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ERBB4

Summary: This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008].

Name	OMIM ID	Ensembl ID	HGNC ID	PHARMGKB ID	Map Location
erb-b2 receptor tyrosine kinase 4	MIM:600543	Ensembl:ENSG00000178568	HGNC:HGNC:3432	PA27847	2q34

Gene Categories:

TYROSINE KINASE DRUGGABLE GENOME KINASE CLINICALLY ACTIONABLE

GO terms in ERBB4

Term Type	Evidence Type	GO Term ID	GO Des.
BP	TAS	GO:0000165	MAPK cascade
BP	ISS	GO:0001755	neural crest cell migration
BP	TAS	GO:0001934	positive regulation of protein phosphorylation
BP	IEA	GO:0006351	transcription, DNA-templated
BP	IDA	GO:0007165	signal transduction
BP	IDA	GO:0007169	transmembrane receptor protein tyrosine kinase signaling pathway
BP	IBA	GO:0007275	multicellular organism development
BP	ISS	GO:0007399	nervous system development
BP	ISS	GO:0007507	heart development
BP	IMP	GO:0007595	lactation
BP	TAS	GO:0008283	cell proliferation
BP	IMP	GO:0008284	positive regulation of cell proliferation
BP	IMP	GO:0008285	negative regulation of cell proliferation
BP	ISS	GO:0009880	embryonic pattern specification
BP	IBA	GO:0009968	negative regulation of signal transduction
BP	IEA	GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
BP	IDA	GO:0016477	cell migration
BP	IDA	GO:0018108	peptidyl-tyrosine phosphorylation
BP	ISS	GO:0021551	central nervous system morphogenesis
BP	ISS	GO:0021889	olfactory bulb interneuron differentiation
BP	IBA	GO:0030154	cell differentiation
BP	ISS	GO:0030334	regulation of cell migration
BP	IBA	GO:0033674	positive regulation of kinase activity
BP	IEA	GO:0038083	peptidyl-tyrosine autophosphorylation
BP	TAS	GO:0038128	ERBB2 signaling pathway
BP	IMP	GO:0042531	positive regulation of tyrosine phosphorylation of STAT protein
BP	IEA	GO:0043065	positive regulation of apoptotic process
BP	IBA	GO:0043066	negative regulation of apoptotic process
BP	IEA	GO:0043066	negative regulation of apoptotic process
BP	IBA	GO:0043410	positive regulation of MAPK cascade
BP	IMP	GO:0043653	mitochondrial fragmentation involved in apoptotic process
BP	IEA	GO:0045165	cell fate commitment
BP	IMP	GO:0045893	positive regulation of transcription, DNA-templated
BP	IMP	GO:0046427	positive regulation of JAK-STAT cascade
BP	IDA	GO:0046777	protein autophosphorylation
BP	IEA	GO:0046854	phosphatidylinositol phosphorylation
BP	TAS	GO:0051897	positive regulation of protein kinase B signaling
BP	ISS	GO:0060045	positive regulation of cardiac muscle cell proliferation
BP	ISS	GO:0060644	mammary gland epithelial cell differentiation
BP	ISS	GO:0060749	mammary gland alveolus development
BP	ISS	GO:0061026	cardiac muscle tissue regeneration
BP	IBA	GO:0070374	positive regulation of ERK1 and ERK2 cascade
BP	IMP	GO:0070374	positive regulation of ERK1 and ERK2 cascade
BP	IEA	GO:0071364	cellular response to epidermal growth factor stimulus
BP	IEA	GO:2000010	positive regulation of protein localization to cell surface
BP	TAS	GO:2000145	regulation of cell motility
BP	IEA	GO:2001223	negative regulation of neuron migration
CC	TAS	GO:0005576	extracellular region
CC	IDA	GO:0005634	nucleus
CC	TAS	GO:0005654	nucleoplasm
CC	IBA	GO:0005737	cytoplasm
CC	IDA	GO:0005739	mitochondrion
CC	TAS	GO:0005759	mitochondrial matrix
CC	TAS	GO:0005829	cytosol
CC	TAS	GO:0005886	plasma membrane
CC	IBA	GO:0005887	integral component of plasma membrane
CC	IBA	GO:0009925	basal plasma membrane
CC	IEA	GO:0016021	integral component of membrane
CC	IDA	GO:0016323	basolateral plasma membrane
CC	IBA	GO:0043235	receptor complex
CC	IDA	GO:0043235	receptor complex
MF	IBA	GO:0004709	MAP kinase kinase kinase activity
MF	IBA	GO:0004713	protein tyrosine kinase activity
MF	IDA	GO:0004713	protein tyrosine kinase activity
MF	TAS	GO:0004713	protein tyrosine kinase activity
MF	IBA	GO:0004714	transmembrane receptor protein tyrosine kinase activity
MF	IDA	GO:0004714	transmembrane receptor protein tyrosine kinase activity
MF	IBA	GO:0004888	transmembrane signaling receptor activity
MF	TAS	GO:0005088	Ras guanyl-nucleotide exchange factor activity
MF	IBA	GO:0005154	epidermal growth factor receptor binding
MF	IPI	GO:0005154	epidermal growth factor receptor binding
MF	IPI	GO:0005515	protein binding
MF	IEA	GO:0005524	ATP binding
MF	IBA	GO:0031434	mitogen-activated protein kinase kinase binding
MF	IPI	GO:0042803	protein homodimerization activity
MF	IMP	GO:0044212	transcription regulatory region DNA binding
MF	TAS	GO:0046934	phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Gene expression in normal tissue: ERBB4

