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Protein

Pro-epidermal growth factor

Gene

EGF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Can induce neurite outgrowth in motoneurons of the pond snail Lymnaea stagnalis in vitro (PubMed:10964941).2 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGrowth factor

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-1227986 Signaling by ERBB2
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
R-HSA-1236394 Signaling by ERBB4
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1251932 PLCG1 events in ERBB2 signaling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-177929 Signaling by EGFR
R-HSA-179812 GRB2 events in EGFR signaling
R-HSA-180292 GAB1 signalosome
R-HSA-180336 SHC1 events in EGFR signaling
R-HSA-182971 EGFR downregulation
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-1963642 PI3K events in ERBB2 signaling
R-HSA-212718 EGFR interacts with phospholipase C-gamma
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5637810 Constitutive Signaling by EGFRvIII
R-HSA-5638303 Inhibition of Signaling by Overexpressed EGFR
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6785631 ERBB2 Regulates Cell Motility
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8847993 ERBB2 Activates PTK6 Signaling
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-8863795 Downregulation of ERBB2 signaling
R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus
SignaLinkiP01133
SIGNORiP01133

Names & Taxonomyi

Protein namesi
Recommended name:
Pro-epidermal growth factor
Short name:
EGF
Cleaved into the following chain:
Alternative name(s):
Urogastrone
Gene namesi
Name:EGF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000138798.11
HGNCiHGNC:3229 EGF
MIMi131530 gene
neXtProtiNX_P01133

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 1032ExtracellularSequence analysisAdd BLAST1010
Transmembranei1033 – 1053HelicalSequence analysisAdd BLAST21
Topological domaini1054 – 1207CytoplasmicSequence analysisAdd BLAST154

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Hypomagnesemia 4 (HOMG4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by massive renal hypomagnesemia and normal levels of serum calcium and calcium excretion. Clinical features include seizures, mild-to moderate psychomotor retardation, and brisk tendon reflexes.
See also OMIM:611718
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0394741070P → L in HOMG4; affects basolateral sorting of pro-EGF preventing the hormone to stimulate EGFR; lack of TRPM6 activation. 1 PublicationCorresponds to variant dbSNP:rs121434567EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Primary hypomagnesemia

Organism-specific databases

DisGeNETi1950
MalaCardsiEGF
MIMi611718 phenotype
OpenTargetsiENSG00000138798
Orphaneti210159 Adult hepatocellular carcinoma
34527 Familial primary hypomagnesemia with normocalciuria and normocalcemia
PharmGKBiPA27664

Chemistry databases

ChEMBLiCHEMBL5734
DrugBankiDB04454 Alpha-Aminobutyric Acid
DB00364 Sucralfate
DB05007 XL647

Polymorphism and mutation databases

BioMutaiEGF
DMDMi251757262

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000000754023 – 1207Pro-epidermal growth factorAdd BLAST1185
ChainiPRO_0000007541971 – 1023Epidermal growth factorAdd BLAST53

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi38N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi104N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi117N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi148N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi318 ↔ 330PROSITE-ProRule annotation
Glycosylationi324N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi325 ↔ 339PROSITE-ProRule annotation
Disulfide bondi341 ↔ 354PROSITE-ProRule annotation
Disulfide bondi360 ↔ 371PROSITE-ProRule annotation
Disulfide bondi367 ↔ 380PROSITE-ProRule annotation
Disulfide bondi382 ↔ 395PROSITE-ProRule annotation
Disulfide bondi401 ↔ 412PROSITE-ProRule annotation
Glycosylationi404N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi408 ↔ 421PROSITE-ProRule annotation
Disulfide bondi423 ↔ 436PROSITE-ProRule annotation
Disulfide bondi439 ↔ 451PROSITE-ProRule annotation
Disulfide bondi447 ↔ 461PROSITE-ProRule annotation
Disulfide bondi463 ↔ 476PROSITE-ProRule annotation
Glycosylationi596N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi745 ↔ 756PROSITE-ProRule annotation
Disulfide bondi752 ↔ 765PROSITE-ProRule annotation
Disulfide bondi767 ↔ 780PROSITE-ProRule annotation
Glycosylationi815N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi835 ↔ 846PROSITE-ProRule annotation
Disulfide bondi840 ↔ 855PROSITE-ProRule annotation
Disulfide bondi857 ↔ 868PROSITE-ProRule annotation
Disulfide bondi874 ↔ 888PROSITE-ProRule annotation
Disulfide bondi881 ↔ 897PROSITE-ProRule annotation
Disulfide bondi899 ↔ 910PROSITE-ProRule annotation
Disulfide bondi916 ↔ 929PROSITE-ProRule annotation
Disulfide bondi923 ↔ 938PROSITE-ProRule annotation
Glycosylationi926N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi940 ↔ 951PROSITE-ProRule annotation
Disulfide bondi976 ↔ 990
Disulfide bondi984 ↔ 1001
Disulfide bondi1003 ↔ 1012

