P01132 (EGF_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pro-epidermal growth factor
Short name=EGF

Cleaved into the following chain:

1. Epidermal growth factor

Gene names

Name:

Egf

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1217 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

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 By similarity.
Subunit structure	Interacts with EGFR and promotes EGFR dimerization. Interacts with RHBDF1; may retain EGF in the endoplasmic reticulum and regulates its degradation through the endoplasmic reticulum-associated degradation (ERAD). Interacts with RHBDF2. Ref.7
Subcellular location	Membrane; Single-pass type I membrane protein.
Sequence similarities	Contains 9 EGF-like domains. Contains 8 LDL-receptor class B repeats.
Sequence caution	The sequence CAA24115.1 differs from that shown. Reason: Frameshift at positions 1134 and 1168.

Ontologies

Keywords
Cellular component	Membrane
Domain	EGF-like domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara STAT protein import into nucleus Inferred from direct assay PubMed 15156153. Source: UniProtKB activation of MAPKK activity Inferred from direct assay PubMed 16339969. Source: MGI angiogenesis Inferred from electronic annotation. Source: Compara branching morphogenesis of an epithelial tube Inferred from direct assay PubMed 15831470. Source: MGI epidermal growth factor receptor signaling pathway Inferred from direct assay PubMed 15695332PubMed 6315706. Source: MGI mammary gland alveolus development Inferred from genetic interaction PubMed 10331984. Source: MGI negative regulation of cholesterol efflux Inferred from direct assay PubMed 20037141. Source: BHF-UCL negative regulation of secretion Inferred from electronic annotation. Source: Compara peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 14561752. Source: MGI positive regulation of DNA binding Inferred from direct assay PubMed 15156153. Source: UniProtKB 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 cerebellar granule cell precursor proliferation Inferred from direct assay PubMed 10027293. Source: MGI positive regulation of epidermal growth factor-activated receptor activity Inferred from electronic annotation. Source: Compara positive regulation of hyaluronan biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of mitosis Inferred from electronic annotation. Source: Compara positive regulation of peptidyl-threonine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from direct assay PubMed 20208556. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara regulation of calcium ion import Inferred from electronic annotation. Source: Compara regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 11940581. Source: MGI regulation of protein localization to cell surface Inferred from electronic annotation. Source: Compara regulation of protein transport Inferred from sequence orthology PubMed 19723622. Source: MGI
Cellular_component	extracellular space Inferred from direct assay PubMed 7641815PubMed 8240367. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay PubMed 17626015. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro epidermal growth factor receptor binding Inferred from direct assay PubMed 6315706. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Potential

