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Protein

Proepiregulin

Gene

EREG

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

Functioni

Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR and ERBB4 tyrosine phosphorylation (PubMed:9419975). 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

GO - Biological processi

  • anatomical structure morphogenesis Source: UniProtKB
  • angiogenesis Source: UniProtKB-KW
  • animal organ morphogenesis Source: UniProtKB
  • cell-cell signaling Source: UniProtKB
  • cytokine-mediated signaling pathway Source: UniProtKB
  • epidermal growth factor receptor signaling pathway Source: UniProtKB
  • ERBB2 signaling pathway Source: Reactome
  • female meiotic nuclear division Source: UniProtKB
  • keratinocyte differentiation Source: UniProtKB
  • keratinocyte proliferation Source: UniProtKB
  • luteinizing hormone signaling pathway Source: UniProtKB
  • MAPK cascade Source: Reactome
  • mRNA transcription Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of epithelial 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 cell division Source: UniProtKB-KW
  • 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 protein kinase B signaling Source: Reactome
  • positive regulation of smooth muscle cell proliferation Source: UniProtKB
  • primary follicle stage Source: UniProtKB
  • regulation of cell motility Source: Reactome
  • response to peptide hormone Source: Ensembl
  • wound healing Source: UniProtKB

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-1227986 Signaling by ERBB2
R-HSA-1236394 Signaling by ERBB4
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1250342 PI3K events in ERBB4 signaling
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-1963642 PI3K events in ERBB2 signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
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-8863795 Downregulation of ERBB2 signaling
SIGNORiO14944

Names & Taxonomyi

Protein namesi
Recommended name:
Proepiregulin
Cleaved into the following chain:
Epiregulin
Short name:
EPR
Gene namesi
Name:EREG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000124882.3
HGNCiHGNC:3443 EREG
MIMi602061 gene
neXtProtiNX_O14944

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 domaini60 – 119ExtracellularSequence analysisAdd BLAST60
Transmembranei120 – 140HelicalSequence analysisAdd BLAST21
Topological domaini141 – 169CytoplasmicSequence analysisAdd BLAST29

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi2069
OpenTargetsiENSG00000124882
PharmGKBiPA27856

Polymorphism and mutation databases

BioMutaiEREG

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
ChainiPRO_000030280030 – 169ProepiregulinAdd BLAST140
PropeptideiPRO_000000755630 – 62By similarityAdd BLAST33
ChainiPRO_000000755763 – 108EpiregulinAdd BLAST46
PropeptideiPRO_0000007558109 – 169Removed in mature formBy similarityAdd BLAST61

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi47N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi68 ↔ 81PROSITE-ProRule annotation1 Publication
Disulfide bondi76 ↔ 92PROSITE-ProRule annotation1 Publication
Disulfide bondi94 ↔ 103PROSITE-ProRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO14944
PaxDbiO14944
PeptideAtlasiO14944
PRIDEiO14944
ProteomicsDBi48327

PTM databases

iPTMnetiO14944
PhosphoSitePlusiO14944

Expressioni

Tissue specificityi

In normal adults, expressed predominantly in the placenta and peripheral blood leukocytes. High levels were detected in carcinomas of the bladder, lung, kidney and colon.1 Publication

Gene expression databases

BgeeiENSG00000124882
CleanExiHS_EREG
GenevisibleiO14944 HS

Organism-specific databases

HPAiHPA054373

Interactioni

Subunit structurei

Interacts with EGFR and ERBB4.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108381, 5 interactors
STRINGi9606.ENSP00000244869

Structurei

Secondary structure

1169
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi65 – 67Combined sources3
Helixi70 – 72Combined sources3
Turni73 – 75Combined sources3
Beta strandi79 – 84Combined sources6
Turni85 – 88Combined sources4
Beta strandi89 – 94Combined sources6
Beta strandi98 – 100Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K36NMR-A63-108[»]
1K37NMR-A63-108[»]
5E8DX-ray2.50A38-108[»]
5WB7X-ray2.94E/F/G/H56-116[»]
ProteinModelPortaliO14944
SMRiO14944
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14944

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini64 – 104EGF-likePROSITE-ProRule annotationAdd BLAST41

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi145 – 152Arg/Lys-rich (basic)8

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IXV0 Eukaryota
ENOG410YNFA LUCA
GeneTreeiENSGT00510000048748
HOGENOMiHOG000059635
HOVERGENiHBG005601
InParanoidiO14944
KOiK09784
OMAiRCEHFFL
OrthoDBiEOG091G0SX3
PhylomeDBiO14944
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.

O14944-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAGRRMEML CAGRVPALLL CLGFHLLQAV LSTTVIPSCI PGESSDNCTA
60 70 80 90 100
LVQTEDNPRV AQVSITKCSS DMNGYCLHGQ CIYLVDMSQN YCRCEVGYTG
110 120 130 140 150
VRCEHFFLTV HQPLSKEYVA LTVILIILFL ITVVGSTYYF CRWYRNRKSK
160
EPKKEYERVT SGDPELPQV
Length:169
Mass (Da):19,044
Last modified:January 1, 1998 - v1
Checksum:i17F3926ADFB2BDEE
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03583342G → A in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_033827147R → Q. Corresponds to variant dbSNP:rs35275884Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D30783 mRNA Translation: BAA22146.1
AK314959 mRNA Translation: BAG37463.1
CR541887 mRNA Translation: CAG46685.1
CH471057 Genomic DNA Translation: EAX05709.1
BC136404 mRNA Translation: AAI36405.1
BC136405 mRNA Translation: AAI36406.1
CCDSiCCDS3564.1
RefSeqiNP_001423.1, NM_001432.2
UniGeneiHs.115263

Genome annotation databases

EnsembliENST00000244869; ENSP00000244869; ENSG00000124882
GeneIDi2069
KEGGihsa:2069
UCSCiuc003hie.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiEREG_HUMAN
AccessioniPrimary (citable) accession number: O14944
Secondary accession number(s): B2RC66, Q6FH69
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: June 20, 2018
This is version 169 of the entry and version 1 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, Reference proteome

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