Erbb4 erb-b2 receptor tyrosine kinase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Erbb4provided by MGI
Official Full Name: erb-b2 receptor tyrosine kinase 4provided by MGI
Primary source: MGI:MGI:104771
See related: Ensembl:ENSMUSG00000062209 AllianceGenome:MGI:104771
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Her4; c-erbB-4
Summary: Enables protein tyrosine kinase activity. Involved in several processes, including mammary gland development; nervous system development; and positive regulation of nitrogen compound metabolic process. Acts upstream of or within several processes, including cellular response to epidermal growth factor stimulus; peptidyl-tyrosine autophosphorylation; and regulation of apoptotic process. Located in GABA-ergic synapse and glutamatergic synapse. Is integral component of postsynaptic density membrane. Is integral component of presynaptic membrane. Is expressed in several structures, including brain; early conceptus; embryo ectoderm; heart; and mammary gland primordium. Human ortholog(s) of this gene implicated in amyotrophic lateral sclerosis type 19; colorectal cancer; esophagus squamous cell carcinoma; hepatocellular carcinoma; and lung adenocarcinoma. Orthologous to human ERBB4 (erb-b2 receptor tyrosine kinase 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in CNS E18 (RPKM 2.3), frontal lobe adult (RPKM 2.1) and 8 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 C3; 1 33.8 cM

Exon count:: 33

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (68071063..69147756, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (68031884..69108576, complement)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

nNOS in Erbb4-positive neurons regulates GABAergic transmission in mouse hippocampus.
Title: nNOS in Erbb4-positive neurons regulates GABAergic transmission in mouse hippocampus.
Parvalbumin interneurons dysfunction is potentially associated with FalphaMNs decrease and NRG1-ErbB4 signaling inhibition in spinal cord in amyotrophic lateral sclerosis.
Title: Parvalbumin interneurons dysfunction is potentially associated with FαMNs decrease and NRG1-ErbB4 signaling inhibition in spinal cord in amyotrophic lateral sclerosis.
ErbB4 affects Th1/Th17 cell differentiation and promotes psoriasis progression.
Title: ErbB4 affects Th1/Th17 cell differentiation and promotes psoriasis progression.
Developmental loss of ErbB4 in PV interneurons disrupts state-dependent cortical circuit dynamics.
Title: Developmental loss of ErbB4 in PV interneurons disrupts state-dependent cortical circuit dynamics.
Energy Expenditure Homeostasis Requires ErbB4, an Obesity Risk Gene, in the Paraventricular Nucleus.
Title: Energy Expenditure Homeostasis Requires ErbB4, an Obesity Risk Gene, in the Paraventricular Nucleus.
An Unbiased Functional Genetics Screen Identifies Rare Activating ERBB4 Mutations.
Title: An Unbiased Functional Genetics Screen Identifies Rare Activating ERBB4 Mutations.
miR-433 Inhibits Glioblastoma Progression by Suppressing the PI3K/Akt Signaling Pathway Through Direct Targeting of ERBB4.
Title: miR-433 Inhibits Glioblastoma Progression by Suppressing the PI3K/Akt Signaling Pathway Through Direct Targeting of ERBB4.
Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis.
Title: Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis.
Erbb4 Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes.
Title: Erbb4 Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes.
The laterodorsal tegmentum-ventral tegmental area circuit controls depression-like behaviors by activating ErbB4 in DA neurons.
Title: The laterodorsal tegmentum-ventral tegmental area circuit controls depression-like behaviors by activating ErbB4 in DA neurons.

Submit: New GeneRIF Correction See all GeneRIFs (139)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (7) 1 citation
Targeted (8) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1Mit178 (e-PCR), detects polymorphism
- UniSTS:128516

