Q06186 (HBEGF_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proheparin-binding EGF-like growth factor

Cleaved into the following chain:

1. Heparin-binding EGF-like growth factor
   Short name=HB-EGF
   Short name=HBEGF

Gene names

Name:	Hbegf
Synonyms:	Dtr, Hegfl

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	208 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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.
Subunit structure	Interacts with FBLN1 By similarity. Interacts with EGFR and ERBB4.
Subcellular location	Heparin-binding EGF-like growth factor: Secreted › extracellular space. Note: Mature HB-EGF is released into the extracellular space and probably binds to a receptor. Proheparin-binding EGF-like growth factor: Cell membrane; Single-pass type I membrane protein.
Tissue specificity	Most abundant in kidney, skeletal muscle, lung, spleen, brain and heart.
Post-translational modification	O-glycosylated By similarity.
Sequence similarities	Contains 1 EGF-like domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Domain	EGF-like domain Signal Transmembrane Transmembrane helix
Ligand	Heparin-binding
Molecular function	Growth factor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Non-traceable author statement PubMed 15289334. Source: UniProtKB blastocyst growth Traceable author statement PubMed 10101133. Source: UniProtKB epidermal growth factor receptor signaling pathway Inferred from direct assay PubMed 12621152. Source: MGI negative regulation of elastin biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of cell growth Inferred from electronic annotation. Source: Compara positive regulation of keratinocyte migration Inferred from mutant phenotype PubMed 15923649. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara positive regulation of smooth muscle cell proliferation Inferred from direct assay PubMed 1840698. Source: UniProtKB positive regulation of wound healing Inferred from electronic annotation. Source: Compara regulation of heart contraction Inferred from mutant phenotype PubMed 12621152. Source: MGI wound healing, spreading of epidermal cells Inferred from mutant phenotype PubMed 15923649. Source: UniProtKB
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara extracellular space Inferred from direct assay PubMed 9857183. Source: BHF-UCL integral to plasma membrane Inferred from direct assay PubMed 9857183. Source: BHF-UCL
Molecular_function	epidermal growth factor receptor binding Inferred from direct assay PubMed 1840698. Source: UniProtKB eukaryotic cell surface binding Inferred from electronic annotation. Source: Compara growth factor activity Inferred from direct assay PubMed 1840698. Source: UniProtKB heparin binding Inferred from direct assay PubMed 1840698. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 208	185	Proheparin-binding EGF-like growth factor		PRO_0000302804
	Propeptide	24 – 62	39	By similarity		PRO_0000007614
	Chain	63 – 148	86	Heparin-binding EGF-like growth factor		PRO_0000007615
	Propeptide	149 – 208	60	C-terminal Potential		PRO_0000007616
Regions
	Topological domain	24 – 160	137	Extracellular Potential
	Transmembrane	161 – 184	24	Helical; Potential
	Topological domain	185 – 208	24	Cytoplasmic Potential
	Domain	104 – 144	41	EGF-like
Amino acid modifications
	Glycosylation	85	1	O-linked (GalNAc...) By similarity
	Disulfide bond	108 ↔ 121		By similarity
	Disulfide bond	116 ↔ 132		By similarity
	Disulfide bond	134 ↔ 143		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q06186 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 7086934E23D25F8E	FASTA	208	22,808
	10 20 30 40 50 60 MKLLPSVMLK LFLAAVLSAL VTGESLERLR RGLAAATSNP DPPTGSTNQL LPTGGDRAQG 70 80 90 100 110 120 VQDLEGTDLN LFKVAFSSKP QGLATPSKER NGKKKKKGKG LGKKRDPCLR KYKDYCIHGE 130 140 150 160 170 180 CRYLQEFRTP SCKCLPGYHG HRCHGLTLPV ENPLYTYDHT TVLAVVAVVL SSVCLLVIVG 190 200 LLMFRYHRRG GYDLESEEKV KLGVASSH

References

[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L36027 , L36024, L36025, L36026 Genomic DNA. Translation: AAC42069.1. L07264 mRNA. Translation: AAA37542.1. U39192 , U39189, U39190, U39191 Genomic DNA. Translation: AAC52617.1.
IPI	IPI00111772.
PIR	JC1410.
RefSeq	NP_034545.1. NM_010415.2.
UniGene	Mm.289681.
3D structure databases
ProteinModelPortal	Q06186.
SMR	Q06186. Positions 107-147.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000025363.
PTM databases
PhosphoSite	Q06186.
Proteomic databases
PRIDE	Q06186.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000025363; ENSMUSP00000025363; ENSMUSG00000024486.
GeneID	15200.
KEGG	mmu:15200.
Organism-specific databases
CTD	1839.
MGI	MGI:96070. Hbegf.
Phylogenomic databases
eggNOG	NOG45526.
HOGENOM	HOG000026782.
HOVERGEN	HBG053952.
InParanoid	Q06186.
KO	K08523.
OMA	PTESTDQ.
OrthoDB	EOG476K1S.
Enzyme and pathway databases
Reactome	REACT_115202. Signal Transduction.
Gene expression databases
ArrayExpress	Q06186.
Bgee	Q06186.
CleanEx	MM_HBEGF.
Genevestigator	Q06186.
GermOnline	ENSMUSG00000024486. Mus musculus.
Family and domain databases
InterPro	IPR000742. EG-like_dom. IPR013032. EGF-like_CS. IPR015497. EGF_rcpt_ligand. [Graphical view]
PANTHER	PTHR10740. PTHR10740. 1 hit.
Pfam	PF00008. EGF. 1 hit. [Graphical view]
SMART	SM00181. EGF. 1 hit. [Graphical view]
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	287735.
PMAP-CutDB	Q06186.
SOURCE	Search...

Entry information

Entry name

HBEGF_MOUSE

Accession

Primary (citable) accession number: Q06186

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	April 3, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program