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This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
ERBB3 (Erb-B2 Receptor Tyrosine Kinase 3) is a Protein Coding gene. Diseases associated with ERBB3 include Lethal Congenital Contracture Syndrome 2 and Erythroleukemia, Familial. Among its related pathways are RET signaling and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and transferase activity, transferring phosphorus-containing groups. An important paralog of this gene is ERBB4.
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB family. Four members of the ErbB family have been identified; EGFR (ErbB1, HER1), ErbB2 (HER2), ErbB3 (HER3) and ErbB4 (HER4). EGFR signaling drives many cellular responses.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | NOT protein tyrosine kinase activity | IEA,IDA | 7556068 |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IBA | 21873635 |
GO:0004888 | transmembrane signaling receptor activity | ISS | 7514177 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | IEA | -- |
GO:0005615 | extracellular space | IDA | 11389077 |
GO:0005886 | plasma membrane | TAS | 17701904 |
GO:0005887 | integral component of plasma membrane | TAS,IBA | 21873635 |
GO:0009925 | basal plasma membrane | IBA | 21873635 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
3 | GAB1 signalosome |
.89
|
|
4 | Signaling by ERBB2 | ||
5 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0003197 | endocardial cushion development | IEA | -- |
GO:0006468 | protein phosphorylation | IEA | -- |
GO:0007162 | negative regulation of cell adhesion | IDA | 7556068 |
GO:0007165 | signal transduction | IDA | 10572067 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Gefitinib | Approved, Investigational | Pharma | Biomarker, inhibitor | EGFR Inhibitors, Kinase Inhibitors, Epidermal growth factor receptor (EGFR) inhibitors | 409 | |
Trastuzumab | Approved, Investigational | Pharma | HER2 antagonist, HER2 Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors | 1006 | ||
Tyrosine | Approved, Investigational | Nutra | 1044 | |||
Tucatinib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
Carboplatin | Approved | Pharma | Antitumor agent that forms platinum-DNA adducts., Platinum | 2588 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
||
CP 724714 |
|
383432-38-0 |
|
|
Compound | Action | Cas Number |
---|---|---|
AG 490 | EGFR-kinase inhibitor. Also JAK2, JAK3 inhibitor | 133550-30-8 |
CGP 52411 | EGFR inhibitor. Also inhibits Abeta42 fibril formation | 145915-58-8 |
CP 724714 | Potent and selective ErbB2 inhibitor | 383432-38-0 |
Genistein | EGFR kinase inhibitor. Also estrogen and PPARgamma ligand | 446-72-0 |
Compound | Action | Cas Number |
---|---|---|
AZD8931 (Sapitinib) | ErbB inhibitor | 848942-61-0 |
Poziotinib | irreversible pan-HER inhibitor | 1092364-38-9 |
Varlitinib (ARRY334543) | ErbB inhibitor | 845272-21-1 |
ExUns: | 1a | · | 1b | · | 1c | · | 1d | ^ | 2 | ^ | 3 | ^ | 4a | · | 4b | ^ | 5 | ^ | 6 | ^ | 7a | · | 7b | ^ | 8 | ^ | 9 | ^ | 10 | ^ | 11 | ^ | 12 | ^ | 13a | · | 13b | ^ | 14a | · | 14b | ^ | 15 | ^ | 16a | · | 16b | · | 16c | ^ | 17 | ^ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | ||||||||||||||||||||||||||||||||||||||||||||||||||
SP3: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP4: | - | - | - | - | - | - | - | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||||||||||||
SP5: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP6: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP7: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP8: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP9: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP10: | - | |||||||||||||||||||||||||||||||||||||||||||||||||||
SP11: | ||||||||||||||||||||||||||||||||||||||||||||||||||||
SP12: |
ExUns: | 18 | ^ | 19a | · | 19b | · | 19c | ^ | 20 | ^ | 21 | ^ | 22a | · | 22b | ^ | 23a | · | 23b | ^ | 24a | · | 24b | ^ | 25 | ^ | 26 | ^ | 27a | · | 27b | ^ | 28 | ^ | 29 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | - | - | ||||||||||||||||||||||||||||||||
SP2: | - | - | - | - | - | - | - | ||||||||||||||||||||||||||||
SP3: | - | - | |||||||||||||||||||||||||||||||||
SP4: | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | ||||||||||||||||||||
SP5: | |||||||||||||||||||||||||||||||||||
SP6: | |||||||||||||||||||||||||||||||||||
SP7: | |||||||||||||||||||||||||||||||||||
SP8: | |||||||||||||||||||||||||||||||||||
SP9: | - | ||||||||||||||||||||||||||||||||||
SP10: | |||||||||||||||||||||||||||||||||||
SP11: | |||||||||||||||||||||||||||||||||||
SP12: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | ERBB3 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | -- 31 |
|
OneToMany | |
-- 31 |
|
OneToMany | |||
Dog (Canis familiaris) |
Mammalia | ERBB3 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | ERBB3 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Erbb3 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | ERBB3 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Erbb3 30 17 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | ERBB3 30 |
|
||
Lizard (Anolis carolinensis) |
Reptilia | ERBB3 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | erbb3 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | erbb3a 31 |
|
OneToMany | |
erbb3b 31 |
|
OneToMany | |||
Fruit Fly (Drosophila melanogaster) |
Insecta | Egfr 32 |
|
|
|
Worm (Caenorhabditis elegans) |
Secernentea | let-23 32 |
|
|