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Protein

Proheparin-binding EGF-like growth factor

Gene

Hbegf

Organism
Mus musculus (Mouse)
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.

GO - Molecular functioni

  1. epidermal growth factor receptor binding Source: UniProtKB
  2. growth factor activity Source: UniProtKB
  3. heparin binding Source: UniProtKB

GO - Biological processi

  1. angiogenesis Source: UniProtKB
  2. blastocyst growth Source: UniProtKB
  3. cell migration Source: UniProtKB
  4. epidermal growth factor receptor signaling pathway Source: MGI
  5. negative regulation of elastin biosynthetic process Source: Ensembl
  6. positive regulation of cell growth Source: Ensembl
  7. positive regulation of cell migration Source: MGI
  8. positive regulation of keratinocyte migration Source: UniProtKB
  9. positive regulation of protein kinase B signaling Source: MGI
  10. positive regulation of smooth muscle cell proliferation Source: UniProtKB
  11. positive regulation of wound healing Source: MGI
  12. regulation of heart contraction Source: MGI
  13. wound healing, spreading of epidermal cells Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiREACT_188191. Signaling by ERBB2.
REACT_188528. GRB2 events in ERBB2 signaling.
REACT_188574. SHC1 events in ERBB2 signaling.
REACT_188579. Signaling by ERBB4.
REACT_188580. SHC1 events in ERBB4 signaling.
REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
REACT_198350. EGFR Transactivation by Gastrin.
REACT_198574. Nuclear signaling by ERBB4.
REACT_203296. PI3K events in ERBB4 signaling.
REACT_215348. PI3K events in ERBB2 signaling.
REACT_226341. PIP3 activates AKT signaling.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 18

Organism-specific databases

MGIiMGI:96070. Hbegf.

Subcellular locationi

Chain Heparin-binding EGF-like growth factor : Secretedextracellular space
Note: Mature HB-EGF is released into the extracellular space and probably binds to a receptor.

Topology

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

GO - Cellular componenti

  1. cell surface Source: MGI
  2. extracellular region Source: Reactome
  3. extracellular space Source: BHF-UCL
  4. integral component of plasma membrane Source: BHF-UCL
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_0000302804Add
BLAST
Propeptidei24 – 6239By similarityPRO_0000007614Add
BLAST
Chaini63 – 14886Heparin-binding EGF-like growth factorPRO_0000007615Add
BLAST
Propeptidei149 – 20860C-terminalSequence AnalysisPRO_0000007616Add
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

MaxQBiQ06186.
PRIDEiQ06186.

PTM databases

PhosphoSiteiQ06186.

Miscellaneous databases

PMAP-CutDBQ06186.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ06186.
CleanExiMM_HBEGF.
ExpressionAtlasiQ06186. baseline and differential.
GenevestigatoriQ06186.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025363.

Structurei

3D structure databases

ProteinModelPortaliQ06186.
SMRiQ06186. 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

eggNOGiNOG45526.
HOGENOMiHOG000026782.
HOVERGENiHBG053952.
InParanoidiQ06186.
KOiK08523.
OMAiYSYDHTT.
OrthoDBiEOG7VQJGP.
PhylomeDBiQ06186.
TreeFamiTF332773.

Family and domain databases

InterProiIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PfamiPF00008. EGF. 1 hit.
[Graphical view]
SMARTiSM00181. EGF. 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.

Q06186-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MKLLPSVMLK LFLAAVLSAL VTGESLERLR RGLAAATSNP DPPTGSTNQL
60 70 80 90 100
LPTGGDRAQG VQDLEGTDLN LFKVAFSSKP QGLATPSKER NGKKKKKGKG
110 120 130 140 150
LGKKRDPCLR KYKDYCIHGE CRYLQEFRTP SCKCLPGYHG HRCHGLTLPV
160 170 180 190 200
ENPLYTYDHT TVLAVVAVVL SSVCLLVIVG LLMFRYHRRG GYDLESEEKV

KLGVASSH
Length:208
Mass (Da):22,808
Last modified:February 1, 1995 - v1
Checksum:i7086934E23D25F8E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36027
, L36024, L36025, L36026 Genomic DNA. Translation: AAC42069.1.
L07264 mRNA. Translation: AAA37542.1.
U39192
, U39189, U39190, U39191 Genomic DNA. Translation: AAC52617.1.
CCDSiCCDS29153.1.
PIRiJC1410.
RefSeqiNP_034545.1. NM_010415.2.
UniGeneiMm.289681.

Genome annotation databases

EnsembliENSMUST00000025363; ENSMUSP00000025363; ENSMUSG00000024486.
GeneIDi15200.
KEGGimmu:15200.
UCSCiuc008enl.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36027
, L36024, L36025, L36026 Genomic DNA. Translation: AAC42069.1.
L07264 mRNA. Translation: AAA37542.1.
U39192
, U39189, U39190, U39191 Genomic DNA. Translation: AAC52617.1.
CCDSiCCDS29153.1.
PIRiJC1410.
RefSeqiNP_034545.1. NM_010415.2.
UniGeneiMm.289681.

3D structure databases

ProteinModelPortaliQ06186.
SMRiQ06186. Positions 107-147.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025363.

PTM databases

PhosphoSiteiQ06186.

Proteomic databases

MaxQBiQ06186.
PRIDEiQ06186.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025363; ENSMUSP00000025363; ENSMUSG00000024486.
GeneIDi15200.
KEGGimmu:15200.
UCSCiuc008enl.2. mouse.

Organism-specific databases

CTDi1839.
MGIiMGI:96070. Hbegf.

Phylogenomic databases

eggNOGiNOG45526.
HOGENOMiHOG000026782.
HOVERGENiHBG053952.
InParanoidiQ06186.
KOiK08523.
OMAiYSYDHTT.
OrthoDBiEOG7VQJGP.
PhylomeDBiQ06186.
TreeFamiTF332773.

Enzyme and pathway databases

ReactomeiREACT_188191. Signaling by ERBB2.
REACT_188528. GRB2 events in ERBB2 signaling.
REACT_188574. SHC1 events in ERBB2 signaling.
REACT_188579. Signaling by ERBB4.
REACT_188580. SHC1 events in ERBB4 signaling.
REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
REACT_198350. EGFR Transactivation by Gastrin.
REACT_198574. Nuclear signaling by ERBB4.
REACT_203296. PI3K events in ERBB4 signaling.
REACT_215348. PI3K events in ERBB2 signaling.
REACT_226341. PIP3 activates AKT signaling.

Miscellaneous databases

NextBioi287735.
PMAP-CutDBQ06186.
PROiQ06186.
SOURCEiSearch...

Gene expression databases

BgeeiQ06186.
CleanExiMM_HBEGF.
ExpressionAtlasiQ06186. baseline and differential.
GenevestigatoriQ06186.

Family and domain databases

InterProiIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PfamiPF00008. EGF. 1 hit.
[Graphical view]
SMARTiSM00181. EGF. 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: Macrophage.
  2. "Characterization of the gene encoding murine heparin-binding epidermal growth factor-like growth factor."
    Harding P.A., Brigstock D.R., Shen L., Crissman-Combs M.A., Besner G.E.
    Gene 169:291-292(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129/SvJ.

Entry informationi

Entry nameiHBEGF_MOUSE
AccessioniPrimary (citable) accession number: Q06186
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: February 4, 2015
This is version 123 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.