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Protein

Epidermal growth factor receptor

Gene

EGFR

Organism
Macaca mulatta (Rhesus macaque)
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. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Plays a role in enhancing learning and memory performance.By similarity

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 like PTPRJ and PTPRK constitute immediate regulatory mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR endocytosis and activity. Moreover, inducible feedback inhibitors including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative regulatory mechanisms for the EGFR signaling.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei745ATPPROSITE-ProRule annotation1
Active sitei837Proton acceptorPROSITE-ProRule annotation1
Binding sitei855ATPPROSITE-ProRule annotation1
Sitei1016Important for interaction with PIK3C2BBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi718 – 726ATPPROSITE-ProRule annotation9
Nucleotide bindingi790 – 791ATPPROSITE-ProRule annotation2

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Epidermal growth factor receptor (EC:2.7.10.1)
Gene namesi
Name:EGFR
OrganismiMacaca mulatta (Rhesus macaque)
Taxonomic identifieri9544 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca
Proteomesi
  • UP000006718 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 645ExtracellularSequence analysisAdd BLAST621
Transmembranei646 – 668HelicalSequence analysisAdd BLAST23
Topological domaini669 – 1210CytoplasmicSequence analysisAdd BLAST542

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000016025425 – 1210Epidermal growth factor receptorAdd BLAST1186

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi31 ↔ 58By similarity
Glycosylationi128N-linked (GlcNAc...)By similarity1
Disulfide bondi157 ↔ 187By similarity
Glycosylationi175N-linked (GlcNAc...)By similarity1
Disulfide bondi190 ↔ 199By similarity
Disulfide bondi194 ↔ 207By similarity
Glycosylationi196N-linked (GlcNAc...)By similarity1
Disulfide bondi215 ↔ 223By similarity
Disulfide bondi219 ↔ 231By similarity
Modified residuei229PhosphoserineBy similarity1
Disulfide bondi232 ↔ 240By similarity
Disulfide bondi236 ↔ 248By similarity
Disulfide bondi251 ↔ 260By similarity
Disulfide bondi264 ↔ 291By similarity
Disulfide bondi295 ↔ 307By similarity
Disulfide bondi311 ↔ 326By similarity
Disulfide bondi329 ↔ 333By similarity
Disulfide bondi337 ↔ 362By similarity
Glycosylationi352N-linked (GlcNAc...)By similarity1
Glycosylationi361N-linked (GlcNAc...)By similarity1
Glycosylationi413N-linked (GlcNAc...)By similarity1
Glycosylationi444N-linked (GlcNAc...)By similarity1
Disulfide bondi470 ↔ 499By similarity
Disulfide bondi506 ↔ 515By similarity
Disulfide bondi510 ↔ 523By similarity
Disulfide bondi526 ↔ 535By similarity
Glycosylationi528N-linked (GlcNAc...)By similarity1
Disulfide bondi539 ↔ 555By similarity
Disulfide bondi558 ↔ 571By similarity
Disulfide bondi562 ↔ 579By similarity
Glycosylationi568N-linked (GlcNAc...)By similarity1
Disulfide bondi582 ↔ 591By similarity
Disulfide bondi595 ↔ 617By similarity
Glycosylationi603N-linked (GlcNAc...)By similarity1
Disulfide bondi620 ↔ 628By similarity
Disulfide bondi624 ↔ 636By similarity
Modified residuei678Phosphothreonine; by PKC and PKD/PRKD1By similarity1
Modified residuei693Phosphothreonine; by PKD/PRKD1By similarity1
Modified residuei695PhosphoserineBy similarity1
Cross-linki716Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki737Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki754Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki867Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki929Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki970Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei991PhosphoserineBy similarity1
Modified residuei995PhosphoserineBy similarity1
Modified residuei998Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1016Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1026PhosphoserineBy similarity1
Modified residuei1039PhosphoserineBy similarity1
Modified residuei1041PhosphothreonineBy similarity1
Modified residuei1042PhosphoserineBy similarity1
Modified residuei1064PhosphoserineBy similarity1
Modified residuei1070PhosphoserineBy similarity1
Modified residuei1071PhosphoserineBy similarity1
Modified residuei1081PhosphoserineBy similarity1
Modified residuei1092Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1110Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1166PhosphoserineBy similarity1
Modified residuei1172Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1197Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1199Omega-N-methylarginine; alternateBy similarity1
Modified residuei1199Omega-N-methylated arginine; alternateBy similarity1

Post-translational modificationi

Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occurs. Deubiquitinated by OTUD7B, preventing degradation. Ubiquitinated by RNF115 and RNF126.By similarity
Phosphorylated. Autophosphorylates. Dephosphorylated by PTPN1 and PTPN2 (By similarity).By similarity
Methylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP55245.

