ID:HBEGF_HUMAN DESCRIPTION: RecName: Full=Proheparin-binding EGF-like growth factor; Contains: RecName: Full=Heparin-binding EGF-like growth factor; Short=HB-EGF; Short=HBEGF; AltName: Full=Diphtheria toxin receptor; Short=DT-R; Flags: Precursor; 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: 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. SUBCELLULAR LOCATION: Proheparin-binding EGF-like growth factor: Cell membrane; Single-pass type I membrane protein. PTM: 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. PTM: O-glycosylated with core 1 or possibly core 8 glycans. Thr-47 is a minor glycosylation site compared to Thr-44. SIMILARITY: Contains 1 EGF-like domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/dtr/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q99075
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart)
Reactome (by CSHL, EBI, and GO)
Protein Q99075 (Reactome details) participates in the following event(s):
R-HSA-2179402 Active MMP3 can cleave pro-HBEGF to form active HBEGF R-HSA-5336417 DT A:B binds HBEGF and CD9 on the target cell surface R-HSA-8857549 HBEGF-bound EGFR forms a heterodimer with GPNMB R-HSA-2179415 GRB2:SOS1 binds to HBEGF:p-Y-EGFR R-HSA-8857555 EGFR phosphorylates GPNMB R-HSA-8857565 Phosphorylated GPNMB recruits PTK6 and LRRK2 in the presence of LINC01139 R-HSA-1236398 ERBB4 binds NRGs or EGF-like ligands R-HSA-8857577 LINC01139 facilitates PTK6 autophosphorylation R-HSA-2179407 SOS1-mediated nucleotide exchange of RAS (HB-EFG-initiated) R-HSA-8857583 LINC01139 promotes phosphorylation of HIF1A by PTK6 and LRRK2 R-HSA-1963589 ERBB2 forms heterodimers with ligand-activated ERBB receptors: EGFR, ERBB3 and ERBB4 R-NUL-1251988 Cleavage of P-ERBB4jmA isoforms by Adam17 R-HSA-1250220 Homodimerization of ERBB4 R-HSA-1977958 ERBB4 forms heterodimers with ERBB3 R-HSA-1977959 ERBB4 forms heterodimers with EGFR R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange R-HSA-1250346 Binding of PI3K to p-ERBB2:p-ERBB4 CYT-1 heterodimers R-HSA-1250357 SHC1 binds P-ERBB4 isoform dimers R-HSA-1250315 Trans-autophosphorylation of ERBB4 homodimers R-HSA-1251992 Cleavage of P-ERBB4jmA isoforms by ADAM17 R-HSA-1250353 Binding of p85 subunit of PI3K (PIK3R1) to p-ERBB4cyt1 homodimers R-HSA-1963582 Trans-autophosphorylation of ERBB2 heterodimers R-HSA-1963586 SRC family kinases phosphorylate ERBB2 R-HSA-1963581 Trans-autophosphorylation of p-Y877-ERBB2 heterodimers R-HSA-1306969 GRB2:SOS1 complex binds phosphorylated ERBB4:ERBB2 heterodimers R-HSA-1250380 Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers R-HSA-1250348 Phosphorylation of SHC1 by ERBB4 homodimers R-HSA-1250372 Recruitment of PI3K subunit p110 (PIK3CA) to PI3K subunit p85 (PIK3R1) bound to p-ERBB4cyt1 homodimers R-HSA-1306979 PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB4 CYT1 R-HSA-1963563 MATK (CSK homologous kinase) binds phosphorylated ERBB2 R-HSA-1963578 SHC1 binds phosphorylated ERBB2 heterodimers R-HSA-6785636 Phosphorylated ERBB2 heterodimers bind MEMO1 R-HSA-8847995 Activated ERBB2 binds PTK6 (BRK) R-HSA-8863804 PTPN12 dephosphorylates ERBB2 on tyrosine Y1248 R-HSA-8848005 ERBB2 promotes PTK6 autophosphorylation R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3 R-HSA-1306972 RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers R-HSA-1250195 SHC1 phosphorylation by ERBB2 heterodimers R-HSA-1250486 Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 heterodimers R-HSA-6785648 MEMO1 binds RHOA:GTP:DIAPH1 R-HSA-1250383 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4 R-HSA-1250370 Conversion of PIP2 into PIP3 by PI3K bound to p-ERBB4cyt1 homodimers R-HSA-1250463 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-SHC1:Phosphorylated ERBB2 heterodimers R-HSA-2179392 EGFR Transactivation by Gastrin R-HSA-5336415 Uptake and function of diphtheria toxin R-HSA-8857538 PTK6 promotes HIF1A stabilization R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-5339562 Uptake and actions of bacterial toxins R-HSA-8848021 Signaling by PTK6 R-HSA-1236394 Signaling by ERBB4 R-HSA-416476 G alpha (q) signalling events R-HSA-5663205 Infectious disease R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-388396 GPCR downstream signalling R-HSA-1643685 Disease R-HSA-162582 Signal Transduction R-HSA-1227986 Signaling by ERBB2 R-HSA-372790 Signaling by GPCR R-HSA-5673001 RAF/MAP kinase cascade R-HSA-1963642 PI3K events in ERBB2 signaling R-HSA-1250347 SHC1 events in ERBB4 signaling R-HSA-1251985 Nuclear signaling by ERBB4 R-HSA-1250342 PI3K events in ERBB4 signaling R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-1963640 GRB2 events in ERBB2 signaling R-HSA-5683057 MAPK family signaling cascades R-HSA-8863795 Downregulation of ERBB2 signaling R-HSA-1250196 SHC1 events in ERBB2 signaling R-HSA-6785631 ERBB2 Regulates Cell Motility R-HSA-8847993 ERBB2 Activates PTK6 Signaling R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer R-HSA-1257604 PIP3 activates AKT signaling R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-2219528 PI3K/AKT Signaling in Cancer R-HSA-9006925 Intracellular signaling by second messengers R-HSA-199418 Negative regulation of the PI3K/AKT network R-HSA-5663202 Diseases of signal transduction
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
