Human Gene ERBB4 (ENST00000342788.9) from GENCODE V44
  Description: Homo sapiens erb-b2 receptor tyrosine kinase 4 (ERBB4), transcript variant JM-a/CVT-1, mRNA. (from RefSeq NM_005235)
RefSeq Summary (NM_005235): 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].
Gencode Transcript: ENST00000342788.9
Gencode Gene: ENSG00000178568.16
Transcript (Including UTRs)
   Position: hg38 chr2:211,375,717-212,538,802 Size: 1,163,086 Total Exon Count: 28 Strand: -
Coding Region
   Position: hg38 chr2:211,383,615-212,538,530 Size: 1,154,916 Coding Exon Count: 28 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:211,375,717-212,538,802)mRNA (may differ from genome)Protein (1308 aa)
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HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: ERBB4_HUMAN
DESCRIPTION: RecName: Full=Receptor tyrosine-protein kinase erbB-4; EC=2.7.10.1; AltName: Full=Proto-oncogene-like protein c-ErbB-4; AltName: Full=Tyrosine kinase-type cell surface receptor HER4; AltName: Full=p180erbB4; Contains: RecName: Full=ERBB4 intracellular domain; Short=4ICD; Short=E4ICD; AltName: Full=s80HER4; Flags: Precursor;
FUNCTION: Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactaction. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.
CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
ENZYME REGULATION: Binding of a cognate ligand leads to dimerization and activation by autophosphorylation on tyrosine residues. In vitro kinase activity is increased by Mg(2+). Inhibited by PD153035, lapatinib, gefitinib (iressa, ZD1839), AG1478 and BIBX1382BS.
SUBUNIT: Monomer in the absence of bound ligand. Homodimer or heterodimer with another ERBB family member upon ligand binding, thus forming heterotetramers. Interacts with EGFR and ERBB2. Interacts with CBFA2T3 (By similarity). Interacts with DLG2 (via its PDZ domain), DLG3 (via its PDZ domain), DLG4 (via its PDZ domain) and SNTB2 (via its PDZ domain). Interacts with MUC1. Interacts (via its PPxy motifs) with WWOX. Interacts (via the PPxY motif 3 of isoform JM-A CYT-2) with YAP1 (via the WW domain 1 of isoform 1). Interacts (isoform JM-A CYT-1 and isoform JM-B CYT-1) with WWP1. Interacts (via its intracellular domain) with TRIM28. Interacts (via the intracellular domains of both CYT-1 and CYT-2 isoforms) with KAP1; the interaction does not phosphorylate KAP1 but represses ERBB4-mediated transcriptional activity. Interacts with PRPU, DDX23, MATR3, RBM15, ILF3, KAP1, U5S1, U2SURP, ITCH, HNRPU, AP2A1, NULC, LEO1, WWP2, IGHG1, HXK1, GRB7 AND ARS2. Interacts (phosphorylated isoform JM-A CYT-1 and isoform JM-B CYT- 1) with PIK3R1. Interacts with SHC1. Interacts with GRB2. Interacts (soluble intracellular domain) with STAT5A. Interacts (soluble intracellular domain) with BCL2. Interacts (phosphorylated) with STAT1.
INTERACTION: P78352:DLG4; NbExp=6; IntAct=EBI-80371, EBI-80389; P00533:EGFR; NbExp=2; IntAct=EBI-80371, EBI-297353; P04626:ERBB2; NbExp=2; IntAct=EBI-80371, EBI-641062; P21860:ERBB3; NbExp=4; IntAct=EBI-80371, EBI-720706;
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Note=In response to NRG1 treatment, the activated receptor is internalized.
SUBCELLULAR LOCATION: ERBB4 intracellular domain: Nucleus. Mitochondrion. Note=Following proteolytical processing E4ICD (E4ICD1 or E4ICD2 generated from the respective isoforms) is translocated to the nucleus. Significantly more E4ICD2 than E4ICD1 is found in the nucleus. E4ICD2 colocalizes with YAP1 in the nucleus.
