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Reviewed, UniProtKB/Swiss-Prot P01133 (EGF_HUMAN)

Last modified February 9, 2010. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Pro-epidermal growth factor
      Short name=EGF
Cleaved into the following chain:
    1- Recommended name:
            Epidermal growth factor
        Alternative name(s):
            Urogastrone
Gene names
Name: EGF
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length1207 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

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. Ref.7

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Expressed in kidney, salivary gland, cerebrum and prostate. Ref.7

Involvement in 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. Ref.7

Sequence similarities

Contains 9 EGF-like domains.

Contains 9 LDL-receptor class B repeats.

Sequence caution

The sequence AAR84237.1 differs from that shown. Reason: Erroneous gene model prediction.

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Ontologies

Keywords
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Primary hypomagnesemia
   DomainEGF-like domain
Repeat
Signal
Transmembrane
   Molecular functionGrowth factor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processDNA replication

Traceable author statement. Source: ProtInc

angiogenesis

Inferred from direct assay. Source: HGNC

negative regulation of secretion

Inferred from direct assay. Source: UniProtKB

positive regulation of MAP kinase activity

Inferred from direct assay. Source: HGNC

positive regulation of epidermal growth factor receptor activity

Traceable author statement. Source: UniProtKB

positive regulation of mitosis

Inferred from direct assay. Source: HGNC

positive regulation of phosphorylation

Inferred from direct assay. Source: HGNC

   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane Ref.1

Traceable author statement. Source: ProtInc

platelet alpha granule lumen

Inferred from Experiment. Source: Reactome

   Molecular functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

epidermal growth factor receptor binding

Traceable author statement. Source: UniProtKB

growth factor activity

Inferred from direct assay. Source: MGI

transmembrane receptor protein tyrosine kinase activator activity

Traceable author statement. Source: UniProtKB

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

EGFRP005332EBI-640857,EBI-297353

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 12071185Pro-epidermal growth factor
PRO_0000007540
Chain971 – 102353Epidermal growth factor
PRO_0000007541

Regions

Topological domain23 – 10321010Extracellular Potential
Transmembrane1033 – 105321 Potential
Topological domain1054 – 1207154Cytoplasmic Potential
Repeat86 – 12742LDL-receptor class B 1
Repeat128 – 16942LDL-receptor class B 2
Repeat170 – 21142LDL-receptor class B 3
Repeat212 – 25847LDL-receptor class B 4
Domain314 – 35542EGF-like 1
Domain356 – 39641EGF-like 2; calcium-binding Potential
Domain397 – 43741EGF-like 3
Domain435 – 47743EGF-like 4
Repeat483 – 52341LDL-receptor class B 5
Repeat524 – 56643LDL-receptor class B 6
Repeat567 – 60943LDL-receptor class B 7
Repeat610 – 65344LDL-receptor class B 8
Repeat654 – 69643LDL-receptor class B 9
Domain741 – 78141EGF-like 5
Domain831 – 86939EGF-like 6
Domain870 – 91142EGF-like 7; calcium-binding Potential
Domain912 – 95241EGF-like 8; calcium-binding Potential
Domain972 – 101342EGF-like 9

