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Q06186

- HBEGF_MOUSE

UniProt

Q06186 - HBEGF_MOUSE

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Protein
Proheparin-binding EGF-like growth factor
Gene
Hbegf, Dtr, Hegfl
Organism
Mus musculus (Mouse)
Status
Reviewed - 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
Complete GO annotation...

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 keratinocyte migration Source: UniProtKB
  8. positive regulation of protein kinase B signaling Source: Ensembl
  9. positive regulation of smooth muscle cell proliferation Source: UniProtKB
  10. positive regulation of wound healing Source: Ensembl
  11. regulation of heart contraction Source: MGI
  12. 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 – 160137Extracellular Reviewed prediction
Add
BLAST
Transmembranei161 – 18424Helical; Reviewed prediction
Add
BLAST
Topological domaini185 – 20824Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. cell surface Source: Ensembl
  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 – 2323 Reviewed prediction
Add
BLAST
Chaini24 – 208185Proheparin-binding EGF-like growth factor
PRO_0000302804Add
BLAST
Propeptidei24 – 6239 By similarity
PRO_0000007614Add
BLAST
Chaini63 – 14886Heparin-binding EGF-like growth factor
PRO_0000007615Add
BLAST
Propeptidei149 – 20860C-terminal Reviewed prediction
PRO_0000007616Add
BLAST

Amino acid modifications

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

Post-translational modificationi

O-glycosylated By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

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

ArrayExpressiQ06186.
BgeeiQ06186.
CleanExiMM_HBEGF.
GenevestigatoriQ06186.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025363.

Structurei

3D structure databases

ProteinModelPortaliQ06186.
SMRiQ06186. Positions 107-147.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini104 – 14441EGF-like
Add
BLAST

Sequence similaritiesi

Contains 1 EGF-like domain.

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

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MKLLPSVMLK LFLAAVLSAL VTGESLERLR RGLAAATSNP DPPTGSTNQL    50
LPTGGDRAQG VQDLEGTDLN LFKVAFSSKP QGLATPSKER NGKKKKKGKG 100
LGKKRDPCLR KYKDYCIHGE CRYLQEFRTP SCKCLPGYHG HRCHGLTLPV 150
ENPLYTYDHT TVLAVVAVVL SSVCLLVIVG LLMFRYHRRG GYDLESEEKV 200
KLGVASSH 208
Length:208
Mass (Da):22,808
Last modified:February 1, 1995 - v1
Checksum:i7086934E23D25F8E
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS29153.1.
PIRi JC1410.
RefSeqi NP_034545.1. NM_010415.2.
UniGenei Mm.289681.

3D structure databases

ProteinModelPortali Q06186.
SMRi Q06186. Positions 107-147.
ModBasei Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000025363.

PTM databases

PhosphoSitei Q06186.

Proteomic databases

PRIDEi Q06186.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000025363 ; ENSMUSP00000025363 ; ENSMUSG00000024486 .
GeneIDi 15200.
KEGGi mmu:15200.
UCSCi uc008enl.2. mouse.

Organism-specific databases

CTDi 1839.
MGIi MGI:96070. Hbegf.

Phylogenomic databases

eggNOGi NOG45526.
HOGENOMi HOG000026782.
HOVERGENi HBG053952.
InParanoidi Q06186.
KOi K08523.
OMAi YSYDHTT.
OrthoDBi EOG7VQJGP.
PhylomeDBi Q06186.
TreeFami TF332773.

Enzyme and pathway databases

Reactomei REACT_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

NextBioi 287735.
PMAP-CutDB Q06186.
PROi Q06186.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q06186.
Bgeei Q06186.
CleanExi MM_HBEGF.
Genevestigatori Q06186.

Family and domain databases

InterProi IPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR015497. EGF_rcpt_ligand.
[Graphical view ]
PANTHERi PTHR10740. PTHR10740. 1 hit.
Pfami PF00008. EGF. 1 hit.
[Graphical view ]
SMARTi SM00181. EGF. 1 hit.
[Graphical view ]
PROSITEi PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
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. 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

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