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Protein

Proepiregulin

Gene

Ereg

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR and ERBB4 tyrosine phosphorylation (By similarity). Contributes to inflammation, wound healing, tissue repair, and oocyte maturation by regulating angiogenesis and vascular remodeling and by stimulating cell proliferation (PubMed:24631357).1 PublicationBy similarity

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: UniProtKB
  • growth factor activity Source: GO_Central

GO - Biological processi

  • anatomical structure morphogenesis Source: UniProtKB
  • angiogenesis Source: UniProtKB-KW
  • cell-cell signaling Source: UniProtKB
  • cytokine-mediated signaling pathway Source: UniProtKB
  • epidermal growth factor receptor signaling pathway Source: UniProtKB
  • female meiotic division Source: UniProtKB
  • keratinocyte proliferation Source: UniProtKB
  • luteinizing hormone signaling pathway Source: UniProtKB
  • mRNA transcription Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of smooth muscle cell differentiation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • oocyte maturation Source: UniProtKB
  • organ morphogenesis Source: UniProtKB
  • ovarian cumulus expansion Source: UniProtKB
  • ovulation Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of cytokine biosynthetic process Source: UniProtKB
  • positive regulation of cytokine production Source: UniProtKB
  • positive regulation of DNA replication Source: UniProtKB
  • positive regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
  • positive regulation of fibroblast proliferation Source: UniProtKB
  • positive regulation of innate immune response Source: UniProtKB
  • positive regulation of interleukin-6 biosynthetic process Source: UniProtKB
  • positive regulation of mitotic nuclear division Source: UniProtKB
  • positive regulation of phosphorylation Source: UniProtKB
  • positive regulation of protein kinase activity Source: UniProtKB
  • positive regulation of smooth muscle cell proliferation Source: UniProtKB
  • primary follicle stage Source: UniProtKB
  • response to peptide hormone Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Keywords - Biological processi

Angiogenesis, Differentiation

Enzyme and pathway databases

ReactomeiR-MMU-1227986. Signaling by ERBB2.
R-MMU-1236394. Signaling by ERBB4.
R-MMU-1250196. SHC1 events in ERBB2 signaling.
R-MMU-1250342. PI3K events in ERBB4 signaling.
R-MMU-1250347. SHC1 events in ERBB4 signaling.
R-MMU-1257604. PIP3 activates AKT signaling.
R-MMU-1963640. GRB2 events in ERBB2 signaling.
R-MMU-1963642. PI3K events in ERBB2 signaling.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-6785631. ERBB2 Regulates Cell Motility.
R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-MMU-8847993. ERBB2 Activates PTK6 Signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Proepiregulin
Cleaved into the following chain:
Epiregulin
Short name:
EPR
Gene namesi
Name:Ereg
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:107508. Ereg.

Subcellular locationi

Epiregulin :
  • Secretedextracellular space By similarity
Proepiregulin :
  • Cell membrane By similarity; Single-pass type I membrane protein By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini53 – 11260ExtracellularSequence analysisAdd
BLAST
Transmembranei113 – 13321HelicalSequence analysisAdd
BLAST
Topological domaini134 – 16229CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • extracellular space Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence analysisAdd
BLAST
Chaini23 – 162140ProepiregulinPRO_0000302801Add
BLAST
Propeptidei23 – 55331 PublicationPRO_0000007559Add
BLAST
Chaini56 – 10146EpiregulinPRO_0000007560Add
BLAST
Propeptidei102 – 16261Removed in mature formBy similarityPRO_0000007561Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi40 – 401N-linked (GlcNAc...)Sequence analysis
Disulfide bondi61 ↔ 74PROSITE-ProRule annotation
Disulfide bondi69 ↔ 85PROSITE-ProRule annotation
Disulfide bondi87 ↔ 96PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ61521.
PRIDEiQ61521.

Miscellaneous databases

PMAP-CutDBQ61521.

Expressioni

Developmental stagei

Expressed in 7-day-old embryos with levels then falling to very low or undetectable amounts. Not detected in adult.1 Publication

Gene expression databases

BgeeiQ61521.
CleanExiMM_EREG.
GenevisibleiQ61521. MM.

Interactioni

Subunit structurei

Interacts with EGFR and ERBB4.By similarity

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: UniProtKB
  • growth factor activity Source: GO_Central

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000031324.

