Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Proheparin-binding EGF-like growth factor

Gene

HBEGF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei141Plays a critical role in diphtheria toxin binding and toxin sensitivityBy similarity1

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: ProtInc
  • growth factor activity Source: UniProtKB
  • heparin binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • protein tyrosine kinase activity Source: Reactome
  • Ras guanyl-nucleotide exchange factor activity Source: Reactome

GO - Biological processi

  • cell chemotaxis Source: UniProtKB
  • epidermal growth factor receptor signaling pathway Source: BHF-UCL
  • ERBB2 signaling pathway Source: Reactome
  • MAPK cascade Source: Reactome
  • muscle organ development Source: ProtInc
  • negative regulation of elastin biosynthetic process Source: Ensembl
  • phosphatidylinositol-mediated signaling Source: Reactome
  • positive regulation of cell growth Source: Ensembl
  • positive regulation of cell migration Source: BHF-UCL
  • positive regulation of cell proliferation Source: GO_Central
  • positive regulation of keratinocyte migration Source: Ensembl
  • positive regulation of protein kinase B signaling Source: BHF-UCL
  • positive regulation of smooth muscle cell proliferation Source: Ensembl
  • positive regulation of wound healing Source: BHF-UCL
  • regulation of cell motility Source: Reactome
  • regulation of heart contraction Source: Ensembl
  • regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
  • signal transduction Source: ProtInc
  • wound healing, spreading of epidermal cells Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Receptor

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113070-MONOMER.
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-2179392. EGFR Transactivation by Gastrin.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5336415. Uptake and function of diphtheria toxin.
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.
R-HSA-8857538. PTK6 promotes HIF1A stabilization.
R-HSA-8863795. Downregulation of ERBB2 signaling.
SignaLinkiQ99075.
SIGNORiQ99075.

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
Alternative name(s):
Diphtheria toxin receptor
Short name:
DT-R
Gene namesi
Name:HBEGF
Synonyms:DTR, DTS, HEGFL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:3059. HBEGF.

Subcellular locationi

Heparin-binding EGF-like growth factor :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 160ExtracellularSequence analysisAdd BLAST141
Transmembranei161 – 184HelicalSequence analysisAdd BLAST24
Topological domaini185 – 208CytoplasmicSequence analysisAdd BLAST24

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • clathrin-coated endocytic vesicle membrane Source: Reactome
  • endocytic vesicle membrane Source: Reactome
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi1839.
OpenTargetsiENSG00000113070.
PharmGKBiPA27513.

Chemistry databases

ChEMBLiCHEMBL3286070.

Polymorphism and mutation databases

BioMutaiHBEGF.
DMDMi544477.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000030280320 – 208Proheparin-binding EGF-like growth factorAdd BLAST189
PropeptideiPRO_000000761120 – 62Or 72, or 73, or 76, or 811 PublicationAdd BLAST43
ChainiPRO_000000761263 – 148Heparin-binding EGF-like growth factorAdd BLAST86
PropeptideiPRO_0000007613149 – 208C-terminalSequence analysisAdd BLAST60

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi37O-linked (GalNAc...)1 Publication1
Glycosylationi38O-linked (GalNAc...)1 Publication1
Glycosylationi44O-linked (GalNAc...)2 Publications1
Glycosylationi47O-linked (GalNAc...)1 Publication1
Glycosylationi75O-linked (GalNAc...)1 Publication1
Glycosylationi85O-linked (GalNAc...)1 Publication1
Disulfide bondi108 ↔ 121PROSITE-ProRule annotation
Disulfide bondi116 ↔ 132PROSITE-ProRule annotation
Disulfide bondi134 ↔ 143PROSITE-ProRule annotation

Post-translational modificationi

Several N-termini have been identified by direct sequencing. The forms with N-termini 63, 73 and 74 have been tested and found to be biologically active.
O-glycosylated with core 1 or possibly core 8 glycans. Thr-47 is a minor glycosylation site compared to Thr-44.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ99075.
PeptideAtlasiQ99075.
PRIDEiQ99075.

PTM databases

iPTMnetiQ99075.
PhosphoSitePlusiQ99075.
UniCarbKBiQ99075.

Miscellaneous databases

PMAP-CutDBQ99075.

Expressioni

Gene expression databases

BgeeiENSG00000113070.
CleanExiHS_HBEGF.
GenevisibleiQ99075. HS.

Organism-specific databases

HPAiHPA053243.

Interactioni

Subunit structurei

Interacts with FBLN1 (By similarity). Interacts with EGFR and ERBB4.By similarity2 Publications

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: ProtInc
  • growth factor activity Source: UniProtKB

Protein-protein interaction databases

BioGridi108172. 9 interactors.
DIPiDIP-114N.
IntActiQ99075. 1 interactor.
MINTiMINT-1511911.
STRINGi9606.ENSP00000230990.

Chemistry databases

BindingDBiQ99075.

