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Protein

Proheparin-binding EGF-like growth factor

Gene

Hbegf

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4. Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor (By similarity).By similarity

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: RGD
  • growth factor activity Source: RGD
  • heparin binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Keywords - Ligandi

Heparin-binding

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-2179392. EGFR Transactivation by Gastrin.
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-8857538. PTK6 promotes HIF1A stabilization.

Names & Taxonomyi

Protein namesi
Recommended name:
Proheparin-binding EGF-like growth factor
Cleaved into the following chain:
Heparin-binding EGF-like growth factor
Short name:
HB-EGF
Short name:
HBEGF
Gene namesi
Name:Hbegf
Synonyms:Dtr, Hegfl
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 18

Organism-specific databases

RGDi2526. Hbegf.

Subcellular locationi

Heparin-binding EGF-like growth factor :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 160137ExtracellularSequence analysisAdd
BLAST
Transmembranei161 – 18424HelicalSequence analysisAdd
BLAST
Topological domaini185 – 20824CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence analysisAdd
BLAST
Chaini24 – 208185Proheparin-binding EGF-like growth factorPRO_0000302806Add
BLAST
Propeptidei24 – 6239By similarityPRO_0000007620Add
BLAST
Chaini63 – 14886Heparin-binding EGF-like growth factorPRO_0000007621Add
BLAST
Propeptidei149 – 20860C-terminalSequence analysisPRO_0000007622Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi85 – 851O-linked (GalNAc...)By similarity
Disulfide bondi108 ↔ 121PROSITE-ProRule annotation
Disulfide bondi116 ↔ 132PROSITE-ProRule annotation
Disulfide bondi134 ↔ 143PROSITE-ProRule annotation

Post-translational modificationi

O-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ06175.
PRIDEiQ06175.

Expressioni

Tissue specificityi

Most abundant in skeletal muscle, lung, spleen brain and heart.1 Publication

Gene expression databases

GenevisibleiQ06175. RN.

Interactioni

Subunit structurei

Interacts with FBLN1. Interacts with EGFR and ERBB4 (By similarity).By similarity

GO - Molecular functioni

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025157.

Structurei

3D structure databases

ProteinModelPortaliQ06175.
SMRiQ06175. Positions 107-147.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini104 – 14441EGF-likePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 EGF-like domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IMHM. Eukaryota.
ENOG41120D3. LUCA.
GeneTreeiENSGT00530000063708.
HOGENOMiHOG000026782.
HOVERGENiHBG053952.
InParanoidiQ06175.
KOiK08523.
OMAiYSYDHTT.
OrthoDBiEOG7VQJGP.
PhylomeDBiQ06175.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PfamiPF12661. hEGF. 1 hit.
[Graphical view]
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.

Q06175-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKLLPSVVLK LFLAAVLSAL VTGESLERLR RGLAAATSNP DPPTGTTNQL
60 70 80 90 100
LPTGADRAQE VQDLEGTDLD LFKVAFSSKP QALATPGKEK NGKKKRKGKG
110 120 130 140 150
LGKKRDPCLK KYKDYCIHGE CRYLKELRIP SCHCLPGYHG QRCHGLTLPV
160 170 180 190 200
ENPLYTYDHT TVLAVVAVVL SSVCLLVIVG LLMFRYHRRG GYDLESEEKV

KLGMASSH
Length:208
Mass (Da):22,843
Last modified:February 1, 1995 - v1
Checksum:iDDBD045E116D064C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L05489 mRNA. Translation: AAA81780.1.
PIRiJC1409.
RefSeqiNP_037077.1. NM_012945.1.
UniGeneiRn.10148.

Genome annotation databases

EnsembliENSRNOT00000025157; ENSRNOP00000025157; ENSRNOG00000018646.
GeneIDi25433.
KEGGirno:25433.
UCSCiRGD:2526. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L05489 mRNA. Translation: AAA81780.1.
PIRiJC1409.
RefSeqiNP_037077.1. NM_012945.1.
UniGeneiRn.10148.

3D structure databases

ProteinModelPortaliQ06175.
SMRiQ06175. Positions 107-147.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025157.

Proteomic databases

PaxDbiQ06175.
PRIDEiQ06175.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000025157; ENSRNOP00000025157; ENSRNOG00000018646.
GeneIDi25433.
KEGGirno:25433.
UCSCiRGD:2526. rat.

Organism-specific databases

CTDi1839.
RGDi2526. Hbegf.

Phylogenomic databases

eggNOGiENOG410IMHM. Eukaryota.
ENOG41120D3. LUCA.
GeneTreeiENSGT00530000063708.
HOGENOMiHOG000026782.
HOVERGENiHBG053952.
InParanoidiQ06175.
KOiK08523.
OMAiYSYDHTT.
OrthoDBiEOG7VQJGP.
PhylomeDBiQ06175.

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-2179392. EGFR Transactivation by Gastrin.
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-8857538. PTK6 promotes HIF1A stabilization.

Miscellaneous databases

PROiQ06175.

Gene expression databases

GenevisibleiQ06175. RN.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PfamiPF12661. hEGF. 1 hit.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Heparin-binding EGF-like growth factor: characterization of rat and mouse cDNA clones, protein domain conservation across species, and transcript expression in tissues."
    Abraham J.A., Damm D., Bajardi A., Miller J., Klagsbrun M., Ezekowitz R.A.B.
    Biochem. Biophys. Res. Commun. 190:125-133(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
    Tissue: Macrophage.

Entry informationi

Entry nameiHBEGF_RAT
AccessioniPrimary (citable) accession number: Q06175
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 6, 2016
This is version 119 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, Reference proteome

Documents

  1. 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.