Amino acid modifications

Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation1041N-linked (GlcNAc...) Potential
Glycosylation1171N-linked (GlcNAc...) Potential
Glycosylation1481N-linked (GlcNAc...) Potential
Glycosylation3241N-linked (GlcNAc...) Potential
Glycosylation4041N-linked (GlcNAc...) Potential
Glycosylation5961N-linked (GlcNAc...) Potential
Glycosylation8151N-linked (GlcNAc...) Potential
Glycosylation9261N-linked (GlcNAc...) Potential
Disulfide bond318 ↔ 330 By similarity
Disulfide bond325 ↔ 339 By similarity
Disulfide bond341 ↔ 354 By similarity
Disulfide bond360 ↔ 371 By similarity
Disulfide bond367 ↔ 380 By similarity
Disulfide bond382 ↔ 395 By similarity
Disulfide bond401 ↔ 412 By similarity
Disulfide bond408 ↔ 421 By similarity
Disulfide bond423 ↔ 436 By similarity
Disulfide bond439 ↔ 451 By similarity
Disulfide bond447 ↔ 461 By similarity
Disulfide bond463 ↔ 476 By similarity
Disulfide bond745 ↔ 756 By similarity
Disulfide bond752 ↔ 765 By similarity
Disulfide bond767 ↔ 780 By similarity
Disulfide bond835 ↔ 846 By similarity
Disulfide bond840 ↔ 855 By similarity
Disulfide bond857 ↔ 868 By similarity
Disulfide bond874 ↔ 888 By similarity
Disulfide bond881 ↔ 897 By similarity
Disulfide bond899 ↔ 910 By similarity
Disulfide bond916 ↔ 929 By similarity
Disulfide bond923 ↔ 938 By similarity
Disulfide bond940 ↔ 951 By similarity
Disulfide bond976 ↔ 990
Disulfide bond984 ↔ 1001
Disulfide bond1003 ↔ 1012

Natural variations

Natural variant161S → R: dbSNP rs11568849. Ref.2
VAR_020161
Natural variant1511H → Y: dbSNP rs9991664.
VAR_033825
Natural variant2571D → H: dbSNP rs11568911. Ref.2
VAR_020968
Natural variant2921L → H: dbSNP rs35191533.
VAR_033826
Natural variant4311R → K: dbSNP rs11568943. Ref.2
VAR_020162
Natural variant6381S → R: dbSNP rs11568992. Ref.2
VAR_020969
Natural variant7081M → I: dbSNP rs2237051. Ref.2
VAR_002275
Natural variant7231G → R: dbSNP rs6413481.
VAR_020163
Natural variant7841D → V: dbSNP rs11569017. Ref.2
VAR_020164
Natural variant8421M → T: dbSNP rs11569046. Ref.2
VAR_020165
Natural variant9201E → V: dbSNP rs4698803. Ref.2
VAR_020970
Natural variant9811D → E: dbSNP rs11569086. Ref.2
VAR_020971
Natural variant10431L → F: dbSNP rs11569098. Ref.2
VAR_020166
Natural variant10701P → L in HOMG4; affects basolateral sorting of pro-EGF preventing the hormone to stimulate EGFR; lack of TRPM6 activation. Ref.7
VAR_039474
Natural variant10841A → G: dbSNP rs11569111. Ref.2
VAR_020972

Secondary structure

1 ........... 1207
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P01133-1 [UniParc].

Last modified July 7, 2009. Version 2.
Checksum: 3C787F1D405CFAF1

FASTA1,207133,994
        10         20         30         40         50         60 
MLLTLIILLP VVSKFSFVSL SAPQHWSCPE GTLAGNGNST CVGPAPFLIF SHGNSIFRID 

        70         80         90        100        110        120 
TEGTNYEQLV VDAGVSVIMD FHYNEKRIYW VDLERQLLQR VFLNGSRQER VCNIEKNVSG 

       130        140        150        160        170        180 
MAINWINEEV IWSNQQEGII TVTDMKGNNS HILLSALKYP ANVAVDPVER FIFWSSEVAG 

       190        200        210        220        230        240 
SLYRADLDGV GVKALLETSE KITAVSLDVL DKRLFWIQYN REGSNSLICS CDYDGGSVHI 

       250        260        270        280        290        300 
SKHPTQHNLF AMSLFGDRIF YSTWKMKTIW IANKHTGKDM VRINLHSSFV PLGELKVVHP 

       310        320        330        340        350        360 
LAQPKAEDDT WEPEQKLCKL RKGNCSSTVC GQDLQSHLCM CAEGYALSRD RKYCEDVNEC 

       370        380        390        400        410        420 
AFWNHGCTLG CKNTPGSYYC TCPVGFVLLP DGKRCHQLVS CPRNVSECSH DCVLTSEGPL 