Structurei

Secondary structure

1208
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni108 – 114Combined sources7
Beta strandi117 – 121Combined sources5
Turni125 – 128Combined sources4
Beta strandi132 – 134Combined sources3
Beta strandi138 – 140Combined sources3
Beta strandi188 – 195Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XDTX-ray2.65R73-147[»]
2M8SNMR-B185-208[»]
ProteinModelPortaliQ99075.
SMRiQ99075.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99075.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini104 – 144EGF-likePROSITE-ProRule annotationAdd BLAST41

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.
InParanoidiQ99075.
KOiK08523.
OMAiYSYDHTT.
OrthoDBiEOG091G0RK4.
PhylomeDBiQ99075.
TreeFamiTF332773.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PfamiPF00008. 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.

Q99075-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKLLPSVVLK LFLAAVLSAL VTGESLERLR RGLAAGTSNP DPPTVSTDQL
60 70 80 90 100
LPLGGGRDRK VRDLQEADLD LLRVTLSSKP QALATPNKEE HGKRKKKGKG
110 120 130 140 150
LGKKRDPCLR KYKDFCIHGE CKYVKELRAP SCICHPGYHG ERCHGLSLPV
160 170 180 190 200
ENRLYTYDHT TILAVVAVVL SSVCLLVIVG LLMFRYHRRG GYDVENEEKV

KLGMTNSH
Length:208
Mass (Da):23,067
Last modified:June 1, 1994 - v1
Checksum:i2C43C9D1D8291B51
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60278 mRNA. Translation: AAA35956.1.
AY164533 Genomic DNA. Translation: AAN46738.1.
AK313202 mRNA. Translation: BAG36018.1.
AC004634 Genomic DNA. Translation: AAC15470.1.
CH471062 Genomic DNA. Translation: EAW62069.1.
BC033097 mRNA. Translation: AAH33097.1.
CCDSiCCDS4223.1.
PIRiA38432.
RefSeqiNP_001936.1. NM_001945.2.
UniGeneiHs.592942.
Hs.799.

Genome annotation databases

EnsembliENST00000230990; ENSP00000230990; ENSG00000113070.
GeneIDi1839.
KEGGihsa:1839.
UCSCiuc003lfi.4. human.

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M60278 mRNA. Translation: AAA35956.1.
AY164533 Genomic DNA. Translation: AAN46738.1.
AK313202 mRNA. Translation: BAG36018.1.
AC004634 Genomic DNA. Translation: AAC15470.1.
CH471062 Genomic DNA. Translation: EAW62069.1.
BC033097 mRNA. Translation: AAH33097.1.
CCDSiCCDS4223.1.
PIRiA38432.
RefSeqiNP_001936.1. NM_001945.2.
UniGeneiHs.592942.
Hs.799.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XDTX-ray2.65R73-147[»]
2M8SNMR-B185-208[»]
ProteinModelPortaliQ99075.
SMRiQ99075.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108172. 9 interactors.
DIPiDIP-114N.
IntActiQ99075. 1 interactor.
MINTiMINT-1511911.
STRINGi9606.ENSP00000230990.

Chemistry databases

BindingDBiQ99075.
ChEMBLiCHEMBL3286070.

PTM databases

iPTMnetiQ99075.
PhosphoSitePlusiQ99075.
UniCarbKBiQ99075.

Polymorphism and mutation databases

BioMutaiHBEGF.
DMDMi544477.

Proteomic databases

PaxDbiQ99075.
PeptideAtlasiQ99075.
PRIDEiQ99075.

Protocols and materials databases

DNASUi1839.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000230990; ENSP00000230990; ENSG00000113070.
GeneIDi1839.
KEGGihsa:1839.
UCSCiuc003lfi.4. human.

Organism-specific databases

CTDi1839.
DisGeNETi1839.
GeneCardsiHBEGF.
HGNCiHGNC:3059. HBEGF.
HPAiHPA053243.
MIMi126150. gene.
neXtProtiNX_Q99075.
OpenTargetsiENSG00000113070.
PharmGKBiPA27513.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IMHM. Eukaryota.
ENOG41120D3. LUCA.
GeneTreeiENSGT00530000063708.
HOGENOMiHOG000026782.
HOVERGENiHBG053952.
InParanoidiQ99075.
KOiK08523.
OMAiYSYDHTT.
OrthoDBiEOG091G0RK4.
PhylomeDBiQ99075.
TreeFamiTF332773.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113070-MONOMER.
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-2179392. EGFR Transactivation by Gastrin.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-5336415. Uptake and function of diphtheria toxin.
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.
R-HSA-8857538. PTK6 promotes HIF1A stabilization.
R-HSA-8863795. Downregulation of ERBB2 signaling.
SignaLinkiQ99075.
SIGNORiQ99075.

Miscellaneous databases

EvolutionaryTraceiQ99075.
GeneWikiiHeparin-binding_EGF-like_growth_factor.
GenomeRNAii1839.
PMAP-CutDBQ99075.
PROiQ99075.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113070.
CleanExiHS_HBEGF.
GenevisibleiQ99075. HS.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR015497. EGF_rcpt_ligand.
[Graphical view]
PANTHERiPTHR10740. PTHR10740. 1 hit.
PfamiPF00008. EGF. 1 hit.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHBEGF_HUMAN
AccessioniPrimary (citable) accession number: Q99075
Secondary accession number(s): B2R821
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 30, 2016
This is version 163 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, Direct protein sequencing, Reference proteome

Documents

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