Erbb4 (e-PCR), detects polymorphism
- UniSTS:468004

NoName (e-PCR)
- UniSTS:548400

AU049543 (e-PCR)
- UniSTS:145990

NoName (e-PCR)
- UniSTS:224383

Erbb4 (e-PCR), detects polymorphism
- UniSTS:143005

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables GABA receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables epidermal growth factor receptor activity	IGI Inferred from Genetic Interaction more info	PubMed
enables epidermal growth factor receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables epidermal growth factor receptor binding	ISO Inferred from Sequence Orthology more info
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables neuregulin binding	ISO Inferred from Sequence Orthology more info	PubMed
enables neuregulin receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables neuregulin receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables neuregulin receptor activity	ISO Inferred from Sequence Orthology more info	PubMed
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	ISO Inferred from Sequence Orthology more info
enables transcription cis-regulatory region binding	ISO Inferred from Sequence Orthology more info
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane receptor protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane receptor protein tyrosine kinase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in ERBB2-ERBB4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in ERBB2-ERBB4 signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in ERBB4 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ERBB4 signaling pathway	ISO Inferred from Sequence Orthology more info	PubMed
involved_in ERBB4-ERBB4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in ERBB4-ERBB4 signaling pathway	ISO Inferred from Sequence Orthology more info	PubMed
acts_upstream_of_or_within apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in cardiac muscle tissue regeneration	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cell fate commitment	IDA Inferred from Direct Assay more info	PubMed
involved_in cell migration	ISO Inferred from Sequence Orthology more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in cell surface receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in cell surface receptor signaling pathway via JAK-STAT	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to epidermal growth factor stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in central nervous system morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic pattern specification	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within establishment of planar polarity involved in nephron morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within heart development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lactation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lactation	ISO Inferred from Sequence Orthology more info
involved_in mammary gland alveolus development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mammary gland epithelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial fragmentation involved in apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neural crest cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neurogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in neurotransmitter receptor localization to postsynaptic specialization membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in neurotransmitter receptor localization to postsynaptic specialization membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in olfactory bulb interneuron differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cardiac muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell population proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of epithelial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of glucose import	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of kinase activity	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of phospholipid biosynthetic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of protein localization to cell surface	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of receptor signaling pathway via JAK-STAT	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of receptor signaling pathway via JAK-STAT	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of synaptic transmission, GABAergic	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of tyrosine phosphorylation of STAT protein	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of tyrosine phosphorylation of STAT protein	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	ISO Inferred from Sequence Orthology more info
involved_in surfactant homeostasis	ISO Inferred from Sequence Orthology more info
involved_in synapse assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in synapse assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synapse maturation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in GABA-ergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in GABA-ergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in basal plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in basolateral plasma membrane	ISO Inferred from Sequence Orthology more info
located_in caveola	ISO Inferred from Sequence Orthology more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with inhibitory synapse	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
is_active_in neuromuscular junction	IDA Inferred from Direct Assay more info	PubMed
is_active_in neuromuscular junction	IMP Inferred from Mutant Phenotype more info	PubMed
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info	PubMed
is_active_in postsynaptic density membrane	IDA Inferred from Direct Assay more info	PubMed
located_in postsynaptic membrane	ISO Inferred from Sequence Orthology more info
is_active_in presynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of receptor complex	ISO Inferred from Sequence Orthology more info	PubMed

General protein information

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Preferred Names: receptor tyrosine-protein kinase erbB-4

Names: avian erythroblastosis oncogene B 4; proto-oncogene-like protein c-ErbB-4; v-erb-a erythroblastic leukemia viral oncogene homolog 4

NP_034284.1

EC 2.7.10.1

XP_006495755.1

EC 2.7.10.1

XP_006495756.1

EC 2.7.10.1

XP_006495757.1

EC 2.7.10.1

XP_006495758.1

EC 2.7.10.1

XP_036015359.1

EC 2.7.10.1

XP_036015364.1

EC 2.7.10.1

XP_036015388.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_010154.2 → NP_034284.1 receptor tyrosine-protein kinase erbB-4 precursor

See identical proteins and their annotated locations for NP_034284.1

Status: VALIDATED

Source sequence(s)

AC167658, AK144050

Consensus CDS

CCDS48285.1

UniProtKB/Swiss-Prot

Q61527

Related

ENSMUSP00000114123.2, ENSMUST00000121473.8

Conserved Domains (8) summary

cd05110
Location:710 → 1012

PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4

cd12092
Location:642 → 685

TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase

smart00261
Location:549 → 596

FU; Furin-like repeats

cd00064
Location:229 → 274

FU; Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.

pfam00757
Location:186 → 332

Furin-like; Furin-like cysteine rich region

pfam01030
Location:55 → 167

Recep_L_domain; Receptor L domain

pfam07714
Location:718 → 974

Pkinase_Tyr; Protein tyrosine kinase

pfam14843
Location:502 → 634

GF_recep_IV; Growth factor receptor domain IV

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000067.7 Reference GRCm39 C57BL/6J

