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Protein

Proheparin-binding EGF-like growth factor

Gene

HBEGF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionGrowth factor, Heparin-binding, Receptor

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000113070.7
HGNCiHGNC:3059 HBEGF
MIMi126150 gene
neXtProtiNX_Q99075

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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...) threonine1 Publication1
Glycosylationi38O-linked (GalNAc...) serine1 Publication1
Glycosylationi44O-linked (GalNAc...) threonine2 Publications1
Glycosylationi47O-linked (GalNAc...) threonine1 Publication1
Glycosylationi75O-linked (GalNAc...) threonine1 Publication1
Glycosylationi85O-linked (GalNAc...) threonine1 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
ProteomicsDBi78230

PTM databases

GlyConnecti809
iPTMnetiQ99075
PhosphoSitePlusiQ99075
UniCarbKBiQ99075

Miscellaneous databases

PMAP-CutDBiQ99075

Expressioni

Gene expression databases

BgeeiENSG00000113070 Expressed in 193 organ(s), highest expression level in synovial joint
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

Protein-protein interaction databases

BioGridi108172, 9 interactors
DIPiDIP-114N
IntActiQ99075, 1 interactor
MINTiQ99075
STRINGi9606.ENSP00000230990

Chemistry databases

BindingDBiQ99075

Structurei

Secondary structure

1208
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ99075
SMRiQ99075
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99075

Family & Domainsi

Domains and Repeats

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

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR015497 EGF_rcpt_ligand
PANTHERiPTHR10740 PTHR10740, 1 hit
PfamiView protein in Pfam
PF00008 EGF, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 1 hit
PS01186 EGF_2, 1 hit
PS50026 EGF_3, 1 hit

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

Similar proteinsi

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
MINTiQ99075
STRINGi9606.ENSP00000230990

Chemistry databases

BindingDBiQ99075
ChEMBLiCHEMBL3286070

PTM databases

GlyConnecti809
iPTMnetiQ99075
PhosphoSitePlusiQ99075
UniCarbKBiQ99075

Polymorphism and mutation databases

BioMutaiHBEGF
DMDMi544477

Proteomic databases

PaxDbiQ99075
PeptideAtlasiQ99075
PRIDEiQ99075
ProteomicsDBi78230

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
EuPathDBiHostDB:ENSG00000113070.7
GeneCardsiHBEGF
HGNCiHGNC:3059 HBEGF
HPAiHPA053243
MIMi126150 gene
neXtProtiNX_Q99075
OpenTargetsiENSG00000113070
PharmGKBiPA27513
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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-CutDBiQ99075
PROiPR:Q99075
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113070 Expressed in 193 organ(s), highest expression level in synovial joint
CleanExiHS_HBEGF
GenevisibleiQ99075 HS

Family and domain databases

InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR015497 EGF_rcpt_ligand
PANTHERiPTHR10740 PTHR10740, 1 hit
PfamiView protein in Pfam
PF00008 EGF, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 1 hit
PS01186 EGF_2, 1 hit
PS50026 EGF_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHBEGF_HUMAN
AccessioniPrimary (citable) accession number: Q99075
Secondary accession number(s): B2R821
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: September 12, 2018
This is version 174 of the entry and version 1 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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