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ERBB4 erb-b2 receptor tyrosine kinase 4 [ Homo sapiens (human) ]

Gene ID: 2066, updated on 22-Feb-2015
Official Symbol
ERBB4provided by HGNC
Official Full Name
erb-b2 receptor tyrosine kinase 4provided by HGNC
Primary source
HGNC:HGNC:3432
See related
Ensembl:ENSG00000178568; HPRD:02767; MIM:600543; Vega:OTTHUMG00000133012
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HER4; ALS19; p180erbB4
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]
Orthologs
See ERBB4 in MapViewer
Location:
2q33.3-q34
Exon count:
29
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 2 NC_000002.12 (211375717..212539155, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (212240442..213403879, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene 5'-nucleotidase domain containing 2 pseudogene Neighboring gene ribosomal protein S27 pseudogene 10 Neighboring gene RNA, 5S ribosomal pseudogene 119 Neighboring gene MT-ND2 pseudogene 23 Neighboring gene microRNA 548f-2 Neighboring gene PC-esterase domain containing 1C, pseudogene Neighboring gene microRNA 4776-1 Neighboring gene microRNA 4776-2

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Amyotrophic lateral sclerosis 19 Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study.
NHGRI GWA Catalog
Genetics of coronary artery calcification among African Americans, a meta-analysis.
NHGRI GWA Catalog
Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
NHGRI GWA Catalog
Genome-wide association study of the five-factor model of personality in young Korean women.
NHGRI GWA Catalog
Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality.
NHGRI GWA Catalog
Genome-wide interaction studies reveal sex-specific asthma risk alleles.
NHGRI GWA Catalog
New susceptibility loci associated with kidney disease in type 1 diabetes.
NHGRI GWA Catalog
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    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
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    SHC1 events in ERBB2 signaling, organism-specific biosystemAll ERBB2 heterodimers, ERBB2:EGFR, ERBB2:ERBB3 and ERBB2:ERBB4, are able to activate RAF/MAP kinase cascade by recruiting SHC1 (Pinkas-Kramarski et al. 1996, Sepp-Lorenzino et al. 1996) to phosphory...
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    SHC1 events in ERBB4 signaling, organism-specific biosystemAll splicing isoforms of ERBB4 possess two tyrosine residues in the C-tail that serve as docking sites for SHC1 (Kaushansky et al. 2008, Pinkas-Kramarski et al. 1996, Cohen et al. 1996). Once bound t...
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Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC138404

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
epidermal growth factor receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
protein tyrosine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
receptor signaling protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
 
transcription regulatory region DNA binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
transmembrane receptor protein tyrosine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
 
cardiac muscle tissue regeneration ISS
Inferred from Sequence or Structural Similarity
more info
 
cell fate commitment IEA
Inferred from Electronic Annotation
more info
 
cell migration IDA
Inferred from Direct Assay
more info
PubMed 
cell proliferation TAS
Traceable Author Statement
more info
PubMed 
central nervous system morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
embryonic pattern specification ISS
Inferred from Sequence or Structural Similarity
more info
 
epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
fibroblast growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
heart development ISS
Inferred from Sequence or Structural Similarity
more info
 
innate immune response TAS
Traceable Author Statement
more info
 
lactation IMP
Inferred from Mutant Phenotype
more info
PubMed 
mammary gland alveolus development ISS
Inferred from Sequence or Structural Similarity
more info
 
mammary gland epithelial cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
mitochondrial fragmentation involved in apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
nervous system development ISS
Inferred from Sequence or Structural Similarity
more info
 
neural crest cell migration ISS
Inferred from Sequence or Structural Similarity
more info
 
neurotrophin TRK receptor signaling pathway TAS
Traceable Author Statement
more info
 
olfactory bulb interneuron differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
peptidyl-tyrosine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
phosphatidylinositol-mediated signaling TAS
Traceable Author Statement
more info
 
positive regulation of ERK1 and ERK2 cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of STAT protein import into nucleus IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cardiac muscle cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of phosphatidylinositol 3-kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
NOT positive regulation of phosphatidylinositol 3-kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of protein phosphorylation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of tyrosine phosphorylation of Stat5 protein IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of cell migration ISS
Inferred from Sequence or Structural Similarity
more info
 
signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
signal transduction by phosphorylation IEA
Inferred from Electronic Annotation
more info
 
transcription, DNA-templated IEA
Inferred from Electronic Annotation
more info
 
transmembrane receptor protein tyrosine kinase signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
basolateral plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
extracellular region TAS
Traceable Author Statement
more info
 
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
mitochondrial matrix TAS
Traceable Author Statement
more info
 
mitochondrion IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
receptor complex IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
receptor tyrosine-protein kinase erbB-4
Names
receptor tyrosine-protein kinase erbB-4
avian erythroblastic leukemia viral (v-erb-b2) oncogene homolog 4
human epidermal growth factor receptor 4
proto-oncogene-like protein c-ErbB-4
tyrosine kinase-type cell surface receptor HER4
v-erb-a erythroblastic leukemia viral oncogene homolog 4
v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4
NP_001036064.1
NP_005226.1

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.

Genomic

  1. NG_011805.1 RefSeqGene

    Range
    5001..1167911
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001042599.1NP_001036064.1  receptor tyrosine-protein kinase erbB-4 isoform JM-a/CVT-2 precursor

    See proteins identical to NP_001036064.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (JM-a/CYT-2) lacks an alternate in-frame exon, compared to variant JM-a/CYT-1, resulting in a shorter protein (isoform JM-a/CYT-2) that lacks the phosphotidylinositol-3 kinase binding site, compared to isoform JM-a/CYT-1.
    Source sequence(s)
    AB209697, AC012069, AI793060, BC112199, BQ015804, L07868
    Consensus CDS
    CCDS42811.1
    UniProtKB/Swiss-Prot
    Q15303
    Related
    ENSP00000403204, OTTHUMP00000206623, ENST00000436443, OTTHUMT00000336976
    Conserved Domains (8) summary
    cd05110
    Location:7101012
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:642685
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    smart00261
    Location:611634
    FU; Furin-like repeats
    cd00064
    Location:229274
    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:186334
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam07714
    Location:718974
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV
  2. NM_005235.2NP_005226.1  receptor tyrosine-protein kinase erbB-4 isoform JM-a/CVT-1 precursor

    See proteins identical to NP_005226.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (JM-a/CYT-1) represents the longer transcript and encodes the longer isoform (JM-a/CYT-1).
    Source sequence(s)
    AC012069, AI793060, BQ015804, CR627023, L07868
    Consensus CDS
    CCDS2394.1
    UniProtKB/Swiss-Prot
    Q15303
    Related
    ENSP00000342235, OTTHUMP00000163968, ENST00000342788, OTTHUMT00000256597
    Conserved Domains (8) summary
    cd05110
    Location:7101012
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:642685
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    smart00261
    Location:611634
    FU; Furin-like repeats
    cd00064
    Location:229274
    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:186334
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam07714
    Location:718974
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38 Primary Assembly

    Range
    211375717..212539155
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005246377.1XP_005246434.1  

    See proteins identical to XP_005246434.1

    UniProtKB/Swiss-Prot
    Q15303
    Conserved Domains (7) summary
    cd05110
    Location:7001002
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:632675
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    cd00064
    Location:229274
    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:186334
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam07714
    Location:708964
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV
  2. XM_005246376.1XP_005246433.1  

    See proteins identical to XP_005246433.1

    UniProtKB/Swiss-Prot
    Q15303
    Conserved Domains (7) summary
    cd05110
    Location:7001002
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:632675
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    cd00064
    Location:229274
    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:186334
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam07714
    Location:708964
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV
  3. XM_005246375.1XP_005246432.1  

    Conserved Domains (7) summary
    cd05110
    Location:7251027
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:657700
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    cd00064
    Location:229274
    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:186334
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam07714
    Location:733989
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV
  4. XM_006712364.1XP_006712427.1  

    Conserved Domains (7) summary
    cd05110
    Location:7251027
    PTKc_HER4; Catalytic domain of the Protein Tyrosine Kinase, HER4
    cd12092
    Location:657700
    TM_ErbB4; Transmembrane domain of ErbB4, a Protein Tyrosine Kinase
    cd00064
    Location:229274
    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:186334
    Furin-like; Furin-like cysteine rich region
    pfam01030
    Location:55167
    Recep_L_domain; Receptor L domain
    pfam07714
    Location:733989
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14843
    Location:502634
    GF_recep_IV; Growth factor receptor domain IV

Alternate CHM1_1.1

Genomic

  1. NC_018913.2 Alternate CHM1_1.1

    Range
    212246189..213409602
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000134.1 Alternate HuRef

    Range
    204087816..205252852
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)