       430        440        450        460        470        480 
CFCPEGSVLE RDGKTCSGCS SPDNGGCSQL CVPLSPVSWE CDCFPGYDLQ LDEKSCAASG 

       490        500        510        520        530        540 
PQPFLLFANS QDIRHMHFDG TDYGTLLSQQ MGMVYALDHD PVENKIYFAH TALKWIERAN 

       550        560        570        580        590        600 
MDGSQRERLI EEGVDVPEGL AVDWIGRRFY WTDRGKSLIG RSDLNGKRSK IITKENISQP 

       610        620        630        640        650        660 
RGIAVHPMAK RLFWTDTGIN PRIESSSLQG LGRLVIASSD LIWPSGITID FLTDKLYWCD 

       670        680        690        700        710        720 
AKQSVIEMAN LDGSKRRRLT QNDVGHPFAV AVFEDYVWFS DWAMPSVMRV NKRTGKDRVR 

       730        740        750        760        770        780 
LQGSMLKPSS LVVVHPLAKP GADPCLYQNG GCEHICKKRL GTAWCSCREG FMKASDGKTC 

       790        800        810        820        830        840 
LALDGHQLLA GGEVDLKNQV TPLDILSKTR VSEDNITESQ HMLVAEIMVS DQDDCAPVGC 

       850        860        870        880        890        900 
SMYARCISEG EDATCQCLKG FAGDGKLCSD IDECEMGVPV CPPASSKCIN TEGGYVCRCS 

       910        920        930        940        950        960 
EGYQGDGIHC LDIDECQLGE HSCGENASCT NTEGGYTCMC AGRLSEPGLI CPDSTPPPHL 

       970        980        990       1000       1010       1020 
REDDHHYSVR NSDSECPLSH DGYCLHDGVC MYIEALDKYA CNCVVGYIGE RCQYRDLKWW 

      1030       1040       1050       1060       1070       1080 
ELRHAGHGQQ QKVIVVAVCV VVLVMLLLLS LWGAHYYRTQ KLLSKNPKNP YEESSRDVRS 

      1090       1100       1110       1120       1130       1140 
RRPADTEDGM SSCPQPWFVV IKEHQDLKNG GQPVAGEDGQ AADGSMQPTS WRQEPQLCGM 

      1150       1160       1170       1180       1190       1200 
GTEQGCWIPV SSDKGSCPQV MERSFHMPSY GTQTLEGGVE KPHSLLSANP LWQQRALDPP 


HQMELTQ

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References

« Hide 'large scale' references
[1]"Human epidermal growth factor precursor: cDNA sequence, expression in vitro and gene organization."
Bell G.I., Fong N.M., Stempien M.M., Wormsted M.A., Caput D., Ku L., Urdea M.S., Rall L.B., Sanchez-Pescador R.
Nucleic Acids Res. 14:8427-8446(1986) [PubMed: 3491360] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Kidney.
[2]NIEHS SNPs program
Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-16; HIS-257; LYS-431; ARG-638; ILE-708; VAL-784; THR-842; VAL-920; GLU-981; PHE-1043 AND GLY-1084.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon.
[4]"The primary structure of human urogastrone."
Gregory H., Preston B.M.
Int. J. Pept. Protein Res. 9:107-118(1977) [PubMed: 300079] [Abstract]
Cited for: PROTEIN SEQUENCE OF 971-1023.
[5]"The primary structure of human EGF produced by genetic engineering, studied by high-performance tandem mass spectrometry."
Furuya M., Akashi S., Hirayama K.
Biochem. Biophys. Res. Commun. 163:1100-1106(1989) [PubMed: 2789514] [Abstract]
Cited for: PROTEIN SEQUENCE OF 971-1023.
[6]"Human epidermal growth factor. High resolution solution structure and comparison with human transforming growth factor alpha."
Hommel U., Harvey T.S., Driscoll P.C., Campbell I.D.
J. Mol. Biol. 227:271-282(1992) [PubMed: 1522591] [Abstract]
Cited for: STRUCTURE BY NMR OF EGF.
[7]"Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia."
Groenestege W.M.T., Thebault S., van der Wijst J., van den Berg D., Janssen R., Tejpar S., van den Heuvel L.P., van Cutsem E., Hoenderop J.G., Knoers N.V., Bindels R.J.
J. Clin. Invest. 117:2260-2267(2007) [PubMed: 17671655] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, VARIANT HOMG4 LEU-1070, CHARACTERIZATION OF VARIANT HOMG4 LEU-1070.
+Additional computationally mapped references.

