ID:EGF_HUMAN DESCRIPTION: RecName: Full=Pro-epidermal growth factor; Short=EGF; Contains: RecName: Full=Epidermal growth factor; AltName: Full=Urogastrone; Flags: Precursor; FUNCTION: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6. SUBUNIT: Interacts with EGFR and promotes EGFR dimerization. Interacts with RHBDF2 (By similarity). Interacts with RHBDF1; may retain EGF in the endoplasmic reticulum and regulates its degradation through the endoplasmic reticulum-associated degradation (ERAD). INTERACTION: P00533:EGFR; NbExp=3; IntAct=EBI-640857, EBI-297353; SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. TISSUE SPECIFICITY: Expressed in kidney, salivary gland, cerebrum and prostate. PTM: O-glycosylated with core 1-like and core 2-like glycans. It is uncertain if Ser-954 or Thr-955 is O-glycosylated. The modification here shows glycan heterogeneity: HexHexNAc (major) and Hex2HexNAc2 (minor). DISEASE: Defects in EGF are the cause of hypomagnesemia type 4 (HOMG4) [MIM:611718]; also known as renal hypomagnesemia normocalciuric. HOMG4 is a disorder characterized by massive renal hypomagnesemia and normal levels of serum calcium and calcium excretion. Clinical features include seizures, mild-to mederate psychomotor retardation, and brisk tendon reflexes. SIMILARITY: Contains 9 EGF-like domains. SIMILARITY: Contains 9 LDL-receptor class B repeats. SEQUENCE CAUTION: Sequence=AAR84237.1; Type=Erroneous gene model prediction; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/egf/"; WEB RESOURCE: Name=Wikipedia; Note=Epidermal growth factor entry; URL="http://en.wikipedia.org/wiki/Epidermal_growth_factor";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P01133
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK299306 - Homo sapiens cDNA FLJ60402 complete cds, highly similar to Pro-epidermal growth factor precursor. LP896316 - Sequence 1180 from Patent EP3253886. LP895487 - Sequence 351 from Patent EP3253886. X04571 - Human mRNA for kidney epidermal growth factor (EGF) precursor. BC113461 - Homo sapiens epidermal growth factor (beta-urogastrone), mRNA (cDNA clone MGC:142021 IMAGE:8322513), complete cds. BC093731 - Homo sapiens epidermal growth factor (beta-urogastrone), mRNA (cDNA clone MGC:120766 IMAGE:7939576), complete cds. BC143357 - Homo sapiens cDNA clone IMAGE:9051862. JD385831 - Sequence 366855 from Patent EP1572962. JD256214 - Sequence 237238 from Patent EP1572962. JD200092 - Sequence 181116 from Patent EP1572962. JD270692 - Sequence 251716 from Patent EP1572962. AK307734 - Homo sapiens cDNA, FLJ97682. AY548762 - Homo sapiens epidermal growth factor (EGF) mRNA, partial cds. JQ346088 - Homo sapiens epidermal growth factor precursor (EGF) mRNA, partial cds. JD068883 - Sequence 49907 from Patent EP1572962. JD375354 - Sequence 356378 from Patent EP1572962. JD563948 - Sequence 544972 from Patent EP1572962. JD196560 - Sequence 177584 from Patent EP1572962. JD402599 - Sequence 383623 from Patent EP1572962. JD493054 - Sequence 474078 from Patent EP1572962. JD337854 - Sequence 318878 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_keratinocytePathway - Keratinocyte Differentiation h_cblPathway - CBL mediated ligand-induced downregulation of EGF receptors h_eea1Pathway - The role of FYVE-finger proteins in vesicle transport h_egfr_smrtePathway - Map Kinase Inactivation of SMRT Corepressor h_cardiacegfPathway - Role of EGF Receptor Transactivation by GPCRs in Cardiac Hypertrophy h_mCalpainPathway - mCalpain and friends in Cell motility h_ErbB3Pathway - Neuroregulin receptor degredation protein-1 Controls ErbB3 receptor recycling h_egfPathway - EGF Signaling Pathway h_spryPathway - Sprouty regulation of tyrosine kinase signals
Reactome (by CSHL, EBI, and GO)
Protein P01133 (Reactome details) participates in the following event(s):
R-HSA-177942 EGFR binds EGF ligand R-HSA-1220612 Binding of EGF to ligand-responsive EGFR mutants R-HSA-177946 Pro-EGF is cleaved to form mature EGF R-HSA-481007 Exocytosis of platelet alpha granule contents R-HSA-177922 EGFR dimerization R-HSA-1977959 ERBB4 forms heterodimers with EGFR R-HSA-182993 Ubiquitination of stimulated EGFR (CBL) R-HSA-182986 CBL-mediated ubiquitination of CIN85 R-HSA-183036 Ubiquitination of stimulated EGFR (CBL:GRB2) R-HSA-183002 Beta-Pix:CDC42:GTP binds CBL in EGF:p-6Y-EGFR:CBL:CIN85 R-HSA-8867044 EGFR binds EPS15, EPN1, EPS15L1 R-HSA-182994 Assembly of EGFR complex in clathrin-coated vesicles R-HSA-183058 Phosphorylation of CBL (EGFR:GRB2:CBL) R-HSA-183072 EGFR non-clathrin mediated endocytosis R-HSA-183089 CBL binds and ubiquitinates phosphorylated Sprouty R-HSA-182969 Phosphorylation of CBL (EGFR:CBL) R-HSA-177934 EGFR autophosphorylation R-HSA-177937 Phosphorylation of EGFR by SRC kinase R-HSA-1225978 Covalent tyrosine kinase inhibitors bind and inhibit wild-type EGF:EGFR dimers R-HSA-1963589 ERBB2 forms heterodimers with ligand-activated ERBB receptors: EGFR, ERBB3 and ERBB4 R-HSA-177925 SHC1 binds to the phosphorylated EGF receptor:ligand complex R-HSA-177941 GRB2:GAB1 binds to phosphorylated EGFR R-HSA-177943 GRB2:SOS1 complex binds to EGF:EGFR complex R-HSA-183055 Binding of CBL to EGFR R-HSA-183067 Localization of CBL:GRB2 to the membrane R-HSA-212706 Phospholipase C-gamma1 binds to the activated EGF receptor R-HSA-8864029 PTPN12 dephosphorylates EGFR at Y1148 (Y1172) R-HSA-9018573 NOTCH3 binds activated EGFR R-HSA-212713 Active PLC-gamma1 dissociates from EGFR R-HSA-9018572 EGFR phosphorylates NOTCH3 R-HSA-8867041 EGFR phosphorylates EPS15 R-HSA-8867047 PTPN3 dephosphorylates EPS15 R-HSA-8951490 CIN85 dissociates from EGF:p-6Y-EGFR:CBL:Beta-Pix:CDC42:GTP:CIN85 R-HSA-183084 CBL escapes CDC42-mediated inhibition by down-regulating the adaptor molecule Beta-Pix R-HSA-182990 Sprouty sequesters CBL away from active EGFR R-HSA-1220613 EGF-induced dimerization of ligand-responsive EGFR mutants R-NUL-1251923 Plcg1 binds P-ERBB2:P-EGFR R-HSA-8866279 Epsin family proteins bind ubiquitinated cargo R-HSA-1963582 Trans-autophosphorylation of ERBB2 heterodimers R-HSA-1963586 SRC family kinases phosphorylate ERBB2 R-HSA-1963581 Trans-autophosphorylation of p-Y877-ERBB2 heterodimers R-HSA-177927 PI3K binds to EGF:EGFR:GRB2:GAB1 R-HSA-177944 Activation of SHP2 through the binding to phospho-Gab1 R-HSA-177930 GAB1 phosphorylation by EGFR kinase R-HSA-177933 SHC1 phosphorylation by phosphorylated EGFR R-HSA-177936 GRB2:SOS1 binds to phosphorylated SHC1 in complex with EGFR R-HSA-177924 Dephosphorylation of Gab1 by SHP2 R-HSA-212710 EGFR activates PLC-gamma1 by phosphorylation R-HSA-177935 SHP2 dephosphorylates Tyr 992 on EGFR R-HSA-1220611 Covalent tyrosine kinase inhibitors bind and inactivate EGFR kinase domain mutant dimers resistant to non-covalent tyrosine kinase inhibitors R-HSA-1220610 Non-covalent tyrosine kinase inhibitors bind and inactivate sensitive ligand-responsive EGFR cancer mutants R-NUL-1251929 Plcg1 phosphorylation by P-ERBB2:P-EGFR R-NUL-1248744 Shc1 binds phosphorylated ERBB2:EGFR heterodimers R-HSA-1250488 GRB2:SOS1 complex binds phosphorylated EGFR:ERBB2 heterodimer R-HSA-1251944 PLCG1 binds to p-ERBB2:p-EGFR R-HSA-1306963 Binding of GRB2:GAB1 to p-ERBB2:p-EGFR R-HSA-8864105 PTPN18 binds ERBB2:EGFR heterodimers R-HSA-1251922 PLCG1 phosphorylation by p-EGFR:p-ERBB2 R-HSA-177938 SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1) R-HSA-183051 CBL ubiquitinates Sprouty R-HSA-8857925 Inhibition of PP2A activity by phosphorylation of the catalytic subunit at tyrosine Y307 R-HSA-1169421 Trans-autophosphorylation of activated ligand-responsive EGFR mutant dimers R-HSA-1963563 MATK (CSK homologous kinase) binds phosphorylated ERBB2 R-HSA-1963578 SHC1 binds phosphorylated ERBB2 heterodimers R-HSA-6785636 Phosphorylated ERBB2 heterodimers bind MEMO1 R-HSA-8847995 Activated ERBB2 binds PTK6 (BRK) R-HSA-8863804 PTPN12 dephosphorylates ERBB2 on tyrosine Y1248 R-HSA-8848005 ERBB2 promotes PTK6 autophosphorylation R-HSA-1306965 Binding of PI3K to GRB2:GAB1 in complex with phosphorylated heterodimer of ERBB2 and EGFR. R-HSA-8864125 PTPN18 dephosphorylates ERBB2 at Y1196, Y1112 and Y1248 R-HSA-1225947 Binding of SHC1 to p-6Y-EGFR mutants R-HSA-1225949 Binding of CBL to ligand-responsive p-6Y-EGFR mutants R-HSA-1225950 Binding of GRB2:SOS1 complex to phosphorylated ligand-responsive EGFR mutants R-HSA-1226016 Binding of GRB2:GAB1:PIK3R1 complex to ligand-responsive p-6Y-EGFR mutants R-HSA-1247841 PLCG1 binds to ligand-responsive p-6Y-EGFR mutants R-HSA-1247842 Dissociation of phosphorylated PLCG1 from ligand-responsive p-6Y-EGFR mutants R-HSA-8867756 CLASP proteins and cargo are recruited to the nascent clathrin-coated pit R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange R-HSA-177939 PI3K converts phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3) R-HSA-177923 Sustained activation of SRC kinase by SHP2 R-HSA-177926 Dephosphorylation of PAG by SHP2 R-HSA-177945 SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:SHC1:GRB2:SOS1) R-HSA-1250195 SHC1 phosphorylation by ERBB2 heterodimers R-HSA-1250486 Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 heterodimers R-HSA-6785648 MEMO1 binds RHOA:GTP:DIAPH1 R-HSA-1250498 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and phosphorylated EGFR:ERBB2 heterodimers. R-HSA-1225961 Phosphorylated SHC1 in complex with ligand-responsive p-6Y-EGFR mutants recruits GRB2:SOS1 complex R-HSA-1225952 Phosphorylation of SHC1 by ligand-responsive p-6Y-EGFR mutants R-HSA-1225960 Phosphorylation of CBL by ligand-responsive p-6Y-EGFR mutants R-HSA-1226012 Binding of PI3K p110 subunit alpha (PIK3CA) to complex of GRB2:GAB1:PIK3R1 and ligand-responsive p-6Y-EGFR mutants R-HSA-1247844 Phosphorylation of PLCG1 by ligand-responsive p-6Y-EGFR mutants R-HSA-8868071 Clathrin recruits PIK3C2A R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission R-HSA-8868648 SYNJ hydrolyze PI(4,5)P2 to PI(4)P R-HSA-8871194 RAB5 and GAPVD1 bind AP-2 