Expressioni

Tissue specificityi

Hypothalamus.

Developmental stagei

Levels in the medial basal hypothalamus and preoptic area are elevated during neonatal life (1 week-6 months), decrease during juvenile development (8-18 months) and markedly increase during the expected time of puberty (30-36 months).

Gene expression databases

BgeeiENSMMUG00000022394.

Interactioni

Subunit structurei

Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation. Heterodimer with ERBB2. Interacts with ERRFI1; inhibits dimerization of the kinase domain and autophosphorylation. Part of a complex with ERBB2 and either PIK3C2A or PIK3C2B. Interacts with GRB2; an adapter protein coupling the receptor to downstream signaling pathways. Interacts with GAB2; involved in signaling downstream of EGFR. Interacts with STAT3; mediates EGFR downstream signaling in cell proliferation. Interacts with RIPK1; involved in NF-kappa-B activation. Interacts (autophosphorylated) with CBL, CBLB and CBLC; involved in EGFR ubiquitination and regulation. Interacts with SOCS5; regulates EGFR degradation through TCEB1- and TCEB2-mediated ubiquitination and proteasomal degradation. Interacts with PRMT5; methylates EGFR and enhances interaction with PTPN6. Interacts (phosphorylated) with PTPN6; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with COPG1; essential for regulation of EGF-dependent nuclear transport of EGFR by retrograde trafficking from the Golgi to the ER. Interacts with TNK2; this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts with PCNA; positively regulates PCNA. Interacts with PELP1. Interacts with MUC1. Interacts with AP2M1. Interacts with FER. May interact with EPS8; mediates EPS8 phosphorylation. Interacts (via SH2 domains) with GRB2, NCK1 and NCK2. Interacts with ATX2. Interacts with GAREM1. Interacts (ubiquitinated) with ANKRD13A/B/D; the interaction is direct and may regulate EGFR internalization after EGF stimulation. Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts (via C-terminal cytoplasmic kinase domain) with ZPR1 (via zinc fingers). Interacts with RNF115 and RNF126. Interacts with GPRC5A (via its transmembrane domain). Interacts with FAM83B; positively regulates EGFR inducing its autophospharylation in absence of stimulation by EGF (By similarity).By similarity

Protein-protein interaction databases

STRINGi9544.ENSMMUP00000029471.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati75 – 300ApproximateAdd BLAST226
Repeati390 – 600ApproximateAdd BLAST211
Domaini712 – 979Protein kinasePROSITE-ProRule annotationAdd BLAST268

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni688 – 704Important for dimerization, phosphorylation and activationBy similarityAdd BLAST17

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

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1025. Eukaryota.
ENOG410XNSR. LUCA.
HOGENOMiHOG000230982.
InParanoidiP55245.
KOiK04361.
TreeFamiTF106002.