Post-translational modificationi

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).1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP01133
PeptideAtlasiP01133
PRIDEiP01133

PTM databases

GlyConnecti709
iPTMnetiP01133
PhosphoSitePlusiP01133
UniCarbKBiP01133

Miscellaneous databases

PMAP-CutDBiP01133

Expressioni

Tissue specificityi

Expressed in kidney, salivary gland, cerebrum and prostate.1 Publication

Gene expression databases

BgeeiENSG00000138798
CleanExiHS_EGF
GenevisibleiP01133 HS

Interactioni

Subunit structurei

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).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: UniProtKB
  • growth factor activity Source: HGNC
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome
  • Wnt-protein binding Source: GO_Central

Protein-protein interaction databases

BioGridi108270, 16 interactors
DIPiDIP-5767N
IntActiP01133, 8 interactors
MINTiP01133
STRINGi9606.ENSP00000265171

Structurei

Secondary structure

11207
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi979 – 981Combined sources3
Beta strandi982 – 984Combined sources3
Turni985 – 987Combined sources3
Beta strandi989 – 993Combined sources5
Turni994 – 997Combined sources4
Beta strandi998 – 1003Combined sources6
Beta strandi1007 – 1009Combined sources3
Turni1018 – 1021Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IVOX-ray3.30C/D971-1023[»]
1JL9X-ray3.00A/B971-1021[»]
1NQLX-ray2.80B971-1023[»]
1P9JNMR-A976-1022[»]
2KV4NMR-A971-1023[»]
3NJPX-ray3.30C/D975-1021[»]
ProteinModelPortaliP01133
SMRiP01133
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01133

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati86 – 127LDL-receptor class B 1Add BLAST42
Repeati128 – 169LDL-receptor class B 2Add BLAST42
Repeati170 – 211LDL-receptor class B 3Add BLAST42
Repeati212 – 258LDL-receptor class B 4Add BLAST47
Domaini314 – 355EGF-like 1PROSITE-ProRule annotationAdd BLAST42
Domaini356 – 396EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd BLAST41
Domaini397 – 437EGF-like 3PROSITE-ProRule annotationAdd BLAST41
Domaini435 – 477EGF-like 4PROSITE-ProRule annotationAdd BLAST43
Repeati483 – 523LDL-receptor class B 5Add BLAST41
Repeati524 – 566LDL-receptor class B 6Add BLAST43
Repeati567 – 609LDL-receptor class B 7Add BLAST43
Repeati610 – 653LDL-receptor class B 8Add BLAST44
Repeati654 – 696LDL-receptor class B 9Add BLAST43
Domaini741 – 781EGF-like 5PROSITE-ProRule annotationAdd BLAST41
Domaini831 – 869EGF-like 6PROSITE-ProRule annotationAdd BLAST39
Domaini870 – 911EGF-like 7; calcium-bindingPROSITE-ProRule annotationAdd BLAST42
Domaini912 – 952EGF-like 8; calcium-bindingPROSITE-ProRule annotationAdd BLAST41
Domaini972 – 1013EGF-like 9PROSITE-ProRule annotationAdd BLAST42

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni801 – 807O-glycosylated at one site7

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IPSY Eukaryota
ENOG410ZVIM LUCA
GeneTreeiENSGT00910000144086
HOGENOMiHOG000112345
HOVERGENiHBG003858
InParanoidiP01133
KOiK04357
OMAiKIYFAHT
OrthoDBiEOG091G014V
PhylomeDBiP01133
TreeFamiTF315253