Chain

29 – 1217

1189

Pro-epidermal growth factor

PRO_0000007542

Chain

977 – 1029

53

Epidermal growth factor Ref.5

PRO_0000007543

Regions

Topological domain

29 – 1038

1010

Extracellular Potential

Transmembrane

1039 – 1058

20

Helical; Potential

Topological domain

1059 – 1217

159

Cytoplasmic Potential

Repeat

93 – 134

42

LDL-receptor class B 1

Repeat

135 – 176

42

LDL-receptor class B 2

Repeat

177 – 219

43

LDL-receptor class B 3

Domain

327 – 361

35

EGF-like 1; incomplete

Domain

362 – 402

41

EGF-like 2; calcium-binding Potential

Domain

403 – 443

41

EGF-like 3

Domain

441 – 483

43

EGF-like 4

Repeat

489 – 529

41

LDL-receptor class B 4

Repeat

530 – 572

43

LDL-receptor class B 5

Repeat

573 – 615

43

LDL-receptor class B 6

Repeat

616 – 659

44

LDL-receptor class B 7

Repeat

660 – 702

43

LDL-receptor class B 8

Domain

747 – 787

41

EGF-like 5

Domain

838 – 876

39

EGF-like 6

Domain

877 – 918

42

EGF-like 7; calcium-binding Potential

Domain

919 – 959

41

EGF-like 8; calcium-binding Potential

Domain

978 – 1019

42

EGF-like 9

Region

1024 – 1029

6

Not required for full biological activity

Amino acid modifications

Glycosylation

111

1

N-linked (GlcNAc...) Potential

Glycosylation

410

1

N-linked (GlcNAc...) Potential

Glycosylation

810

1

N-linked (GlcNAc...) Potential

Glycosylation

944

1

N-linked (GlcNAc...) Potential

Disulfide bond

366 ↔ 377

By similarity

Disulfide bond

373 ↔ 386

By similarity

Disulfide bond

388 ↔ 401

By similarity

Disulfide bond

407 ↔ 418

By similarity

Disulfide bond

414 ↔ 427

By similarity

Disulfide bond

429 ↔ 442

By similarity

Disulfide bond

445 ↔ 457

By similarity

Disulfide bond

453 ↔ 467

By similarity

Disulfide bond

469 ↔ 482

By similarity

Disulfide bond

751 ↔ 762

By similarity

Disulfide bond

758 ↔ 771

By similarity

Disulfide bond

773 ↔ 786

By similarity

Disulfide bond

842 ↔ 853

By similarity

Disulfide bond

847 ↔ 862

By similarity

Disulfide bond

864 ↔ 875

By similarity

Disulfide bond

881 ↔ 895

By similarity

Disulfide bond

888 ↔ 904

By similarity

Disulfide bond

906 ↔ 917

By similarity

Disulfide bond

923 ↔ 936

By similarity

Disulfide bond

930 ↔ 945

By similarity

Disulfide bond

947 ↔ 958

By similarity

Disulfide bond

982 ↔ 996

Ref.6

Disulfide bond

990 ↔ 1007

Ref.6

Disulfide bond

1009 ↔ 1018

Ref.6

Experimental info

Sequence conflict

790

1

D → Y in CAA24115. Ref.2

Sequence conflict

931

1

G → A in AAA37539. Ref.1

Sequence conflict

931

1

G → A in CAA24115. Ref.2

Sequence conflict

931

1

G → A in AAH60741. Ref.4

Sequence conflict

931

1

G → A in AAH92277. Ref.4

Sequence conflict

956

1

L → R in AAA37539. Ref.1

Sequence conflict

956

1

L → R in CAA24115. Ref.2

Sequence conflict

956

1

L → R in AAH60741. Ref.4

Sequence conflict

956

1

L → R in AAH92277. Ref.4

Sequence conflict

1048

1

A → S in CAA24115. Ref.2

Sequence conflict

1054

1

V → L in AAA37539. Ref.1

Sequence conflict

1054

1

V → L in CAA24115. Ref.2

Sequence conflict

1054

1

V → L in AAH60741. Ref.4

Sequence conflict

1054

1

V → L in AAH92277. Ref.4

Sequence conflict

1090

1

N → D in AAA37539. Ref.1

Sequence conflict

1090

1

N → D in CAA24115. Ref.2

Sequence conflict

1090

1

N → D in AAH60741. Ref.4

Sequence conflict

1090

1

N → D in AAH92277. Ref.4

Sequence conflict

1217

1

Q → K in AAA37539. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

1217

Helix Strand Turn

Details...