Family and domain databases

Gene3Di3.80.20.20. 2 hits.
InterProiIPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR032778. GF_recep_IV.
IPR009030. Growth_fac_rcpt_.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000494. Rcpt_L-dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
[Graphical view]
PfamiPF00757. Furin-like. 1 hit.
PF14843. GF_recep_IV. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFiPIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00261. FU. 4 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P55245-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS
60 70 80 90 100
LQRMFNNCEV VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP
110 120 130 140 150
LENLQIIRGN MYYENSYALA VLSNYDANKT GLKELPMRNL QEILHGAVRF
160 170 180 190 200
SNNPALCNVE SIQWRDIVSS EFLSNMSMDF QNHLGSCQKC DPSCPNGSCW
210 220 230 240 250
GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC TGPRESDCLV
260 270 280 290 300
CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV
310 320 330 340 350
VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDTLS
360 370 380 390 400
INATNIKHFK NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE
410 420 430 440 450
ITGFLLIQAW PENRTDLHAF ENLEIIRGRT KQHGQFSLAV VSLNITSLGL
460 470 480 490 500
RSLKEISDGD VIISGNKNLC YANTINWKKL FGTSSQKTKI ISNRGENSCK
510 520 530 540 550
ATGQVCHALC SPEGCWGPEP RDCVSCQNVS RGRECVDKCN VLEGEPREFV
560 570 580 590 600
ENSECIQCHP ECLPQVMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM
610 620 630 640 650
GENNTLVWKY ADAGHVCHLC HPNCTYGCTG PGLEGCARNG PKIPSIATGM
660 670 680 690 700
VGALLLLLVV ALGIGLFMRR RHIVRKRTLR RLLQERELVE PLTPSGEAPN
710 720 730 740 750
QALLRILKET EFKKIKVLGS GAFGTVYKGL WIPEGEKVKI PVAIKELREA
760 770 780 790 800
TSPKANKEIL DEAYVMASVD NPHVCRLLGI CLTSTVQLIT QLMPFGCLLD
810 820 830 840 850
YVREHKDNIG SQYLLNWCVQ IAKGMNYLED RRLVHRDLAA RNVLVKTPQH
860 870 880 890 900
VKITDFGLAK LLGAEEKEYH AEGGKVPIKW MALESILHRI YTHQSDVWSY
910 920 930 940 950
GVTVWELMTF GSKPYDGIPA SEISSILEKG ERLPQPPICT IDVYMIMVKC
960 970 980 990 1000
WMIDADSRPK FRELIIEFSK MARDPQRYLV IQGDERMHLP SPTDSNFYRA
1010 1020 1030 1040 1050
LMDEEDMDDV VDADEYLIPQ QGFFSSPSTS RTPLLSSLSA TSNNSTVACI
1060 1070 1080 1090 1100
DRNGLQSCPI KEDSFLQRYS SDPTGALTED SIDDTFLPVP EYINQSVPKR
1110 1120 1130 1140 1150
PAGSVQNPVY HNQPLNPAPS RDPHYQDPHS TAVGNPEYLN TVQPTCVNST
1160 1170 1180 1190 1200
FDSPAHWAQK GSHQISLDNP DYQQDFFPKE AKPNGIFKGS TAENAEYLRV
1210
APQSSEFIGA
Length:1,210
Mass (Da):134,350
Last modified:January 22, 2014 - v2
Checksum:iE114E9CEE96D64CC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti541V → I in EHH17303 (PubMed:22002653).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JH286850 Genomic DNA. No translation available.
CM001255 Genomic DNA. Translation: EHH17303.1.
JU327815 mRNA. Translation: AFE71571.1.
S75916 mRNA. Translation: AAB33095.1.
PIRiI78540.
RefSeqiXP_014988922.1. XM_015133436.1.
UniGeneiMmu.3397.

Genome annotation databases

GeneIDi613027.
KEGGimcc:613027.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
JH286850 Genomic DNA. No translation available.
CM001255 Genomic DNA. Translation: EHH17303.1.
JU327815 mRNA. Translation: AFE71571.1.
S75916 mRNA. Translation: AAB33095.1.
PIRiI78540.
RefSeqiXP_014988922.1. XM_015133436.1.
UniGeneiMmu.3397.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9544.ENSMMUP00000029471.

Proteomic databases

PRIDEiP55245.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi613027.
KEGGimcc:613027.

Organism-specific databases

CTDi1956.

Phylogenomic databases

eggNOGiKOG1025. Eukaryota.
ENOG410XNSR. LUCA.
HOGENOMiHOG000230982.
InParanoidiP55245.
KOiK04361.
TreeFamiTF106002.

Gene expression databases

BgeeiENSMMUG00000022394.

Family and domain databases

Gene3Di3.80.20.20. 2 hits.
InterProiIPR006211. Furin-like_Cys-rich_dom.
IPR006212. Furin_repeat.
IPR032778. GF_recep_IV.
IPR009030. Growth_fac_rcpt_.
IPR011009. Kinase-like_dom.
IPR032675. L_dom-like.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR000494. Rcpt_L-dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
[Graphical view]
PfamiPF00757. Furin-like. 1 hit.
PF14843. GF_recep_IV. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF01030. Recep_L_domain. 2 hits.
[Graphical view]
PIRSFiPIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00261. FU. 4 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEGFR_MACMU
AccessioniPrimary (citable) accession number: P55245
Secondary accession number(s): F6YXS7, G7ML99, H9FAB2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 22, 2014
Last modified: November 2, 2016
This is version 137 of the entry and version 2 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

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 one 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.