Select Project:

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in ERBB4

Database	Pathway ID	Pathway Des.
reactome	R-HSA-1227986	Signaling by ERBB2
reactome	R-HSA-1227986	Signaling by ERBB2
reactome	R-HSA-1236394	Signaling by ERBB4
reactome	R-HSA-1236394	Signaling by ERBB4
reactome	R-HSA-1250196	SHC1 events in ERBB2 signaling
reactome	R-HSA-1250196	SHC1 events in ERBB2 signaling
reactome	R-HSA-1250342	PI3K events in ERBB4 signaling
reactome	R-HSA-1250347	SHC1 events in ERBB4 signaling
reactome	R-HSA-1251985	Nuclear signaling by ERBB4
reactome	R-HSA-1251985	Nuclear signaling by ERBB4
reactome	R-HSA-1253288	Downregulation of ERBB4 signaling
reactome	R-HSA-1257604	PIP3 activates AKT signaling
reactome	R-HSA-162582	Signal Transduction
reactome	R-HSA-162582	Signal Transduction
reactome	R-HSA-1643685	Disease
reactome	R-HSA-1963640	GRB2 events in ERBB2 signaling
reactome	R-HSA-1963642	PI3K events in ERBB2 signaling
reactome	R-HSA-199418	Negative regulation of the PI3K/AKT network
reactome	R-HSA-2219528	PI3K/AKT Signaling in Cancer
reactome	R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
reactome	R-HSA-5663202	Diseases of signal transduction
reactome	R-HSA-5673001	RAF/MAP kinase cascade
reactome	R-HSA-5683057	MAPK family signaling cascades
reactome	R-HSA-5684996	MAPK1/MAPK3 signaling
reactome	R-HSA-6785631	ERBB2 Regulates Cell Motility
reactome	R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
reactome	R-HSA-8847993	ERBB2 Activates PTK6 Signaling
reactome	R-HSA-8848021	Signaling by PTK6
reactome	R-HSA-8863795	Downregulation of ERBB2 signaling
reactome	R-HSA-8939211	ESR-mediated signaling
reactome	R-HSA-9006925	Intracellular signaling by second messengers
reactome	R-HSA-9006927	Signaling by Non-Receptor Tyrosine Kinases
reactome	R-HSA-9006931	Signaling by Nuclear Receptors
reactome	R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
reactome	R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
reactome	R-HSA-9018519	Estrogen-dependent gene expression
biocarta	erbb4pathway	g-secretase mediated erbb4 signaling pathway
biocarta	her2pathway	role of erbb2 in signal transduction and oncology
pharmgkb	PA162356267	EGFR Inhibitor Pathway, Pharmacodynamics
pid	erbb4_pathway	ErbB4 signaling events
pid	erbb_network_pathway	ErbB receptor signaling network
netpath	Pathway_Prolactin	Prolactin
kegg	hsa04010	MAPK signaling pathway - Homo sapiens (human)
kegg	hsa04012	ErbB signaling pathway - Homo sapiens (human)
kegg	hsa04020	Calcium signaling pathway - Homo sapiens (human)
kegg	hsa04151	PI3K-Akt signaling pathway - Homo sapiens (human)
kegg	hsa05205	Proteoglycans in cancer - Homo sapiens (human)
wikipathways	WP3297	EV release from cardiac cells and their functional effects
wikipathways	WP3680	Association Between Physico-Chemical Features and Toxicity Associated Pathways
wikipathways	WP673	ErbB Signaling Pathway