Family and domain databases

Gene3Di2.120.10.30, 2 hits
InterProiView protein in InterPro
IPR011042 6-blade_b-propeller_TolB-like
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000152 EGF-type_Asp/Asn_hydroxyl_site
IPR018097 EGF_Ca-bd_CS
IPR009030 Growth_fac_rcpt_cys_sf
IPR000033 LDLR_classB_rpt
IPR016317 Pro-epidermal_GF
PfamiView protein in Pfam
PF00008 EGF, 1 hit
PF07645 EGF_CA, 3 hits
PF00058 Ldl_recept_b, 4 hits
PIRSFiPIRSF001778 Pro-epidermal_growth_factor, 1 hit
SMARTiView protein in SMART
SM00181 EGF, 9 hits
SM00179 EGF_CA, 5 hits
SM00135 LY, 9 hits
SUPFAMiSSF57184 SSF57184, 4 hits
PROSITEiView protein in PROSITE
PS00010 ASX_HYDROXYL, 3 hits
PS00022 EGF_1, 1 hit
PS01186 EGF_2, 7 hits
PS50026 EGF_3, 5 hits
PS01187 EGF_CA, 3 hits
PS51120 LDLRB, 9 hits

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P01133-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLLTLIILLP VVSKFSFVSL SAPQHWSCPE GTLAGNGNST CVGPAPFLIF
60 70 80 90 100
SHGNSIFRID TEGTNYEQLV VDAGVSVIMD FHYNEKRIYW VDLERQLLQR
110 120 130 140 150
VFLNGSRQER VCNIEKNVSG MAINWINEEV IWSNQQEGII TVTDMKGNNS
160 170 180 190 200
HILLSALKYP ANVAVDPVER FIFWSSEVAG SLYRADLDGV GVKALLETSE
210 220 230 240 250
KITAVSLDVL DKRLFWIQYN REGSNSLICS CDYDGGSVHI SKHPTQHNLF
260 270 280 290 300
AMSLFGDRIF YSTWKMKTIW IANKHTGKDM VRINLHSSFV PLGELKVVHP
310 320 330 340 350
LAQPKAEDDT WEPEQKLCKL RKGNCSSTVC GQDLQSHLCM CAEGYALSRD
360 370 380 390 400
RKYCEDVNEC AFWNHGCTLG CKNTPGSYYC TCPVGFVLLP DGKRCHQLVS
410 420 430 440 450
CPRNVSECSH DCVLTSEGPL CFCPEGSVLE RDGKTCSGCS SPDNGGCSQL
460 470 480 490 500
CVPLSPVSWE CDCFPGYDLQ LDEKSCAASG PQPFLLFANS QDIRHMHFDG
510 520 530 540 550
TDYGTLLSQQ MGMVYALDHD PVENKIYFAH TALKWIERAN MDGSQRERLI
560 570 580 590 600
EEGVDVPEGL AVDWIGRRFY WTDRGKSLIG RSDLNGKRSK IITKENISQP
610 620 630 640 650
RGIAVHPMAK RLFWTDTGIN PRIESSSLQG LGRLVIASSD LIWPSGITID
660 670 680 690 700
FLTDKLYWCD AKQSVIEMAN LDGSKRRRLT QNDVGHPFAV AVFEDYVWFS
710 720 730 740 750
DWAMPSVMRV NKRTGKDRVR LQGSMLKPSS LVVVHPLAKP GADPCLYQNG
760 770 780 790 800
GCEHICKKRL GTAWCSCREG FMKASDGKTC LALDGHQLLA GGEVDLKNQV
810 820 830 840 850
TPLDILSKTR VSEDNITESQ HMLVAEIMVS DQDDCAPVGC SMYARCISEG
860 870 880 890 900
EDATCQCLKG FAGDGKLCSD IDECEMGVPV CPPASSKCIN TEGGYVCRCS
910 920 930 940 950
EGYQGDGIHC LDIDECQLGE HSCGENASCT NTEGGYTCMC AGRLSEPGLI
960 970 980 990 1000
CPDSTPPPHL REDDHHYSVR NSDSECPLSH DGYCLHDGVC MYIEALDKYA
1010 1020 1030 1040 1050
CNCVVGYIGE RCQYRDLKWW ELRHAGHGQQ QKVIVVAVCV VVLVMLLLLS
1060 1070 1080 1090 1100
LWGAHYYRTQ KLLSKNPKNP YEESSRDVRS RRPADTEDGM SSCPQPWFVV
1110 1120 1130 1140 1150
IKEHQDLKNG GQPVAGEDGQ AADGSMQPTS WRQEPQLCGM GTEQGCWIPV
1160 1170 1180 1190 1200
SSDKGSCPQV MERSFHMPSY GTQTLEGGVE KPHSLLSANP LWQQRALDPP

HQMELTQ
Length:1,207
Mass (Da):133,994
Last modified:July 7, 2009 - v2
Checksum:i3C787F1D405CFAF1
GO
Isoform 2 (identifier: P01133-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     314-355: Missing.