Structurei

3D structure databases

ProteinModelPortaliQ61521.
SMRiQ61521. Positions 56-101.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini57 – 9741EGF-likePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi138 – 1458Arg/Lys-rich (basic)

Sequence similaritiesi

Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IXV0. Eukaryota.
ENOG410YNFA. LUCA.
GeneTreeiENSGT00510000048748.
HOGENOMiHOG000059635.
HOVERGENiHBG005601.
InParanoidiQ61521.
KOiK09784.
OMAiESEDNCT.
OrthoDBiEOG7JT6XP.
PhylomeDBiQ61521.
TreeFamiTF336145.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q61521-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METLPASWVL TLLCLGSHLL QAVISTTVIP SCIPGESEDN CTALVQMEDD
60 70 80 90 100
PRVAQVQITK CSSDMDGYCL HGQCIYLVDM REKFCRCEVG YTGLRCEHFF
110 120 130 140 150
LTVHQPLSKE YVALTVILIF LFLIITAGCI YYFCRWYKNR KSKKSREEYE
160
RVTSGDPVLP QV
Length:162
Mass (Da):18,474
Last modified:November 1, 1996 - v1
Checksum:iDA50A10C9386B97D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D30782 mRNA. Translation: BAA06446.1.
BC027838 mRNA. Translation: AAH27838.1.
CCDSiCCDS19420.1.
PIRiJT0747.
S68401.
RefSeqiNP_031976.1. NM_007950.2.
UniGeneiMm.4791.

Genome annotation databases

EnsembliENSMUST00000031324; ENSMUSP00000031324; ENSMUSG00000029377.
GeneIDi13874.
KEGGimmu:13874.
UCSCiuc008ybs.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D30782 mRNA. Translation: BAA06446.1.
BC027838 mRNA. Translation: AAH27838.1.
CCDSiCCDS19420.1.
PIRiJT0747.
S68401.
RefSeqiNP_031976.1. NM_007950.2.
UniGeneiMm.4791.

3D structure databases

ProteinModelPortaliQ61521.
SMRiQ61521. Positions 56-101.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000031324.

Proteomic databases

PaxDbiQ61521.
PRIDEiQ61521.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000031324; ENSMUSP00000031324; ENSMUSG00000029377.
GeneIDi13874.
KEGGimmu:13874.
UCSCiuc008ybs.1. mouse.

Organism-specific databases

CTDi2069.
MGIiMGI:107508. Ereg.

Phylogenomic databases

eggNOGiENOG410IXV0. Eukaryota.
ENOG410YNFA. LUCA.
GeneTreeiENSGT00510000048748.
HOGENOMiHOG000059635.
HOVERGENiHBG005601.
InParanoidiQ61521.
KOiK09784.
OMAiESEDNCT.
OrthoDBiEOG7JT6XP.
PhylomeDBiQ61521.
TreeFamiTF336145.

Enzyme and pathway databases

ReactomeiR-MMU-1227986. Signaling by ERBB2.
R-MMU-1236394. Signaling by ERBB4.
R-MMU-1250196. SHC1 events in ERBB2 signaling.
R-MMU-1250342. PI3K events in ERBB4 signaling.
R-MMU-1250347. SHC1 events in ERBB4 signaling.
R-MMU-1257604. PIP3 activates AKT signaling.
R-MMU-1963640. GRB2 events in ERBB2 signaling.
R-MMU-1963642. PI3K events in ERBB2 signaling.
R-MMU-5673001. RAF/MAP kinase cascade.
R-MMU-6785631. ERBB2 Regulates Cell Motility.
R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-MMU-8847993. ERBB2 Activates PTK6 Signaling.

Miscellaneous databases

PMAP-CutDBQ61521.
PROiQ61521.
SOURCEiSearch...

Gene expression databases

BgeeiQ61521.
CleanExiMM_EREG.
GenevisibleiQ61521. MM.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of mouse epiregulin, a novel epidermal growth factor-related protein, expressed in the early stage of development."
    Toyoda H., Komurasaki T., Ikeda Y., Yoshimoto M., Morimoto S.
    FEBS Lett. 377:403-407(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
    Strain: NIH Swiss.
    Tissue: Fibroblast.
  2. "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].
  3. "Epiregulin, a novel epidermal growth factor with mitogenic activity for rat primary hepatocytes."
    Toyoda H., Komurasaki T., Uchida D., Takayama Y., Isobe T., Okuyama T., Hanada K.
    J. Biol. Chem. 270:7495-7500(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 56-101.
  4. "Epiregulin: roles in normal physiology and cancer."
    Riese D.J. II, Cullum R.L.
    Semin. Cell Dev. Biol. 28:49-56(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiEREG_MOUSE
AccessioniPrimary (citable) accession number: Q61521
Secondary accession number(s): Q7M0A8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: November 1, 1996
Last modified: July 6, 2016
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.