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Protein

Proepiregulin

Gene

EREG

Organism
Homo sapiens (Human)
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: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
  • 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 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
  • organ morphogenesis Source: UniProtKB
  • ovarian cumulus expansion Source: UniProtKB
  • ovulation Source: UniProtKB
  • phosphatidylinositol-mediated signaling Source: Reactome
  • 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
  • regulation of cell motility Source: Reactome
  • regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
  • response to peptide hormone Source: Ensembl
  • wound healing Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Growth factor, Mitogen

Keywords - Biological processi

Angiogenesis, 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.
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

HGNCiHGNC:3443. EREG.

Subcellular locationi

Epiregulin :
Proepiregulin :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini60 – 11960ExtracellularSequence analysisAdd
BLAST
Transmembranei120 – 14021HelicalSequence analysisAdd
BLAST
Topological domaini141 – 16929CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • intracellular Source: GOC
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27856.

Polymorphism and mutation databases

BioMutaiEREG.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929Sequence analysisAdd
BLAST
Chaini30 – 169140ProepiregulinPRO_0000302800Add
BLAST
Propeptidei30 – 6233By similarityPRO_0000007556Add
BLAST
Chaini63 – 10846EpiregulinPRO_0000007557Add
BLAST
Propeptidei109 – 16961Removed in mature formBy similarityPRO_0000007558Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi47 – 471N-linked (GlcNAc...)Sequence analysis
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.

PTM databases

iPTMnetiO14944.
PhosphoSiteiO14944.

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 interactions.
STRINGi9606.ENSP00000244869.

Structurei

Secondary structure

1
169
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi70 – 723Combined sources
Turni73 – 753Combined sources
Beta strandi79 – 846Combined sources
Turni85 – 884Combined sources
Beta strandi89 – 946Combined sources
Beta strandi98 – 1003Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1K36NMR-A63-108[»]
1K37NMR-A63-108[»]
5E8DX-ray2.50A38-108[»]
ProteinModelPortaliO14944.
SMRiO14944. Positions 63-108.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14944.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini64 – 10441EGF-likePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi145 – 1528Arg/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.
InParanoidiO14944.
KOiK09784.
OMAiRCEHFFL.
OrthoDBiEOG091G0SX3.
PhylomeDBiO14944.
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.

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti42 – 421G → A in a breast cancer sample; somatic mutation. 1 Publication
VAR_035833
Natural varianti147 – 1471R → Q.
Corresponds to variant rs35275884 [ dbSNP | Ensembl ].
VAR_033827

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1K36NMR-A63-108[»]
1K37NMR-A63-108[»]
5E8DX-ray2.50A38-108[»]
ProteinModelPortaliO14944.
SMRiO14944. Positions 63-108.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108381. 5 interactions.
STRINGi9606.ENSP00000244869.

PTM databases

iPTMnetiO14944.
PhosphoSiteiO14944.

Polymorphism and mutation databases

BioMutaiEREG.

Proteomic databases

MaxQBiO14944.
PaxDbiO14944.
PeptideAtlasiO14944.
PRIDEiO14944.

Protocols and materials databases

DNASUi2069.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2069.
GeneCardsiEREG.
HGNCiHGNC:3443. EREG.
HPAiHPA054373.
MIMi602061. gene.
neXtProtiNX_O14944.
PharmGKBiPA27856.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IXV0. Eukaryota.
ENOG410YNFA. LUCA.
GeneTreeiENSGT00510000048748.
HOGENOMiHOG000059635.
HOVERGENiHBG005601.
InParanoidiO14944.
KOiK09784.
OMAiRCEHFFL.
OrthoDBiEOG091G0SX3.
PhylomeDBiO14944.
TreeFamiTF336145.

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.
SIGNORiO14944.

Miscellaneous databases

EvolutionaryTraceiO14944.
GeneWikiiEpiregulin.
GenomeRNAii2069.
PROiO14944.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124882.
CleanExiHS_EREG.
GenevisibleiO14944. HS.

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...

Entry informationi

Entry nameiEREG_HUMAN
AccessioniPrimary (citable) accession number: O14944
Secondary accession number(s): B2RC66, Q6FH69
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: September 7, 2016
This is version 156 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.