Show »
Length:1,165
Mass (Da):129,256
Checksum:i5449AE11FA9276B5
GO
Isoform 3 (identifier: P01133-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     912-952: Missing.

Note: No experimental confirmation available. Gene prediction based on cDNA data.
Show »
Length:1,166
Mass (Da):129,746
Checksum:i4872256969C28678
GO

Sequence cautioni

The sequence AAR84237 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti302A → T in BAG61319 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02016116S → R1 PublicationCorresponds to variant dbSNP:rs11568849EnsemblClinVar.1
Natural variantiVAR_033825151H → Y. Corresponds to variant dbSNP:rs9991664EnsemblClinVar.1
Natural variantiVAR_020968257D → H1 PublicationCorresponds to variant dbSNP:rs11568911EnsemblClinVar.1
Natural variantiVAR_033826292L → H. Corresponds to variant dbSNP:rs35191533Ensembl.1
Natural variantiVAR_020162431R → K1 PublicationCorresponds to variant dbSNP:rs11568943EnsemblClinVar.1
Natural variantiVAR_020969638S → R1 PublicationCorresponds to variant dbSNP:rs11568992Ensembl.1
Natural variantiVAR_002275708M → I1 PublicationCorresponds to variant dbSNP:rs2237051EnsemblClinVar.1
Natural variantiVAR_020163723G → R. Corresponds to variant dbSNP:rs6413481Ensembl.1
Natural variantiVAR_020164784D → V1 PublicationCorresponds to variant dbSNP:rs11569017EnsemblClinVar.1
Natural variantiVAR_020165842M → T1 PublicationCorresponds to variant dbSNP:rs11569046EnsemblClinVar.1
Natural variantiVAR_020970920E → V2 PublicationsCorresponds to variant dbSNP:rs4698803EnsemblClinVar.1
Natural variantiVAR_020971981D → E1 PublicationCorresponds to variant dbSNP:rs11569086Ensembl.1
Natural variantiVAR_0201661043L → F1 PublicationCorresponds to variant dbSNP:rs11569098EnsemblClinVar.1
Natural variantiVAR_0394741070P → L in HOMG4; affects basolateral sorting of pro-EGF preventing the hormone to stimulate EGFR; lack of TRPM6 activation. 1 PublicationCorresponds to variant dbSNP:rs121434567EnsemblClinVar.1
Natural variantiVAR_0209721084A → G1 PublicationCorresponds to variant dbSNP:rs11569111Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041586314 – 355Missing in isoform 2. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_047190912 – 952Missing in isoform 3. CuratedAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04571 mRNA Translation: CAA28240.1
AY506357 Genomic DNA Translation: AAR84237.1 Sequence problems.
AK299306 mRNA Translation: BAG61319.1
AC004050 Genomic DNA No translation available.
AC005509 Genomic DNA No translation available.
BC093731 mRNA Translation: AAH93731.1
BC113461 mRNA Translation: AAI13462.1
CCDSiCCDS3689.1 [P01133-1]
CCDS54794.1 [P01133-3]
CCDS54795.1 [P01133-2]
PIRiA25531 EGHU
RefSeqiNP_001171601.1, NM_001178130.2 [P01133-3]
NP_001171602.1, NM_001178131.2 [P01133-2]
NP_001954.2, NM_001963.5 [P01133-1]
UniGeneiHs.419815

Genome annotation databases

EnsembliENST00000265171; ENSP00000265171; ENSG00000138798 [P01133-1]
ENST00000503392; ENSP00000421384; ENSG00000138798 [P01133-3]
ENST00000509793; ENSP00000424316; ENSG00000138798 [P01133-2]
GeneIDi1950
KEGGihsa:1950
UCSCiuc003hzy.5 human [P01133-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiEGF_HUMAN
AccessioniPrimary (citable) accession number: P01133
Secondary accession number(s): B4DRK7
, E7EVD2, E9PBF0, Q52LZ6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 7, 2009
Last modified: May 23, 2018
This is version 205 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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