Gene-Drug: Aster Plot

Drug ID	Drug Name	Model Num.
iGMDRD427	ABT737	2
iGMDRD546	BMS-754807	4
iGMDRD781	Sirolimus	2
iGMDRD126	Tipifarnib	1
iGMDRD433	Lexibulin	4
iGMDRD151	CHM-1	5
iGMDRD599	Salermide	1
iGMDRD772	BRD4770	2
iGMDRD425	ERASTIN	2
iGMDRD579	PF750	2
iGMDRD297	Austocystin D	6
iGMDRD394	BX-795	3
iGMDRD446	LY 2183240	4
iGMDRD201	SKI II	2
iGMDRD193	Fqi1	9
iGMDRD782	DC-45-A2	4
iGMDRD318	PAC-1	3
iGMDRD885	Compound 110	2
iGMDRD801	2,4-dideoxy-DC-45-A2	2
iGMDRD52	Rotenone	2
iGMDRD187	BRD9876	3
iGMDRD870	BRD63610	2
iGMDRD270	Ciclosporin	1
iGMDRD260	FQI-2	3
iGMDRD255	SB225002	1
iGMDRD64	Parbendazole	7
iGMDRD451	Serdemetan	2
iGMDRD100	Zebularine	2
iGMDRD188	Piperlongumine	2
iGMDRD133	Lapatinib	15
iGMDRD74	Idarubicin	3
iGMDRD888	Compound 44	7
iGMDRD506	Fedratinib	1
iGMDRD562	Navitoclax	2
iGMDRD780	PP-30	2
iGMDRD424	Tamatinib	4
iGMDRD701	NVP-AUY922	2
iGMDRD84	Lovastatin acid	2
iGMDRD307	Manumycin A	2
iGMDRD1020	Trastuzumab	2
iGMDRD901	ELCPK	5
iGMDRD211	(1S,3R)-RSL3	2
iGMDRD123	Isoevodiamine	6
iGMDRD154	NSC23766	4
iGMDRD351	GW843682X	4
iGMDRD698	Neratinib	3
iGMDRD237	ABT-751	2
iGMDRD705	Nakiterpiosin	2
iGMDRD103	SN-38	2
iGMDRD121	GMX1778	3
iGMDRD137	Indisulam	2
iGMDRD158	NSC141540	7
iGMDRD278	TTNPB	2
iGMDRD505	Pevonedistat	1
iGMDRD300	Tozasertib	2
iGMDRD246	NPC26	3
iGMDRD322	FK 866	4
iGMDRD414	MST-312	1
iGMDRD286	Nsc 632839	2
iGMDRD367	Ro 28-1675	3
iGMDRD329	Merck60	2

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in ERBB4

SITE

DATATYPES

CLASSFICATION

Disclaimer: iGMDR is intended for research purposes only. Its information cannot be used for emergencies or medical or professional advice.