Beta strand

987 – 990

4

Beta strand

991 – 993

3

Beta strand

995 – 998

4

Turn

1000 – 1002

3

Beta strand

1003 – 1008

6

Turn

1015 – 1017

3

Beta strand

1023 – 1026

4

Sequences

	Sequence		Length	Mass (Da)
	P01132 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 28F35C928280D31B	FASTA	1,217	133,072
	10 20 30 40 50 60 MPWGRRPTWL LLAFLLVFLK ISILSVTAWQ TGNCQPGPLE RSERSGTCAG PAPFLVFSQG 70 80 90 100 110 120 KSISRIDPDG TNHQQLVVDA GISADMDIHY KKERLYWVDV ERQVLLRVFL NGTGLEKVCN 130 140 150 160 170 180 VERKVSGLAI DWIDDEVLWV DQQNGVITVT DMTGKNSRVL LSSLKHPSNI AVDPIERLMF 190 200 210 220 230 240 WSSEVTGSLH RAHLKGVDVK TLLETGGISV LTLDVLDKRL FWVQDSGEGS HAYIHSCDYE 250 260 270 280 290 300 GGSVRLIRHQ ARHSLSSMAF FGDRIFYSVL KSKAIWIANK HTGKDTVRIN LHPSFVTPGK 310 320 330 340 350 360 LMVVHPRAQP RTEDAAKDPD PELLKQRGRP CRFGLCERDP KSHSSACAEG YTLSRDRKYC 370 380 390 400 410 420 EDVNECATQN HGCTLGCENT PGSYHCTCPT GFVLLPDGKQ CHELVSCPGN VSKCSHGCVL 430 440 450 460 470 480 TSDGPRCICP AGSVLGRDGK TCTGCSSPDN GGCSQICLPL RPGSWECDCF PGYDLQSDRK 490 500 510 520 530 540 SCAASGPQPL LLFANSQDIR HMHFDGTDYK VLLSRQMGMV FALDYDPVES KIYFAQTALK 550 560 570 580 590 600 WIERANMDGS QRERLITEGV DTLEGLALDW IGRRIYWTDS GKSVVGGSDL SGKHHRIIIQ 610 620 630 640 650 660 ERISRPRGIA VHPRARRLFW TDVGMSPRIE SASLQGSDRV LIASSNLLEP SGITIDYLTD 670 680 690 700 710 720 TLYWCDTKRS VIEMANLDGS KRRRLIQNDV GHPFSLAVFE DHLWVSDWAI PSVIRVNKRT 730 740 750 760 770 780 GQNRVRLQGS MLKPSSLVVV HPLAKPGADP CLYRNGGCEH ICQESLGTAR CLCREGFVKA 790 800 810 820 830 840 WDGKMCLPQD YPILSGENAD LSKEVTSLSN STQAEVPDDD GTESSTLVAE IMVSGMNYED 850 860 870 880 890 900 DCGPGGCGSH ARCVSDGETA ECQCLKGFAR DGNLCSDIDE CVLARSDCPS TSSRCINTEG 910 920 930 940 950 960 GYVCRCSEGY EGDGISCFDI DECQRGAHNC GENAACTNTE GGYNCTCAGR PSSPGLSCPD 970 980 990 1000 1010 1020 STAPSLLGED GHHLDRNSYP GCPSSYDGYC LNGGVCMHIE SLDSYTCNCV IGYSGDRCQT 1030 1040 1050 1060 1070 1080 RDLRWWELRH AGYGQKHDIM VVAVCMVALV LLLVLGMWGT YYYRTRKQLS NPPKNPCDEP 1090 1100 1110 1120 1130 1140 SGSVSSSGPN SSSGAAVASC PQPWFVVLEK HQDPKNGSLP ADGTNGAVVD AGLSPSLQLG 1150 1160 1170 1180 1190 1200 SVHLTSWRQK PHIDGMGTGQ SCWIPPSSDR GPQEIEGNSH LPSYRPVGPE KLHSLQSANG 1210 SCHERAPDLP RQTEPVQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of a mouse submaxillary messenger RNA encoding epidermal growth factor and seven related proteins." Scott J., Urdea M., Quiroga M., Sanchez-Pescador R., Fong N.M., Selby M., Rutter W.J., Bell G.I. Science 221:236-240(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor." Gray A., Dull T.J., Ullrich A. Nature 303:722-725(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Kidney and Salivary gland.
[5]	"The primary structure of epidermal growth factor." Savage C.R. Jr., Inagami T., Cohen S. J. Biol. Chem. 247:7612-7621(1972) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 977-1029.
[6]	"Epidermal growth factor. Location of disulfide bonds." Savage C.R. Jr., Hash J.H., Cohen S. J. Biol. Chem. 248:7669-7672(1973) [PubMed] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS.
[7]	"Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling." Zettl M., Adrain C., Strisovsky K., Lastun V., Freeman M. Cell 145:79-91(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RHBDF1 AND RHBDF2.
[8]	"Solution structure of murine epidermal growth factor determined by NMR spectroscopy and refined by energy minimization with restraints." Montelione G.T., Wuethrich K., Burgess A.W., Nice E.C., Wagner G., Gibson K.D., Scheraga H.A. Biochemistry 31:236-249(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 977-1029.
[9]	"Three-dimensional nuclear magnetic resonance structures of mouse epidermal growth factor in acidic and physiological pH solutions." Kohda D., Inagaki F. Biochemistry 31:11928-11939(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 977-1029.
[10]	"Role of the 6-20 disulfide bridge in the structure and activity of epidermal growth factor." Barnham K.J., Torres A.M., Alewood D., Alewood P.F., Domagala T., Nice E.C., Norton R.S. Protein Sci. 7:1738-1749(1998) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 980-1024.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J00380 mRNA. Translation: AAA37539.1.
V00741 mRNA. Translation: CAA24115.1. Frameshift.
V00741 mRNA. Translation: CAA24116.1.
AC098732 Genomic DNA. No translation available.
BC060741 mRNA. Translation: AAH60741.1.
BC092277 mRNA. Translation: AAH92277.1.

