P55245 (EGFR_MACMU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Epidermal growth factor receptor
EC=2.7.10.1

Gene names

Name:

EGFR

Organism

Macaca mulatta (Rhesus macaque) [Reference proteome]

Taxonomic identifier

9544 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Cercopithecoidea › Cercopithecidae › Cercopithecinae › Macaca

Protein attributes

Sequence length	85 AA.
Sequence status	Fragment.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	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.
Subunit structure	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; 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 By similarity. Interacts with ATX2 By similarity. Interacts with GAREM By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Endoplasmic reticulum membrane; Single-pass type I membrane protein By similarity. Golgi apparatus membrane; Single-pass type I membrane protein By similarity. Nucleus membrane; Single-pass type I membrane protein By similarity. Endosome. Endosome membrane By similarity. Note: In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER. Endocytosed upon activation by ligand By similarity.
Tissue specificity	Hypothalamus.
Developmental stage	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).
Post-translational modification	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 occur. Deubiquitinated by OTUD7B, preventing degradation By similarity. Phosphorylated. Autophosphorylates By similarity. Methylated By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Endosome Golgi apparatus Membrane Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell morphogenesis Inferred from electronic annotation. Source: Compara cell proliferation Inferred from electronic annotation. Source: Compara cell-cell adhesion Inferred from electronic annotation. Source: Compara cerebral cortex cell migration Inferred from electronic annotation. Source: Compara digestive tract morphogenesis Inferred from electronic annotation. Source: Compara embryonic placenta development Inferred from electronic annotation. Source: Compara hair follicle development Inferred from electronic annotation. Source: Compara morphogenesis of an epithelial fold Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of protein catabolic process Inferred from electronic annotation. Source: Compara positive regulation of DNA repair Inferred from electronic annotation. Source: Compara positive regulation of DNA replication Inferred from electronic annotation. Source: Compara positive regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara positive regulation of catenin import into nucleus Inferred from electronic annotation. Source: Compara positive regulation of cell migration Inferred from electronic annotation. Source: Compara positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of fibroblast proliferation Inferred from electronic annotation. Source: Compara positive regulation of nitric oxide biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of nitric-oxide synthase activity Inferred from electronic annotation. Source: Compara regulation of peptidyl-tyrosine phosphorylation Inferred from electronic annotation. Source: Compara response to UV-A Inferred from electronic annotation. Source: Compara salivary gland morphogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell basolateral plasma membrane Inferred from electronic annotation. Source: Compara endocytic vesicle Inferred from electronic annotation. Source: Compara endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endosome Inferred from sequence or structural similarity. Source: UniProtKB endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane raft Inferred from electronic annotation. Source: Compara nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW epidermal growth factor-activated receptor activity Inferred from electronic annotation. Source: Compara nitric-oxide synthase regulator activity Inferred from electronic annotation. Source: Compara protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	‹1 – ›85	›85	Epidermal growth factor receptor		PRO_0000160254
Regions
	Domain	‹1 – 77	›77	Protein kinase
Amino acid modifications
	Cross-link	37		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
	Cross-link	78		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Experimental info
	Non-terminal residue	1	1
	Non-terminal residue	85	1

Sequences

	Sequence		Length	Mass (Da)
	P55245 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: D812DF47C23B3C18	FASTA	85	9,866
	10 20 30 40 50 60 HQSDVWSYGV TVWELMTFGS KPYDGIPASE ISSILEKGER LPQPPICTID VYMIMVKCWM 70 80 IDADSRPKFR ELIIEFSKMA RDPQR

References

[1]

"Developmental expression of the genes encoding transforming growth factor alpha and its receptor in the hypothalamus of female rhesus macaques." Ma Y.J., Costa M.E., Ojeda S.R. Neuroendocrinology 60:346-359(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hypothalamus.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S75916 mRNA. Translation: AAB33095.1.
PIR	I78540.
UniGene	Mmu.3397.
3D structure databases
ProteinModelPortal	P55245.
SMR	P55245. Positions 1-85.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000230982.
InParanoid	P55245.
OrthoDB	EOG44MXR6.
Gene expression databases
ArrayExpress	P55245.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. [Graphical view]
Pfam	PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. Partial match. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. Partial match. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P55245.

Entry information

Entry name

EGFR_MACMU

Accession

Primary (citable) accession number: P55245

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program