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Web resources

NIEHS-SNPs
Wikipedia

Epidermal growth factor entry

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		X04571 mRNA. Translation: CAA28240.1.
AY506357 Genomic DNA. Translation: AAR84237.1. Sequence problems.
BC093731 mRNA. Translation: AAH93731.1.
BC113461 mRNA. Translation: AAI13462.1.
IPIIPI00000073.
PIREGHU. A25531.
RefSeqNP_001954.2.
UniGeneHs.419815

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IVOX-ray3.30C/D971-1023[»]
1JL9X-ray3.00A/B971-1021[»]
1NQLX-ray2.80B971-1023[»]
1P9JNMR-A974-1022[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-5767N.
IntActP01133. 1 interaction.
STRINGP01133.

PTM databases

PhosphoSiteP01133.

Proteomic databases

PRIDEP01133.

Genome annotation databases

EnsemblENST00000265171; ENSP00000265171; ENSG00000138798; Homo sapiens. [Genome view]
GeneID1950.
KEGGhsa:1950.
UCSCuc003hzy.2. human.

Organism-specific databases

CTD1950.
GeneCardsGC04P111104.
H-InvDBHIX0031420.
HGNCHGNC:3229. EGF.
HPACAB017843.
MIM131530. gene.
611718. phenotype.
PharmGKBPA27664.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG06050.
HOGENOMHBG279909.
HOVERGENP01133.
InParanoidP01133.
OMAANSQDIR.
OrthoDBEOG9T7BPR.

Enzyme and pathway databases

Pathway_Interaction_DBa6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
arf6cyclingpathway. Arf6 signaling events.
ceramidepathway. Ceramide signaling pathway.
endothelinpathway. Endothelins.
telomerasepathway. Regulation of Telomerase.
ptp1bpathway. Signaling events mediated by PTP1B.
txa2pathway. Thromboxane A2 receptor signaling.
ReactomeREACT_604. Hemostasis.
REACT_9417. Signaling by EGFR.

Gene expression databases

ArrayExpressP01133.
BgeeP01133.
CleanExHS_EGF.
GenevestigatorP01133.

Family and domain databases

InterProIPR011042. 6-blade_b-propeller_TolB-like.
IPR006210. EGF-like.
IPR013032. EGF-like_reg_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR001336. EGF_1.
IPR000742. EGF_3.
IPR001881. EGF_Ca_bd.
IPR013091. EGF_Ca_bd_2.
IPR018097. EGF_Ca_bd_CS.
IPR000033. LDL_rcpt_classB_YWTD_rpt.
IPR016317. Pro-epidermal_GF.
[Graphical view]
Gene3DG3DSA:2.120.10.30. 6-blade_b-propeller_TolB-like. 2 hits.
PfamPF07645. EGF_CA. 3 hits.
PF00058. Ldl_recept_b. 4 hits.
[Graphical view]
PIRSFPIRSF001778. Pro-epidermal_growth_factor. 1 hit.
PRINTSPR00009. EGFTGF.
SMARTSM00181. EGF. 6 hits.
SM00179. EGF_CA. 2 hits.
SM00135. LY. 9 hits.
[Graphical view]
PROSITEPS00010. 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.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00605. Sulindac.
NextBio7903.
PMAP-CutDBP01133.
SOURCESearch...

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Entry information

Entry nameEGF_HUMAN
AccessionPrimary (citable) accession number: P01133
Secondary accession number(s): Q52LZ6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 7, 2009
Last modified: February 9, 2010
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents