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

    Gene ID: 2066, updated on 30-Oct-2024

    Summary

    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 MIM:600543; AllianceGenome:HGNC:3432
    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]
    Expression
    Biased expression in kidney (RPKM 3.0), brain (RPKM 2.7) and 8 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See ERBB4 in Genome Data Viewer
    Location:
    2q34
    Exon count:
    31
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (211375717..212538802, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (211856201..213019445, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (212240442..213403526, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene 5'-nucleotidase domain containing 2 pseudogene Neighboring gene NANOG hESC enhancer GRCh37_chr2:211994958-211995459 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:212092893-212093684 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:212093685-212094476 Neighboring gene VISTA enhancer hs1578 Neighboring gene ribosomal protein S27 pseudogene 10 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:212278303-212278804 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:212278805-212279304 Neighboring gene NANOG hESC enhancer GRCh37_chr2:212363277-212363781 Neighboring gene RNA, 5S ribosomal pseudogene 119 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:212631258-212631794 Neighboring gene MT-ND2 pseudogene 23 Neighboring gene MT-CO1 pseudogene 46 Neighboring gene uncharacterized LOC124906116 Neighboring gene NANOG hESC enhancer GRCh37_chr2:213291716-213292249 Neighboring gene microRNA 548f-2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:213402057-213402557 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17056 Neighboring gene long intergenic non-protein coding RNA 1878 Neighboring gene PC-esterase domain containing 1C, pseudogene

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Amyotrophic lateral sclerosis type 19 Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2024-10-23)

    ClinGen Genome Curation Page
    Haploinsufficency

    Little evidence for dosage pathogenicity (Last evaluated 2024-10-23)

    ClinGen Genome Curation PagePubMed

    EBI 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.
    EBI GWAS Catalog
    Genetics of coronary artery calcification among African Americans, a meta-analysis.
    EBI GWAS Catalog
    Genome-wide association studies and heritability estimates of body mass index related phenotypes in bangladeshi adults.
    EBI GWAS Catalog
    Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations.
    EBI GWAS Catalog
    Genome-wide association study of the five-factor model of personality in young Korean women.
    EBI GWAS Catalog
    Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality.
    EBI GWAS Catalog
    Genome-wide interaction studies reveal sex-specific asthma risk alleles.
    EBI GWAS Catalog
    New susceptibility loci associated with kidney disease in type 1 diabetes.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC138404

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables GABA receptor binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables epidermal growth factor receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables epidermal growth factor receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables epidermal growth factor receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables neuregulin receptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein tyrosine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables transcription cis-regulatory region binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    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 
    Process Evidence Code Pubs
    involved_in ERBB2-ERBB4 signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in ERBB4 signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in ERBB4-ERBB4 signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cardiac muscle tissue regeneration ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cell fate commitment IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cell migration IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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 IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cell surface receptor signaling pathway via JAK-STAT IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to epidermal growth factor stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in central nervous system morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in embryonic pattern specification ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in epidermal growth factor receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in establishment of planar polarity involved in nephron morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in heart development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in lactation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in mammary gland alveolus development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in mammary gland epithelial cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in mitochondrial fragmentation involved in apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    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 IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of cell population proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of neuron migration IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in nervous system development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in neural crest cell migration ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in neurogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in neurotransmitter receptor localization to postsynaptic specialization membrane IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in olfactory bulb interneuron differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in peptidyl-tyrosine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of DNA-templated transcription IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of ERK1 and ERK2 cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of cardiac muscle cell proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of cell population proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of cell population proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of protein localization to cell surface IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of protein phosphorylation TAS
    Traceable Author Statement
    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 tyrosine phosphorylation of STAT protein IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of cell migration ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in synapse assembly IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    located_in GABA-ergic synapse IEA
    Inferred from Electronic Annotation
    more info
     
    is_active_in basal plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in basolateral plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in extracellular region TAS
    Traceable Author Statement
    more info
     
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
     
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
     
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in neuromuscular junction IEA
    Inferred from Electronic Annotation
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    located_in postsynaptic density membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in postsynaptic membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in presynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
     
    part_of receptor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of receptor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    receptor tyrosine-protein kinase erbB-4
    Names
    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
    XP_005246433.1
    XP_005246434.1
    XP_006712427.1
    XP_016859066.1
    XP_016859067.1
    XP_016859068.1
    XP_016859069.1
    XP_016859070.1
    XP_016859071.1
    XP_054196992.1
    XP_054196993.1
    XP_054196994.1
    XP_054196995.1
    XP_054196996.1
    XP_054196997.1
    XP_054196998.1
    XP_054196999.1
    XP_054197000.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_011805.2 RefSeqGene

      Range
      4827..1167912
      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 identical proteins and their annotated locations for 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
      Related
      ENSP00000403204.1, ENST00000436443.5
      Conserved Domains (5) 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
      pfam00757
      Location:186332
      Furin-like; Furin-like cysteine rich region
      pfam01030
      Location:55167
      Recep_L_domain; Receptor L domain
      pfam14843
      Location:502634
      GF_recep_IV; Growth factor receptor domain IV
    2. NM_005235.3NP_005226.1  receptor tyrosine-protein kinase erbB-4 isoform JM-a/CVT-1 precursor

      See identical proteins and their annotated locations for 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, AC096765, AI793060, BQ015804, CR627023, L07868
      Consensus CDS
      CCDS2394.1
      UniProtKB/Swiss-Prot
      B7ZLD7, B7ZLE2, B7ZLE3, Q15303, Q2M1W1, Q59EW4
      Related
      ENSP00000342235.4, ENST00000342788.9
      Conserved Domains (5) 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
      pfam00757
      Location:186332
      Furin-like; Furin-like cysteine rich region
      pfam01030
      Location:55167
      Recep_L_domain; Receptor L domain
      pfam14843
      Location:502634
      GF_recep_IV; Growth factor receptor domain IV

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      211375717..212538802 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005246377.4XP_005246434.1  receptor tyrosine-protein kinase erbB-4 isoform X8

      See identical proteins and their annotated locations for XP_005246434.1

      Related
      ENSP00000260943.7, ENST00000260943.11
      Conserved Domains (5) 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
      pfam00757
      Location:186332
      Furin-like; Furin-like cysteine rich region
      pfam01030
      Location:55167
      Recep_L_domain; Receptor L domain
      pfam14843
      Location:502634
      GF_recep_IV; Growth factor receptor domain IV
    2. XM_005246376.4XP_005246433.1  receptor tyrosine-protein kinase erbB-4 isoform X7

      See identical proteins and their annotated locations for XP_005246433.1

      Conserved Domains (5) 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
      pfam00757
      Location:186332
      Furin-like; Furin-like cysteine rich region
      pfam01030
      Location:55167
      Recep_L_domain; Receptor L domain
      pfam14843
      Location:502634
      GF_recep_IV; Growth factor receptor domain IV
    3. XM_006712364.4XP_006712427.1  receptor tyrosine-protein kinase erbB-4 isoform X5

      Conserved Domains (8) 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
      smart00261
      Location:549596
      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:186332
      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_017003581.3XP_016859070.1  receptor tyrosine-protein kinase erbB-4 isoform X6

    5. XM_017003578.3XP_016859067.1  receptor tyrosine-protein kinase erbB-4 isoform X2

    6. XM_017003580.3XP_016859069.1  receptor tyrosine-protein kinase erbB-4 isoform X4

    7. XM_017003579.3XP_016859068.1  receptor tyrosine-protein kinase erbB-4 isoform X3

    8. XM_017003577.3XP_016859066.1  receptor tyrosine-protein kinase erbB-4 isoform X1

    9. XM_017003582.2XP_016859071.1  receptor tyrosine-protein kinase erbB-4 isoform X9

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      211856201..213019445 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054341024.1XP_054196999.1  receptor tyrosine-protein kinase erbB-4 isoform X8

    2. XM_054341023.1XP_054196998.1  receptor tyrosine-protein kinase erbB-4 isoform X7

    3. XM_054341021.1XP_054196996.1  receptor tyrosine-protein kinase erbB-4 isoform X5

    4. XM_054341022.1XP_054196997.1  receptor tyrosine-protein kinase erbB-4 isoform X6

    5. XM_054341018.1XP_054196993.1  receptor tyrosine-protein kinase erbB-4 isoform X2

    6. XM_054341020.1XP_054196995.1  receptor tyrosine-protein kinase erbB-4 isoform X4

    7. XM_054341019.1XP_054196994.1  receptor tyrosine-protein kinase erbB-4 isoform X3

    8. XM_054341017.1XP_054196992.1  receptor tyrosine-protein kinase erbB-4 isoform X1

    9. XM_054341025.1XP_054197000.1  receptor tyrosine-protein kinase erbB-4 isoform X9