TISSUE SPECIFICITY: Expressed at highest levels in brain, heart, kidney, in addition to skeletal muscle, parathyroid, cerebellum, pituitary, spleen, testis and breast. Lower levels in thymus, lung, salivary gland, and pancreas. Isoform JM-A CYT-1 and isoform JM-B CYT-1 are expressed in cerebellum, but only the isoform JM-B is expressed in the heart.
PTM: Isoform JM-A CYT-1 and isoform JM-A CYT-2 are processed by ADAM17. Proteolytic processing in response to ligand or 12-O- tetradecanoylphorbol-13-acetate stimulation results in the production of 120 kDa soluble receptor forms and intermediate membrane-anchored 80 kDa fragments (m80HER4), which are further processed by a presenilin-dependent gamma-secretase to release a cytoplasmic intracellular domain (E4ICD; E4ICD1/s80Cyt1 or E4ICD2/s80Cyt2, depending on the isoform). Membrane-anchored 80 kDa fragments of the processed isoform JM-A CYT-1 are more readily degraded by the proteasome than fragments of isoform JM-A CYT-2, suggesting a prevalence of E4ICD2 over E4ICD1. Isoform JM-B CYT-1 and isoform JM-B CYT-2 lack the ADAM17 cleavage site and are not processed by ADAM17, precluding further processing by gamma- secretase.
PTM: Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Ligands trigger phosphorylation at specific tyrosine residues, thereby creating binding sites for scaffold proteins and effectors. Constitutively phosphorylated at a basal level when overexpressed in heterologous systems; ligand binding leads to increased phosphorylation. Phosphorylation at Tyr-1035 is important for interaction with STAT1. Phosphorylation at Tyr-1056 is important for interaction with PIK3R1. Phosphorylation at Tyr- 1242 is important for interaction with SHC1. Phosphorylation at Tyr-1188 may also contribute to the interaction with SHC1. Isoform JM-A CYT-2 is constitutively phosphorylated on tyrosine residues in a ligand-independent manner. E4ICD2 but not E4ICD1 is phosphorylated on tyrosine residues.
PTM: Ubiquitinated. During mitosis, the ERBB4 intracellular domain is ubiquitinated by the APC/C complex and targeted to proteasomal degradation. Isoform JM-A CYT-1 and isoform JM-B CYT-1 are ubiquitinated by WWP1. The ERBB4 intracellular domain (E4ICD1) is ubiquitinated, and this involves NEDD4.
SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
SIMILARITY: Contains 1 protein kinase domain.
CAUTION: Conflicting reports about the role of ERBB4 in mediating apoptosis, differentiation, or tumor cell proliferation may be explained by the opposite functions of the different isoforms and their intracellular fragments, and by the formation of heterodimers with other EGF receptor family members (PubMed:18454307 and PubMed:21811097). Thus, heterodimer formation of a kinase-dead ERBB4 mutant with ERBB2 is sufficient for the activation of AKT1, MAPK1/ERK2 and MAPK3/ERK1 (PubMed:19098003).

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: ERBB4
Diseases sorted by gene-association score: amyotrophic lateral sclerosis 19* (1235), erbb4-related amyotrophic lateral sclerosis* (500), amyotrophic lateral sclerosis 1* (71), adenocarcinoma (20), childhood medulloblastoma (16), vaginal carcinosarcoma (15), vaginal adenosarcoma (15), papillary hidradenoma (10), paget disease, extramammary (10), medulloblastoma (9), warthin tumor (7), left ventricular outflow tract obstruction (6), breast cancer (6), parotid gland cancer (6), early myoclonic encephalopathy (6), acneiform dermatitis (6), lateral sclerosis (5), phencyclidine abuse (5), trichorhinophalangeal syndrome, type i (4), squamous cell carcinoma (4), hallermann-streiff syndrome (4), lung cancer (3), schizophrenia (2), ovarian cancer, somatic (2), colorectal cancer (2), pilocytic astrocytoma (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 5.09 RPKM in Brain - Anterior cingulate cortex (BA24)
Total median expression: 61.10 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -107.00272-0.393 Picture PostScript Text
3' UTR -1873.107898-0.237 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000494 - EGF_rcpt_L
IPR006211 - Furin-like_Cys-rich_dom
IPR006212 - Furin_repeat
IPR009030 - Growth_fac_rcpt
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR001245 - Ser-Thr/Tyr_kinase_cat_dom
IPR008266 - Tyr_kinase_AS
IPR020635 - Tyr_kinase_cat_dom
IPR016245 - Tyr_kinase_EGF/ERB/XmrK_rcpt

Pfam Domains:
PF00757 - Furin-like cysteine rich region
PF07714 - Protein tyrosine kinase
PF01030 - Receptor L domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2AHX - X-ray MuPIT 2L2T - NMR MuPIT 2LCX - NMR MuPIT 2R4B - X-ray MuPIT 3BBT - X-ray MuPIT 3BBW - X-ray MuPIT 3BCE - X-ray MuPIT 3U2P - X-ray MuPIT 3U7U - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q15303
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGD  WormBase 
Protein SequenceProtein Sequence  Protein Sequence 
AlignmentAlignment  Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0005154 epidermal growth factor receptor binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0042803 protein homodimerization activity
GO:0044212 transcription regulatory region DNA binding
GO:0046934 phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Biological Process:
GO:0000165 MAPK cascade
GO:0001755 neural crest cell migration
GO:0001934 positive regulation of protein phosphorylation
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0007165 signal transduction
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007275 multicellular organism development
GO:0007399 nervous system development
GO:0007507 heart development
GO:0007595 lactation
GO:0008283 cell proliferation
GO:0008284 positive regulation of cell proliferation
GO:0008285 negative regulation of cell proliferation
GO:0009880 embryonic pattern specification
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling
GO:0016310 phosphorylation
GO:0016477 cell migration
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0021551 central nervous system morphogenesis
GO:0021889 olfactory bulb interneuron differentiation
GO:0030334 regulation of cell migration
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0038128 ERBB2 signaling pathway
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity
GO:0043653 mitochondrial fragmentation involved in apoptotic process
GO:0045165 cell fate commitment
GO:0045893 positive regulation of transcription, DNA-templated
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046777 protein autophosphorylation
GO:0046854 phosphatidylinositol phosphorylation
GO:0051897 positive regulation of protein kinase B signaling
GO:0060045 positive regulation of cardiac muscle cell proliferation
GO:0060644 mammary gland epithelial cell differentiation
GO:0060749 mammary gland alveolus development
GO:0061026 cardiac muscle tissue regeneration
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0071364 cellular response to epidermal growth factor stimulus
GO:2000010 positive regulation of protein localization to cell surface
GO:2000145 regulation of cell motility
GO:2001223 negative regulation of neuron migration

Cellular Component:
GO:0005576 extracellular region
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016323 basolateral plasma membrane
GO:0043235 receptor complex


-  Descriptions from all associated GenBank mRNAs
  FW403756 - NUCLEIC ACID COMPOUNDS FOR INHIBITING ERBB FAMILY GENE EXPRESSION AND USES THEREOFF.
L07868 - Homo sapiens receptor tyrosine kinase (ERBB4) gene, complete cds.
BC143747 - Homo sapiens v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian), mRNA (cDNA clone MGC:177278 IMAGE:9052261), complete cds.
BC143749 - Homo sapiens v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian), mRNA (cDNA clone MGC:177280 IMAGE:9052263), complete cds.
BC112199 - Homo sapiens v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian), mRNA (cDNA clone MGC:138404 IMAGE:8327667), complete cds.
BC143741 - Homo sapiens v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian), mRNA (cDNA clone MGC:177272 IMAGE:9052255), complete cds.
AK308606 - Homo sapiens cDNA, FLJ98647.
KT281867 - Homo sapiens ERBB4 transcript variant I20DEL (ERBB4) mRNA, complete cds, alternatively spliced.
KT310076 - Homo sapiens ERBB4 transcript variant I12DEL (ERBB4) mRNA, complete cds, alternatively spliced.
AB209697 - Homo sapiens mRNA for v-erb-a erythroblastic leukemia viral oncogene homolog 4 variant protein.
AF007153 - Homo sapiens clone 23736 mRNA sequence.
AK126298 - Homo sapiens cDNA FLJ44318 fis, clone TRACH3000780.
CR627023 - Homo sapiens mRNA; cDNA DKFZp686G05120 (from clone DKFZp686G05120).
JD036498 - Sequence 17522 from Patent EP1572962.
JD330366 - Sequence 311390 from Patent EP1572962.
JD511741 - Sequence 492765 from Patent EP1572962.
JD435358 - Sequence 416382 from Patent EP1572962.
JD300316 - Sequence 281340 from Patent EP1572962.
JD550089 - Sequence 531113 from Patent EP1572962.
JD085681 - Sequence 66705 from Patent EP1572962.
JD171541 - Sequence 152565 from Patent EP1572962.
JD183162 - Sequence 164186 from Patent EP1572962.
JD290364 - Sequence 271388 from Patent EP1572962.
JD326805 - Sequence 307829 from Patent EP1572962.
JD176071 - Sequence 157095 from Patent EP1572962.
JD075526 - Sequence 56550 from Patent EP1572962.
JD384919 - Sequence 365943 from Patent EP1572962.
JD496581 - Sequence 477605 from Patent EP1572962.
JD222544 - Sequence 203568 from Patent EP1572962.
JD540291 - Sequence 521315 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04012 - ErbB signaling pathway
hsa04020 - Calcium signaling pathway
hsa04144 - Endocytosis

BioCarta from NCI Cancer Genome Anatomy Project
h_erbB4pathway - g-Secretase mediated ErbB4 Signaling Pathway
h_her2Pathway - Role of ERBB2 in Signal Transduction and Oncology

Reactome (by CSHL, EBI, and GO)

Protein Q15303 (Reactome details) participates in the following event(s):

R-HSA-1250220 Homodimerization of ERBB4
R-HSA-1977958 ERBB4 forms heterodimers with ERBB3
R-HSA-1977959 ERBB4 forms heterodimers with EGFR
R-HSA-1236398 ERBB4 binds NRGs or EGF-like ligands
R-HSA-1963589 ERBB2 forms heterodimers with ligand-activated ERBB receptors: EGFR, ERBB3 and ERBB4
R-HSA-1253300 ERBB4 binds WWP1/ITCH ubiquitin ligases
R-HSA-1250353 Binding of p85 subunit of PI3K (PIK3R1) to p-ERBB4cyt1 homodimers
R-HSA-1250315 Trans-autophosphorylation of ERBB4 homodimers
R-HSA-1253282 ERBB4 ubiquitination by WWP1/ITCH
R-HSA-1250372 Recruitment of PI3K subunit p110 (PIK3CA) to PI3K subunit p85 (PIK3R1) bound to p-ERBB4cyt1 homodimers
R-HSA-1250357 SHC1 binds P-ERBB4 isoform dimers
R-HSA-1250346 Binding of PI3K to p-ERBB2:p-ERBB4 CYT-1 heterodimers
R-HSA-1963582 Trans-autophosphorylation of ERBB2 heterodimers
R-HSA-1963586 SRC family kinases phosphorylate ERBB2
R-HSA-1963581 Trans-autophosphorylation of p-Y877-ERBB2 heterodimers
R-HSA-1250380 Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers
R-HSA-1250348 Phosphorylation of SHC1 by ERBB4 homodimers
R-HSA-1306969 GRB2:SOS1 complex binds phosphorylated ERBB4:ERBB2 heterodimers
R-HSA-1250370 Conversion of PIP2 into PIP3 by PI3K bound to p-ERBB4cyt1 homodimers
R-HSA-1306979 PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB4 CYT1
R-HSA-1963563 MATK (CSK homologous kinase) binds phosphorylated ERBB2
R-HSA-1963578 SHC1 binds phosphorylated ERBB2 heterodimers
R-HSA-6785636 Phosphorylated ERBB2 heterodimers bind MEMO1
R-HSA-8847995 Activated ERBB2 binds PTK6 (BRK)
R-HSA-8863804 PTPN12 dephosphorylates ERBB2 on tyrosine Y1248
R-HSA-8848005 ERBB2 promotes PTK6 autophosphorylation
R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity
R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3
R-HSA-1250383 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4
R-HSA-1306972 RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers
R-HSA-1250195 SHC1 phosphorylation by ERBB2 heterodimers
R-HSA-1250486 Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 heterodimers
R-HSA-6785648 MEMO1 binds RHOA:GTP:DIAPH1
R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange
R-HSA-1250463 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-SHC1:Phosphorylated ERBB2 heterodimers
R-HSA-1236394 Signaling by ERBB4
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-1227986 Signaling by ERBB2
R-HSA-1253288 Downregulation of ERBB4 signaling
R-HSA-1250342 PI3K events in ERBB4 signaling
R-HSA-162582 Signal Transduction
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-1963642 PI3K events in ERBB2 signaling
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-8863795 Downregulation of ERBB2 signaling
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-6785631 ERBB2 Regulates Cell Motility
R-HSA-8847993 ERBB2 Activates PTK6 Signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8848021 Signaling by PTK6
R-HSA-2219528 PI3K/AKT Signaling in Cancer
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-199418 Negative regulation of the PI3K/AKT network
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases
R-HSA-5663202 Diseases of signal transduction
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-1643685 Disease
R-HSA-5683057 MAPK family signaling cascades
R-HSA-1236398 ERBB4 binds NRGs or EGF-like ligands
R-HSA-1250220 Homodimerization of ERBB4
R-HSA-1977958 ERBB4 forms heterodimers with ERBB3
R-HSA-1977959 ERBB4 forms heterodimers with EGFR
R-HSA-1963589 ERBB2 forms heterodimers with ligand-activated ERBB receptors: EGFR, ERBB3 and ERBB4
R-HSA-1253300 ERBB4 binds WWP1/ITCH ubiquitin ligases
R-NUL-1251988 Cleavage of P-ERBB4jmA isoforms by Adam17
R-HSA-1251997 Cleavage of ERBB4m80 by gamma-scretase complex
R-HSA-1251992 Cleavage of P-ERBB4jmA isoforms by ADAM17
R-HSA-1252013 Translocation of ERBB4s80 to the nucleus
R-NUL-1253318 ERBB4s80 binds Tab2:Ncor1 complex
R-HSA-1253325 ERBB4s80 binds TAB2:NCOR1 complex
R-HSA-1253343 WWOX binds ERBB4s80
R-HSA-1254251 ERBB4s80 binds YAP1
R-HSA-1254291 ERBB4s80 binds STAT5A
R-HSA-1254376 Translocation of cytosolic ERBB4s80 to mitochondrial matrix
R-HSA-1254386 ERBB4s80 forms a complex with estrogen receptor ESR1
R-HSA-1250315 Trans-autophosphorylation of ERBB4 homodimers
R-HSA-1253282 ERBB4 ubiquitination by WWP1/ITCH
R-HSA-1250357 SHC1 binds P-ERBB4 isoform dimers
R-NUL-1253330 ERBB4:Tab2:Ncor1 complex translocates to the nucleus
R-HSA-1253319 ERBB4s80:TAB2:NCOR1 complex translocates to the nucleus
R-HSA-1254248 Translocation of ERBB4s80:YAP1 complex to the nucleus
R-HSA-1254285 ERBB4s80:STAT5A complex translocates to the nucleus
R-HSA-8954182 ERBB4s80:TAB2:NCOR1 complex binds S100B gene promoter
R-HSA-8954185 ERBB4s80:TAB2:NCOR1 complex binds GFAP gene promoter
R-HSA-8954224 ERBB4s80:STAT5A binds CSN2 gene promoter
R-HSA-8954207 ERBB4s80:ESR1 binds CXCL12 gene promoter
R-HSA-8954208 ERBB4s80:ESR1 binds PGR gene promoter
R-HSA-1963582 Trans-autophosphorylation of ERBB2 heterodimers
R-HSA-1963586 SRC family kinases phosphorylate ERBB2
R-HSA-1963581 Trans-autophosphorylation of p-Y877-ERBB2 heterodimers
R-HSA-1250380 Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers
R-HSA-1250348 Phosphorylation of SHC1 by ERBB4 homodimers
R-HSA-1306969 GRB2:SOS1 complex binds phosphorylated ERBB4:ERBB2 heterodimers
R-HSA-1963563 MATK (CSK homologous kinase) binds phosphorylated ERBB2
R-HSA-1963578 SHC1 binds phosphorylated ERBB2 heterodimers
R-HSA-6785636 Phosphorylated ERBB2 heterodimers bind MEMO1
R-HSA-8847995 Activated ERBB2 binds PTK6 (BRK)
R-HSA-8863804 PTPN12 dephosphorylates ERBB2 on tyrosine Y1248
R-HSA-8848005 ERBB2 promotes PTK6 autophosphorylation
R-HSA-1250383 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4
R-HSA-1306972 RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers
R-HSA-1250195 SHC1 phosphorylation by ERBB2 heterodimers
R-HSA-1250486 Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 heterodimers
R-HSA-6785648 MEMO1 binds RHOA:GTP:DIAPH1
R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange
R-HSA-1250463 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-SHC1:Phosphorylated ERBB2 heterodimers
R-HSA-1236394 Signaling by ERBB4
R-HSA-1227986 Signaling by ERBB2
R-HSA-1253288 Downregulation of ERBB4 signaling
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-9018519 Estrogen-dependent gene expression
R-HSA-162582 Signal Transduction
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-8939211 ESR-mediated signaling
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-9006931 Signaling by Nuclear Receptors
R-HSA-8863795 Downregulation of ERBB2 signaling
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-6785631 ERBB2 Regulates Cell Motility
R-HSA-8847993 ERBB2 Activates PTK6 Signaling
R-HSA-8848021 Signaling by PTK6
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-5683057 MAPK family signaling cascades
R-HSA-1973956 NEDD4 binds ERBB4jmAcyt1s80 dimer
R-HSA-1250220 Homodimerization of ERBB4
R-HSA-1977958 ERBB4 forms heterodimers with ERBB3
R-HSA-1977959 ERBB4 forms heterodimers with EGFR
R-HSA-1236398 ERBB4 binds NRGs or EGF-like ligands
R-NUL-1251988 Cleavage of P-ERBB4jmA isoforms by Adam17
R-HSA-1977296 NEDD4 ubiquitinates ERBB4jmAcyt1s80 dimer
R-HSA-1252013 Translocation of ERBB4s80 to the nucleus
R-NUL-1253318 ERBB4s80 binds Tab2:Ncor1 complex
R-HSA-1253325 ERBB4s80 binds TAB2:NCOR1 complex
R-HSA-1253343 WWOX binds ERBB4s80
R-HSA-1254251 ERBB4s80 binds YAP1
R-HSA-1254291 ERBB4s80 binds STAT5A
R-HSA-1254376 Translocation of cytosolic ERBB4s80 to mitochondrial matrix
R-HSA-1251997 Cleavage of ERBB4m80 by gamma-scretase complex
R-HSA-1251992 Cleavage of P-ERBB4jmA isoforms by ADAM17
R-HSA-1254386 ERBB4s80 forms a complex with estrogen receptor ESR1
R-HSA-1963589 ERBB2 forms heterodimers with ligand-activated ERBB receptors: EGFR, ERBB3 and ERBB4
R-HSA-1253300 ERBB4 binds WWP1/ITCH ubiquitin ligases
R-HSA-1250353 Binding of p85 subunit of PI3K (PIK3R1) to p-ERBB4cyt1 homodimers
R-NUL-1253330 ERBB4:Tab2:Ncor1 complex translocates to the nucleus
R-HSA-1253319 ERBB4s80:TAB2:NCOR1 complex translocates to the nucleus
R-HSA-1254248 Translocation of ERBB4s80:YAP1 complex to the nucleus
R-HSA-1254285 ERBB4s80:STAT5A complex translocates to the nucleus
R-HSA-8954182 ERBB4s80:TAB2:NCOR1 complex binds S100B gene promoter
R-HSA-8954185 ERBB4s80:TAB2:NCOR1 complex binds GFAP gene promoter
R-HSA-8954224 ERBB4s80:STAT5A binds CSN2 gene promoter
R-HSA-8954207 ERBB4s80:ESR1 binds CXCL12 gene promoter
R-HSA-8954208 ERBB4s80:ESR1 binds PGR gene promoter
R-HSA-1250315 Trans-autophosphorylation of ERBB4 homodimers
R-HSA-1253282 ERBB4 ubiquitination by WWP1/ITCH
R-HSA-1250372 Recruitment of PI3K subunit p110 (PIK3CA) to PI3K subunit p85 (PIK3R1) bound to p-ERBB4cyt1 homodimers
R-HSA-1250357 SHC1 binds P-ERBB4 isoform dimers
R-HSA-1250346 Binding of PI3K to p-ERBB2:p-ERBB4 CYT-1 heterodimers
R-HSA-1963582 Trans-autophosphorylation of ERBB2 heterodimers
R-HSA-1963586 SRC family kinases phosphorylate ERBB2
R-HSA-1963581 Trans-autophosphorylation of p-Y877-ERBB2 heterodimers
R-HSA-1250380 Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers
R-HSA-1250348 Phosphorylation of SHC1 by ERBB4 homodimers
R-HSA-1306969 GRB2:SOS1 complex binds phosphorylated ERBB4:ERBB2 heterodimers
R-HSA-1250370 Conversion of PIP2 into PIP3 by PI3K bound to p-ERBB4cyt1 homodimers
R-HSA-1306979 PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB4 CYT1
R-HSA-1963563 MATK (CSK homologous kinase) binds phosphorylated ERBB2
R-HSA-1963578 SHC1 binds phosphorylated ERBB2 heterodimers
R-HSA-6785636 Phosphorylated ERBB2 heterodimers bind MEMO1
R-HSA-8847995 Activated ERBB2 binds PTK6 (BRK)
R-HSA-8863804 PTPN12 dephosphorylates ERBB2 on tyrosine Y1248
R-HSA-8848005 ERBB2 promotes PTK6 autophosphorylation
R-HSA-2400009 PI3K inhibitors block PI3K catalytic activity
R-HSA-2316434 PI3K phosphorylates PIP2 to PIP3
R-HSA-1250383 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4
R-HSA-1306972 RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers
R-HSA-1250195 SHC1 phosphorylation by ERBB2 heterodimers
R-HSA-1250486 Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 heterodimers
R-HSA-6785648 MEMO1 binds RHOA:GTP:DIAPH1
R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange
R-HSA-1250463 RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-SHC1:Phosphorylated ERBB2 heterodimers
R-HSA-1253288 Downregulation of ERBB4 signaling
R-HSA-1236394 Signaling by ERBB4
R-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-9018519 Estrogen-dependent gene expression
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-1227986 Signaling by ERBB2
R-HSA-1250342 PI3K events in ERBB4 signaling
R-HSA-8939211 ESR-mediated signaling
R-HSA-162582 Signal Transduction
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-1963642 PI3K events in ERBB2 signaling
R-HSA-9006931 Signaling by Nuclear Receptors
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-8863795 Downregulation of ERBB2 signaling
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-6785631 ERBB2 Regulates Cell Motility
R-HSA-8847993 ERBB2 Activates PTK6 Signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8848021 Signaling by PTK6
R-HSA-2219528 PI3K/AKT Signaling in Cancer
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-199418 Negative regulation of the PI3K/AKT network
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases
R-HSA-5663202 Diseases of signal transduction
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-1643685 Disease
R-HSA-5683057 MAPK family signaling cascades

-  Other Names for This Gene
  Alternate Gene Symbols: B7ZLD7, B7ZLE2, B7ZLE3, ENST00000342788.1, ENST00000342788.2, ENST00000342788.3, ENST00000342788.4, ENST00000342788.5, ENST00000342788.6, ENST00000342788.7, ENST00000342788.8, ERBB4_HUMAN, HER4, NM_005235, Q15303, Q2M1W1, Q59EW4, uc002veg.1, uc002veg.2, uc002veg.3
UCSC ID: ENST00000342788.9
RefSeq Accession: NM_005235
Protein: Q15303 (aka ERBB4_HUMAN)
CCDS: CCDS2394.1, CCDS42811.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ERBB4:
als-overview (Amyotrophic Lateral Sclerosis Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.