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Protein

Proepiregulin

Gene

Ereg

Organism
Rattus norvegicus (Rat)
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 (PubMed:9990076). Contributes to inflammation, wound healing, tissue repair, and oocyte maturation by regulating angiogenesis and vascular remodeling and by stimulating cell proliferation (PubMed:24631357).1 Publication1 Publication

GO - Molecular functioni

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

GO - Biological processi

  • angiogenesis Source: UniProtKB-KW
  • cell-cell signaling Source: UniProtKB
  • cell proliferation Source: RGD
  • cytokine-mediated signaling pathway Source: UniProtKB
  • epidermal growth factor receptor signaling pathway Source: UniProtKB
  • female meiotic nuclear 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
  • ovarian cumulus expansion Source: UniProtKB
  • ovulation Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of cell proliferation Source: RGD
  • 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: RGD

Keywordsi

Molecular functionDevelopmental protein, Growth factor, Mitogen
Biological processAngiogenesis, Differentiation

Enzyme and pathway databases

ReactomeiR-RNO-1227986. Signaling by ERBB2.
R-RNO-1236394. Signaling by ERBB4.
R-RNO-1250196. SHC1 events in ERBB2 signaling.
R-RNO-1250342. PI3K events in ERBB4 signaling.
R-RNO-1250347. SHC1 events in ERBB4 signaling.
R-RNO-1257604. PIP3 activates AKT signaling.
R-RNO-1963640. GRB2 events in ERBB2 signaling.
R-RNO-1963642. PI3K events in ERBB2 signaling.
R-RNO-5673001. RAF/MAP kinase cascade.
R-RNO-6785631. ERBB2 Regulates Cell Motility.
R-RNO-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-RNO-8847993. ERBB2 Activates PTK6 Signaling.
R-RNO-8863795. Downregulation of ERBB2 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Proepiregulin
Cleaved into the following chain:
Epiregulin
Short name:
EPR
Gene namesi
Name:Ereg
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 14

Organism-specific databases

RGDi620299. 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)DescriptionActionsGraphical viewLength
Transmembranei113 – 133HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

  • extracellular space Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_500005471023 – 162ProepiregulinAdd BLAST140
PropeptideiPRO_000043396023 – 551 PublicationAdd BLAST33
ChainiPRO_500005471156 – 101EpiregulinAdd BLAST46
PropeptideiPRO_0000433961102 – 162Removed in mature formBy similarityAdd BLAST61

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi40N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi61 ↔ 74PROSITE-ProRule annotation
Disulfide bondi69 ↔ 85PROSITE-ProRule annotation
Disulfide bondi87 ↔ 96PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9Z0L5.

PTM databases

PhosphoSitePlusiQ9Z0L5.

Expressioni

Inductioni

By angiotensin II, endothelin-1 and alpha-thrombin. Strongly induced in ovarian granulosa cells by FSH stimulation.2 Publications

Gene expression databases

BgeeiENSRNOG00000002771.
GenevisibleiQ9Z0L5. RN.

Interactioni

Subunit structurei

Interacts with EGFR and ERBB4.By similarity

GO - Molecular functioni

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000003716.

Structurei

3D structure databases

ProteinModelPortaliQ9Z0L5.
SMRiQ9Z0L5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini57 – 97EGF-likePROSITE-ProRule annotationAdd BLAST41

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IXV0. Eukaryota.
ENOG410YNFA. LUCA.
GeneTreeiENSGT00510000048748.
HOGENOMiHOG000059635.
HOVERGENiHBG005601.
KOiK09784.
OMAiRCEHFFL.
OrthoDBiEOG091G0SX3.
PhylomeDBiQ9Z0L5.
TreeFamiTF336145.

Family and domain databases

InterProiView protein in InterPro
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
PANTHERiPTHR10740. PTHR10740. 1 hit.
PROSITEiView protein in PROSITE
PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q9Z0L5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METFPAAWVL ALLCLGSHLL QAVISTTVIP SCIPEESEDN CTALVQMEDD
60 70 80 90 100
PRVAQVLITK CSSDMDGYCL HGHCIYLVDM SEKYCRCEVG YTGLRCEHFF
110 120 130 140 150
LTVHQPLSRE YVALTVILVF LFLIVTAGSM YYFCRWYRNR KSKKSREEYE
160
RVTSGGPGLP QV
Length:162
Mass (Da):18,404
Last modified:May 1, 1999 - v1
Checksum:iEA660DE2B34990C4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF074952 mRNA. Translation: AAD10631.1.
AB078739 Genomic DNA. Translation: BAC44880.1.
AABR07072382 Genomic DNA. No translation available.
AC108576 Genomic DNA. No translation available.
CH474060 Genomic DNA. Translation: EDL88580.1.
RefSeqiNP_067721.1. NM_021689.1.
UniGeneiRn.42897.

Genome annotation databases

EnsembliENSRNOT00000003716; ENSRNOP00000003716; ENSRNOG00000002771.
GeneIDi59325.
KEGGirno:59325.
UCSCiRGD:620299. rat.

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.

Entry informationi

Entry nameiEREG_RAT
AccessioniPrimary (citable) accession number: Q9Z0L5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 14, 2015
Last sequence update: May 1, 1999
Last modified: June 7, 2017
This is version 134 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome