AAC08536.1
AF052754, AF052752 Genomic DNA Translation: AAC08535.1
K03054 Genomic DNA Translation: AAA51462.1
K03417 mRNA Translation: AAA51460.1
K03416 mRNA Translation: AAA50965.1
AF109077 Genomic DNA Translation: AAD26134.1
AF109078, AF109082 Genomic DNA Translation: AAD26132.1
AF109078, AF109084 Genomic DNA Translation: AAD26133.1
AF109079, AF109081 Genomic DNA Translation: AAD26130.1
AF109079, AF109083 Genomic DNA Translation: AAD26131.1
AF109080 Genomic DNA Translation: AAD26135.1
AE013599 Genomic DNA Translation: AAF46732.1
X02293 Genomic DNA Translation: CAA26157.1
AJ002912 Genomic DNA Translation: CAA05747.1
X78920 Genomic DNA Translation: CAA55523.1
X78918 Genomic DNA Translation: CAA55521.1
X78919 Genomic DNA Translation: CAA55522.1
PIRiA00640 GQFFE
RefSeqiNP_476759.1, NM_057411.4

Genome annotation databases

GeneIDi37455
KEGGidme:Dmel_CG10079

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiEGFR_DROME
AccessioniPrimary (citable) accession number: P04412
Secondary accession number(s): O18370
, O61601, P81868, Q9W2G0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: December 15, 1998
Last modified: September 12, 2018
This is version 210 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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