IPI

IPI00132121.

RefSeq

NP_034243.2. NM_010113.3.

UniGene

Mm.252481.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A3P	NMR	-	A	980-1024	[»]
1EGF	NMR	-	A	977-1029	[»]
1EPG	NMR	-	A	977-1029	[»]
1EPH	NMR	-	A	977-1029	[»]
1EPI	NMR	-	A	977-1029	[»]
1EPJ	NMR	-	A	977-1029	[»]
1GK5	NMR	-	A	977-1018	[»]
3EGF	NMR	-	A	977-1029	[»]

ProteinModelPortal

P01132.

SMR

P01132. Positions 51-779, 839-1029.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5762N.

IntAct

P01132. 4 interactions.

PTM databases

PhosphoSite

P01132.

Proteomic databases

PaxDb

P01132.

PRIDE

P01132.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000029653; ENSMUSP00000029653; ENSMUSG00000028017.

GeneID

13645.

KEGG

mmu:13645.

Organism-specific databases

CTD

1950.

MGI

MGI:95290. Egf.

Phylogenomic databases

eggNOG

NOG325841.

GeneTree

ENSGT00690000101695.

HOGENOM

HOG000112345.

HOVERGEN

HBG003858.

InParanoid

Q569W5.

KO

K04357.

OMA

VNECAFW.

OrthoDB

EOG480HVT.

Enzyme and pathway databases

Reactome

REACT_115202. Signal Transduction.
REACT_118324. Disease.

Gene expression databases

ArrayExpress

P01132.

Bgee

P01132.

CleanEx

MM_EGF.

Genevestigator

P01132.

GermOnline

ENSMUSG00000028017. Mus musculus.

Family and domain databases

Gene3D

2.120.10.30. 2 hits.

InterPro

IPR011042. 6-blade_b-propeller_TolB-like.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000033. LDLR_classB_rpt.
IPR016317. Pro-epidermal_GF.
[Graphical view]

Pfam

PF00008. EGF. 1 hit.
PF07645. EGF_CA. 3 hits.
PF00058. Ldl_recept_b. 3 hits.
[Graphical view]

PIRSF

PIRSF001778. Pro-epidermal_growth_factor. 1 hit.

SMART

SM00181. EGF. 5 hits.
SM00179. EGF_CA. 2 hits.
SM00135. LY. 9 hits.
[Graphical view]

PROSITE

PS00010. ASX_HYDROXYL. 3 hits.
PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 6 hits.
PS50026. EGF_3. 5 hits.
PS01187. EGF_CA. 3 hits.
PS51120. LDLRB. 8 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

EGF. mouse.

EvolutionaryTrace

P01132.

NextBio

284358.

PMAP-CutDB

P01132.

SOURCE

Search...

Entry information

Entry name

EGF_MOUSE

Accession

Primary (citable) accession number: P01132
Secondary accession number(s): E9QNX6, Q569W5, Q6P9J2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 155 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program