EGF

Protein identityUniProt · HPA

UniProt accession

P01133

Gene

EGF

Ensembl

ENSG00000138798

Chromosome

4

Canonical length

1207 aa

Protein class

Cancer-related genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted membrane proteins, RAS pathway related proteins

OverviewNCBI Gene

This gene encodes a member of the epidermal growth factor superfamily. The encoded preproprotein is proteolytically processed to generate the 53-amino acid epidermal growth factor peptide. This protein acts a potent mitogenic factor that plays an important role in the growth, proliferation and differentiation of numerous cell types. This protein acts by binding with high affinity to the cell surface receptor, epidermal growth factor receptor. Defects in this gene are the cause of hypomagnesemia type 4. Dysregulation of this gene has been associated with the growth and progression of certain cancers. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

Canonical amino-acid sequenceUniProt

1207 residues, UniProt reviewed canonical sequence.

>P01133|EGF
     1  MLLTLIILLP VVSKFSFVSL SAPQHWSCPE GTLAGNGNST CVGPAPFLIF SHGNSIFRID
    61  TEGTNYEQLV VDAGVSVIMD FHYNEKRIYW VDLERQLLQR VFLNGSRQER VCNIEKNVSG
   121  MAINWINEEV IWSNQQEGII TVTDMKGNNS HILLSALKYP ANVAVDPVER FIFWSSEVAG
   181  SLYRADLDGV GVKALLETSE KITAVSLDVL DKRLFWIQYN REGSNSLICS CDYDGGSVHI
   241  SKHPTQHNLF AMSLFGDRIF YSTWKMKTIW IANKHTGKDM VRINLHSSFV PLGELKVVHP
   301  LAQPKAEDDT WEPEQKLCKL RKGNCSSTVC GQDLQSHLCM CAEGYALSRD RKYCEDVNEC
   361  AFWNHGCTLG CKNTPGSYYC TCPVGFVLLP DGKRCHQLVS CPRNVSECSH DCVLTSEGPL
   421  CFCPEGSVLE RDGKTCSGCS SPDNGGCSQL CVPLSPVSWE CDCFPGYDLQ LDEKSCAASG
   481  PQPFLLFANS QDIRHMHFDG TDYGTLLSQQ MGMVYALDHD PVENKIYFAH TALKWIERAN
   541  MDGSQRERLI EEGVDVPEGL AVDWIGRRFY WTDRGKSLIG RSDLNGKRSK IITKENISQP
   601  RGIAVHPMAK RLFWTDTGIN PRIESSSLQG LGRLVIASSD LIWPSGITID FLTDKLYWCD
   661  AKQSVIEMAN LDGSKRRRLT QNDVGHPFAV AVFEDYVWFS DWAMPSVMRV NKRTGKDRVR
   721  LQGSMLKPSS LVVVHPLAKP GADPCLYQNG GCEHICKKRL GTAWCSCREG FMKASDGKTC
   781  LALDGHQLLA GGEVDLKNQV TPLDILSKTR VSEDNITESQ HMLVAEIMVS DQDDCAPVGC
   841  SMYARCISEG EDATCQCLKG FAGDGKLCSD IDECEMGVPV CPPASSKCIN TEGGYVCRCS
   901  EGYQGDGIHC LDIDECQLGE HSCGENASCT NTEGGYTCMC AGRLSEPGLI CPDSTPPPHL
   961  REDDHHYSVR NSDSECPLSH DGYCLHDGVC MYIEALDKYA CNCVVGYIGE RCQYRDLKWW
  1021  ELRHAGHGQQ QKVIVVAVCV VVLVMLLLLS LWGAHYYRTQ KLLSKNPKNP YEESSRDVRS
  1081  RRPADTEDGM SSCPQPWFVV IKEHQDLKNG GQPVAGEDGQ AADGSMQPTS WRQEPQLCGM
  1141  GTEQGCWIPV SSDKGSCPQV MERSFHMPSY GTQTLEGGVE KPHSLLSANP LWQQRALDPP
  1201  HQMELTQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against EGF can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.39

Highest tissue expression

103 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about EGF.

Disease | AllUniProt

Conditions EGF is implicated in, by any mechanism.

• Hypomagnesemia 4 (HOMG4) MIM:611718

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 663 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Renal hypomagnesemia 4

ReferencesPubMed · IEDB

Publications for EGF from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.74

gnomAD pLI

0

gnomAD missense Z

0.94

DepMap mean gene effect

-0.07

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• branching morphogenesis of an epithelial tube
• cerebellar granule cell precursor proliferation
• epidermal growth factor receptor signaling pathway
• epithelial cell proliferation
• ERBB2-EGFR signaling pathway
• ERK1 and ERK2 cascade
• mammary gland alveolus development
• negative regulation of cholesterol efflux
• negative regulation of epidermal growth factor receptor signaling pathway
• negative regulation of secretion
• positive regulation of canonical Wnt signaling pathway
• positive regulation of cell migration
• positive regulation of cell population proliferation
• positive regulation of cerebellar granule cell precursor proliferation
• positive regulation of DNA binding
• positive regulation of DNA-templated transcription
• positive regulation of endothelial cell migration
• positive regulation of endothelial cell proliferation
• positive regulation of epithelial tube formation
• positive regulation of gene expression
• positive regulation of hyaluronan biosynthetic process
• positive regulation of MAPK cascade
• positive regulation of mitotic nuclear division
• positive regulation of peptidyl-threonine phosphorylation
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of phosphorylation
• positive regulation of protein localization to early endosome
• positive regulation of receptor internalization
• positive regulation of ubiquitin-dependent protein catabolic process
• protein ubiquitination
• regulation of calcium ion import
• regulation of protein localization to cell surface
• regulation of receptor signaling pathway via JAK-STAT
• ubiquitin-dependent endocytosis
• ubiquitin-dependent protein catabolic process

Molecular functions

• calcium ion binding
• epidermal growth factor receptor binding
• growth factor activity
• guanyl-nucleotide exchange factor activity
• receptor ligand activity
• transmembrane receptor protein tyrosine kinase activator activity

Cellular components

• clathrin-coated endocytic vesicle membrane
• extracellular exosome
• extracellular region
• extracellular space
• lysosomal membrane
• plasma membrane
• platelet alpha granule lumen

Protein domainsUniProt · Pfam · InterPro

• LDLR class B repeat
• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• EGF-like calcium-binding domain
• Growth factor receptor cysteine-rich domain superfamily
• Six-bladed beta-propeller, TolB-like
• EGF-like calcium-binding, conserved site
• NOTCH1, EGF-like calcium-binding domain
• EGF-like domain
• Low-density lipoprotein receptor repeat class B
• Calcium-binding EGF domain
• Coagulation Factor Xa inhibitory site
• Pro-epidermal growth factor

KeywordsUniProt

• Disulfide bond
• EGF-like domain
• Glycoprotein
• Growth factor
• Membrane
• Primary hypomagnesemia
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of EGF in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• EGFR
• RHBDF1
• RHBDF2