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Protein

Epidermal growth factor receptor

Gene

EGFR

Organism
Gallus gallus (Chicken)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade.

Catalytic activityi

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

Enzyme regulationi

Endocytosis and inhibition of the activated EGFR by phosphatases constitute immediate regulatory mechanisms. Moreover, inducible feedback inhibitors may constitute alternative regulatory mechanisms for the EGFR signaling.

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein tyrosine kinase activity Source: UniProtKB
  3. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. cellular response to epidermal growth factor stimulus Source: UniProtKB
  2. epidermal growth factor receptor signaling pathway Source: UniProtKB
  3. learning or memory Source: UniProtKB
  4. peptidyl-tyrosine phosphorylation Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_276949. EGFR interacts with phospholipase C-gamma.
REACT_284939. PIP3 activates AKT signaling.
REACT_286650. Inhibition of Signaling by Overexpressed EGFR.
REACT_287528. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.
REACT_297620. SHC1 events in ERBB2 signaling.
REACT_300902. SHC1 events in EGFR signaling.
REACT_303024. GRB2 events in EGFR signaling.
REACT_303474. EGFR Transactivation by Gastrin.
REACT_305915. PI3K events in ERBB2 signaling.
REACT_322031. GAB1 signalosome.
REACT_328052. Signaling by EGFR.
REACT_329474. GRB2 events in ERBB2 signaling.
REACT_332376. EGFR downregulation.
REACT_334887. Signaling by ERBB4.
REACT_343900. Constitutive PI3K/AKT Signaling in Cancer.
REACT_351792. PLCG1 events in ERBB2 signaling.
REACT_352815. Constitutive Signaling by EGFRvIII.
REACT_354408. Signaling by ERBB2.

Names & Taxonomyi

Protein namesi
Recommended name:
Epidermal growth factor receptor (EC:2.7.10.1)
Short name:
CER
Gene namesi
Name:EGFR
OrganismiGallus gallus (Chicken)
Taxonomic identifieri9031 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiArchelosauriaArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalloanseraeGalliformesPhasianidaePhasianinaeGallus
ProteomesiUP000000539 Componenti: Unplaced

Subcellular locationi

  1. Cell membrane; Single-pass type I membrane protein
  2. Endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein By similarity
  3. Golgi apparatus membrane By similarity; Single-pass type I membrane protein By similarity
  4. Nucleus membrane By similarity; Single-pass type I membrane protein By similarity
  5. Endosome
  6. Endosome membrane
  7. Nucleus By similarity

  8. Note: In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER. Endocytosed upon activation by ligand (By similarity).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini31 – 654624ExtracellularSequence AnalysisAdd
BLAST
Transmembranei655 – 66713HelicalSequence AnalysisAdd
BLAST
Topological domaini668 – ›703›36CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  2. endosome membrane Source: UniProtKB-SubCell
  3. Golgi membrane Source: UniProtKB-SubCell
  4. integral component of membrane Source: UniProtKB-KW
  5. nuclear membrane Source: UniProtKB-SubCell
  6. nucleus Source: UniProtKB
  7. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3030Add
BLAST
Chaini31 – ›703›673Epidermal growth factor receptorPRO_0000016667Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi134 – 1341N-linked (GlcNAc...)Sequence Analysis
Glycosylationi190 – 1901N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi197 ↔ 206By similarity
Glycosylationi200 – 2001N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi201 ↔ 214By similarity
Disulfide bondi222 ↔ 230By similarity
Disulfide bondi226 ↔ 238By similarity
Disulfide bondi239 ↔ 247By similarity
Disulfide bondi243 ↔ 255By similarity
Disulfide bondi258 ↔ 267By similarity
Disulfide bondi271 ↔ 298By similarity
Disulfide bondi302 ↔ 314By similarity
Disulfide bondi318 ↔ 333By similarity
Disulfide bondi336 ↔ 340By similarity
Glycosylationi359 – 3591N-linked (GlcNAc...)Sequence Analysis
Glycosylationi368 – 3681N-linked (GlcNAc...)Sequence Analysis
Glycosylationi420 – 4201N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi513 ↔ 522By similarity
Disulfide bondi517 ↔ 530By similarity
Disulfide bondi533 ↔ 542By similarity
Disulfide bondi546 ↔ 562By similarity
Disulfide bondi565 ↔ 581By similarity
Disulfide bondi569 ↔ 589By similarity
Glycosylationi573 – 5731N-linked (GlcNAc...)Sequence Analysis
Glycosylationi578 – 5781N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi592 ↔ 601By similarity
Disulfide bondi605 ↔ 627By similarity
Glycosylationi613 – 6131N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi630 ↔ 638By similarity
Glycosylationi633 – 6331N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi634 ↔ 646By similarity
Glycosylationi648 – 6481N-linked (GlcNAc...)Sequence Analysis
Modified residuei687 – 6871PhosphothreonineBy similarity
Modified residuei702 – 7021PhosphothreonineBy similarity

Post-translational modificationi

Phosphorylated. Autophosphorylates (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP13387.

Expressioni

Gene expression databases

ExpressionAtlasiP13387. baseline and differential.

Interactioni

Subunit structurei

Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation.By similarity

Protein-protein interaction databases

STRINGi9031.ENSGALP00000020165.

Structurei

3D structure databases

ProteinModelPortaliP13387.
SMRiP13387. Positions 31-530, 678-703.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000230982.
HOVERGENiHBG000490.
InParanoidiP13387.
KOiK04361.
PhylomeDBiP13387.