Range

68071063..69147756 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006495692.5 → XP_006495755.1 receptor tyrosine-protein kinase erbB-4 isoform X1

See identical proteins and their annotated locations for XP_006495755.1

UniProtKB/Swiss-Prot

B2KGF5, B2KGF6, O88460, Q3UNS6, Q61527

Related

ENSMUSP00000112713.2, ENSMUST00000119142.8

Conserved Domains (5) summary

cd05110
Location:710 → 1012

PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4

cd12092
Location:642 → 685

TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase

pfam00757
Location:186 → 334

Furin-like; Furin-like cysteine rich region

pfam01030
Location:55 → 165

Recep_L_domain; Receptor L domain

pfam14843
Location:502 → 634

GF_recep_IV; Growth factor receptor domain IV
XM_006495694.5 → XP_006495757.1 receptor tyrosine-protein kinase erbB-4 isoform X3

Conserved Domains (5) summary

cd05110
Location:700 → 1002

PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4

cd12092
Location:632 → 675

TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase

pfam00757
Location:186 → 334

Furin-like; Furin-like cysteine rich region

pfam01030
Location:55 → 165

Recep_L_domain; Receptor L domain

pfam14843
Location:502 → 634

GF_recep_IV; Growth factor receptor domain IV
XM_006495693.5 → XP_006495756.1 receptor tyrosine-protein kinase erbB-4 isoform X2

See identical proteins and their annotated locations for XP_006495756.1

UniProtKB/Swiss-Prot

Q61527

Conserved Domains (5) summary

cd05110
Location:700 → 1002

PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4

cd12092
Location:632 → 675

TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase

pfam00757
Location:186 → 334

Furin-like; Furin-like cysteine rich region

pfam01030
Location:55 → 165

Recep_L_domain; Receptor L domain

pfam14843
Location:502 → 634

GF_recep_IV; Growth factor receptor domain IV
XM_006495695.5 → XP_006495758.1 receptor tyrosine-protein kinase erbB-4 isoform X6

UniProtKB/TrEMBL

B2KGF7

Conserved Domains (5) summary

cd12092
Location:642 → 685

TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase

pfam00757
Location:186 → 334

Furin-like; Furin-like cysteine rich region

pfam01030
Location:55 → 165

Recep_L_domain; Receptor L domain

pfam14843
Location:502 → 634

GF_recep_IV; Growth factor receptor domain IV

cl21453
Location:710 → 829

PKc_like; Protein Kinases, catalytic domain
XM_036159471.1 → XP_036015364.1 receptor tyrosine-protein kinase erbB-4 isoform X5

UniProtKB/TrEMBL

B2KGF7

Conserved Domains (5) summary

cd12092
Location:642 → 685

TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase

pfam00757
Location:186 → 332

Furin-like; Furin-like cysteine rich region

pfam01030
Location:55 → 167

Recep_L_domain; Receptor L domain

pfam14843
Location:502 → 634

GF_recep_IV; Growth factor receptor domain IV

cl21453
Location:710 → 834

PKc_like; Protein Kinases, catalytic domain
XM_036159466.1 → XP_036015359.1 receptor tyrosine-protein kinase erbB-4 isoform X4

UniProtKB/TrEMBL

B2KGF7

Conserved Domains (5) summary

cd12092
Location:642 → 685

TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase

pfam00757
Location:186 → 332

Furin-like; Furin-like cysteine rich region

pfam01030
Location:55 → 167

Recep_L_domain; Receptor L domain

pfam14843
Location:502 → 634

GF_recep_IV; Growth factor receptor domain IV

cl21453
Location:710 → 829

PKc_like; Protein Kinases, catalytic domain
XM_036159495.1 → XP_036015388.1 receptor tyrosine-protein kinase erbB-4 isoform X7

UniProtKB/TrEMBL

B2KGF7

Related

ENSMUSP00000115373.2, ENSMUST00000153432.2

Conserved Domains (3) summary

pfam00757
Location:186 → 332

Furin-like; Furin-like cysteine rich region

pfam01030
Location:55 → 167

Recep_L_domain; Receptor L domain

pfam14843
Location:502 → 634

GF_recep_IV; Growth factor receptor domain IV