R-HSA-8868658 HSPA8-mediated ATP hydrolysis promotes vesicle uncoating R-HSA-8868659 Clathrin recruits auxilins to the clathrin-coated vesicle R-HSA-8868660 Auxilin recruits HSPA8:ATP to the clathrin-coated vesicle R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3 R-HSA-1225951 SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with ligand-responsive p-6Y-EGFR mutants) R-HSA-8867754 F- and N- BAR domain proteins bind the clathrin-coated pit R-HSA-8868230 SNX9 recruits components of the actin polymerizing machinery R-HSA-1250463 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-SHC1:Phosphorylated ERBB2 heterodimers R-HSA-1306957 PIP2 to PIP3 conversion by PI3K bound to GRB2:GAB1 in complex with phosphorylated heterodimer of ERBB2 and EGFR R-HSA-1225957 SOS-mediated nucleotide exchange of RAS (mediated by GRB2:SOS1 in complex with phosphorylated SHC1 and ligand-responsive p-6Y-EGFR mutants) R-HSA-1226014 Conversion of PIP2 to PIP3 by PI3K bound to ligand-responsive p-6Y-EGFR mutants R-HSA-8868072 Clathrin-associated PIK3C2A phosphorylates PI(4)P to PI(3,4)P2 R-HSA-8868236 BAR domain proteins recruit dynamin R-HSA-8868651 Endophilins recruit synaptojanins to the clathrin-coated pit R-HSA-177929 Signaling by EGFR R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants R-HSA-5637810 Constitutive Signaling by EGFRvIII R-HSA-114608 Platelet degranulation R-HSA-1236394 Signaling by ERBB4 R-HSA-182971 EGFR downregulation R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-5637815 Signaling by Ligand-Responsive EGFR Variants in Cancer R-HSA-5637812 Signaling by EGFRvIII in Cancer R-HSA-76005 Response to elevated platelet cytosolic Ca2+ R-HSA-5638303 Inhibition of Signaling by Overexpressed EGFR R-HSA-1227986 Signaling by ERBB2 R-HSA-180336 SHC1 events in EGFR signaling R-HSA-180292 GAB1 signalosome R-HSA-179812 GRB2 events in EGFR signaling R-HSA-212718 EGFR interacts with phospholipase C-gamma R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis R-HSA-162582 Signal Transduction R-HSA-1643713 Signaling by EGFR in Cancer R-HSA-76002 Platelet activation, signaling and aggregation R-HSA-5638302 Signaling by Overexpressed Wild-Type EGFR in Cancer R-HSA-9012852 Signaling by NOTCH3 R-HSA-1963640 GRB2 events in ERBB2 signaling R-HSA-1251932 PLCG1 events in ERBB2 signaling R-HSA-1963642 PI3K events in ERBB2 signaling R-HSA-8863795 Downregulation of ERBB2 signaling R-HSA-8856828 Clathrin-mediated endocytosis R-HSA-5663202 Diseases of signal transduction R-HSA-109582 Hemostasis R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-157118 Signaling by NOTCH R-HSA-1250196 SHC1 events in ERBB2 signaling R-HSA-6785631 ERBB2 Regulates Cell Motility R-HSA-8847993 ERBB2 Activates PTK6 Signaling R-HSA-199991 Membrane Trafficking R-HSA-1643685 Disease R-HSA-5673001 RAF/MAP kinase cascade R-HSA-199418 Negative regulation of the PI3K/AKT network R-HSA-8848021 Signaling by PTK6 R-HSA-5653656 Vesicle-mediated transport R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-1257604 PIP3 activates AKT signaling R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases R-HSA-5683057 MAPK family signaling cascades R-HSA-2219528 PI3K/AKT Signaling in Cancer R-HSA-9006925 Intracellular signaling by second messengers
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