Family and domain databases

Gene3Di3.80.20.20. 2 hits.
InterProiIPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR000494. Rcpt_L-dom.
[Graphical view]
PfamiPF00757. Furin-like. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
SMARTiSM00261. FU. 5 hits.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 2 hits.

Sequencei

Sequence statusi: Fragment.

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

P13387-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGVRSPLSAS GPRGAAVLVL LLLGVALCSA VEEKKVCQGT NNKLTQLGHV
60 70 80 90 100
EDHFTSLQRM YNNCEVVLSN LEITYVEHNR DLTFLKTIQE VAGYVLIALN
110 120 130 140 150
MVDVIPLENL QIIRGNVLYD NSFALAVLSN YHMNKTQGLR ELPMKRLSEI
160 170 180 190 200
LNGGVKISNN PKLCNMDTVL WNDIIDTSRK PLTVLDFASN LSSCPKCHPN
210 220 230 240 250
CTEDHCWGAG EQNCQTLTKV ICAQQCSGRC RGKVPSDCCH NQCAAGCTGP
260 270 280 290 300
RESDCLACRK FRDDATCKDT CPPLVLYNPT TYQMDVNPEG KYSFGATCVR
310 320 330 340 350
ECPHNYVVTD HGSCVRSCNT DTYEVEENGV RKCKKCDGLC SKVCNGIGIG
360 370 380 390 400
ELKGILSINA TNIDSFKNCT KINGDVSILP VAFLGDAFTK TLPLDPKKLD
410 420 430 440 450
VFRTVKEISG FLLIQAWPDN ATDLYAFENL EIIRGRTKQH GQYSLAVVNL
460 470 480 490 500
KIQSLGLRSL KEISDGDIAI MKNKNLCYAD TMNWRSLFAT QSQKTKIIQN
510 520 530 540 550
RNKNDCTADR HVCDPLCSDV GCWGPGPFHC FSCRFFSRQK ECVKQCNILQ
560 570 580 590 600
GEPREFERDS KCLPCHSECL VQNSTAYNTT CSGPGPDHCM KCAHFIDGPH
610 620 630 640 650
CVKACPAGVL GENDTLVWKY ADANAVCQLC HPNCTRGCKG PGLEGCPNGS
660 670 680 690 700
KTPSIAAGVV GGLLCLVVVG LGIGLYLRRR HIVRKRTLRR LLQERELVEP

LTP
Length:703
Mass (Da):77,427
Last modified:January 1, 1990 - v1
Checksum:iAFF2DE11B735A690
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei703 – 7031

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20386 mRNA. Translation: AAA48760.1.
RefSeqiNP_990828.2. NM_205497.2.
UniGeneiGga.35024.

Genome annotation databases

GeneIDi396494.
KEGGigga:396494.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20386 mRNA. Translation: AAA48760.1.
RefSeqiNP_990828.2. NM_205497.2.
UniGeneiGga.35024.

3D structure databases

ProteinModelPortaliP13387.
SMRiP13387. Positions 31-530, 678-703.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9031.ENSGALP00000020165.

Proteomic databases

PaxDbiP13387.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi396494.
KEGGigga:396494.

Organism-specific databases

CTDi1956.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000230982.
HOVERGENiHBG000490.
InParanoidiP13387.
KOiK04361.
PhylomeDBiP13387.

Enzyme and pathway databases

ReactomeiREACT_276949. EGFR interacts with phospholipase C-gamma.
REACT_284939. PIP3 activates AKT signaling.
REACT_286650. Inhibition of Signaling by Overexpressed EGFR.
REACT_287528. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.
REACT_297620. SHC1 events in ERBB2 signaling.
REACT_300902. SHC1 events in EGFR signaling.
REACT_303024. GRB2 events in EGFR signaling.
REACT_303474. EGFR Transactivation by Gastrin.
REACT_305915. PI3K events in ERBB2 signaling.
REACT_322031. GAB1 signalosome.
REACT_328052. Signaling by EGFR.
REACT_329474. GRB2 events in ERBB2 signaling.
REACT_332376. EGFR downregulation.
REACT_334887. Signaling by ERBB4.
REACT_343900. Constitutive PI3K/AKT Signaling in Cancer.
REACT_351792. PLCG1 events in ERBB2 signaling.
REACT_352815. Constitutive Signaling by EGFRvIII.
REACT_354408. Signaling by ERBB2.

Miscellaneous databases

NextBioi20816533.

Gene expression databases

ExpressionAtlasiP13387. baseline and differential.

Family and domain databases

Gene3Di3.80.20.20. 2 hits.
InterProiIPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_N_dom.
IPR000494. Rcpt_L-dom.
[Graphical view]
PfamiPF00757. Furin-like. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
SMARTiSM00261. FU. 5 hits.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 2 hits.
ProtoNetiSearch...

Publicationsi

  1. "Chicken epidermal growth factor (EGF) receptor: cDNA cloning, expression in mouse cells, and differential binding of EGF and transforming growth factor alpha."
    Lax I., Johnson A., Howk R., Sap J., Bellot F., Winkler M., Ullrich A., Vennstrom B., Schlessinger J., Givol D.
    Mol. Cell. Biol. 8:1970-1978(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiEGFR_CHICK
AccessioniPrimary (citable) accession number: P13387
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: April 29, 2015
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.