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Protein

Receptor tyrosine-protein kinase erbB-4

Gene

ERBB4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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 lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.22 Publications

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).1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Binding of a cognate ligand leads to dimerization and activation by autophosphorylation on tyrosine residues. In vitro kinase activity is increased by Mg2+. Inhibited by PD153035, lapatinib, gefitinib (iressa, ZD1839), AG1478 and BIBX1382BS.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei751ATPPROSITE-ProRule annotation1
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei843Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi724 – 732ATPPROSITE-ProRule annotation9
Nucleotide bindingi797 – 799ATPPROSITE-ProRule annotation3
Nucleotide bindingi843 – 848ATPPROSITE-ProRule annotation6

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActivator, Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processApoptosis, Lactation, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.10.1 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-1227986 Signaling by ERBB2
R-HSA-1236394 Signaling by ERBB4
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1250342 PI3K events in ERBB4 signaling
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-1253288 Downregulation of ERBB4 signaling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-1963642 PI3K events in ERBB2 signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6785631 ERBB2 Regulates Cell Motility
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8847993 ERBB2 Activates PTK6 Signaling
R-HSA-8863795 Downregulation of ERBB2 signaling
R-HSA-9018519 Estrogen-dependent gene expression

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
Q15303

SIGNOR Signaling Network Open Resource

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SIGNORi
Q15303

Protein family/group databases

Transport Classification Database

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TCDBi
1.A.87.2.6 the mechanosensitive calcium channel (mca) family

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Receptor tyrosine-protein kinase erbB-4 (EC:2.7.10.1)
Alternative name(s):
Proto-oncogene-like protein c-ErbB-4
Tyrosine kinase-type cell surface receptor HER4
p180erbB4
Cleaved into the following chain:
ERBB4 intracellular domain
Short name:
4ICD
Short name:
E4ICD
Alternative name(s):
s80HER4
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:ERBB4
Synonyms:HER4
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 2

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000178568.13

Human Gene Nomenclature Database

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HGNCi
HGNC:3432 ERBB4

Online Mendelian Inheritance in Man (OMIM)

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MIMi
600543 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_Q15303

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini26 – 651ExtracellularSequence analysisAdd BLAST626
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei652 – 675HelicalSequence analysisAdd BLAST24
Topological domaini676 – 1308CytoplasmicSequence analysisAdd BLAST633

Keywords - Cellular componenti

Cell membrane, Membrane, Mitochondrion, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Amyotrophic lateral sclerosis 19 (ALS19)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.
See also OMIM:615515
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_070810927R → Q in ALS19; reduces autophosphorylation upon NRG1 stimulation. 1 PublicationCorresponds to variant dbSNP:rs397514262EnsemblClinVar.1
Natural variantiVAR_0708111275R → W in ALS19; reduces autophosphorylation upon NRG1 stimulation. 1 PublicationCorresponds to variant dbSNP:rs397514263EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi646Q → C: Constitutively activated kinase. 1 Publication1
Mutagenesisi675V → A: Abolishes proteolytic processing and nuclear localization. 2 Publications1
Mutagenesisi681 – 684KKKR → EIMG: Abolishes nuclear localization of the ERBB4 intracellular domain. 1 Publication4
Mutagenesisi710L → N: Strongly reduced autophosphorylation. 1 Publication1
Mutagenesisi721V → I: No effect on kinase activity. 1 Publication1
Mutagenesisi751K → R: Abolishes kinase activity. Abolishes phosphorylation, proteolytic processing and nuclear localization. 3 Publications1
Mutagenesisi766M → R: Strongly reduced autophosphorylation. 1 Publication1
Mutagenesisi773A → S: No effect on kinase activity. 1 Publication1
Mutagenesisi782R → Q: No effect on kinase activity. 1 Publication1
Mutagenesisi810E → K: No effect on kinase activity. 1 Publication1
Mutagenesisi843D → N: Loss of kinase activity. 1 Publication1
Mutagenesisi854P → Q: No effect on kinase activity. 1 Publication1
Mutagenesisi861D → Y: Loss of kinase activity. 1 Publication1
Mutagenesisi864L → R: Strongly reduced autophosphorylation. 1 Publication1
Mutagenesisi872E → K: No effect on kinase activity. 1 Publication1
Mutagenesisi926T → M: No effect on kinase activity. 1 Publication1
Mutagenesisi947I → R: Constitutively autophosphorylated. 1 Publication1
Mutagenesisi992R → A: Abolishes APC/C-mediated degradation; when associated with A-995 and A-1000. 1 Publication1
Mutagenesisi995L → A: Abolishes APC/C-mediated degradation; when associated with A-992 and A-1000. 1 Publication1
Mutagenesisi1000D → A: Abolishes APC/C-mediated degradation; when associated with A-992 and A-995. 1 Publication1
Mutagenesisi1035Y → A: No effect on interaction with WWOX. Abolishes interaction with WWOX; when associated with A-1301. 1 Publication1
Mutagenesisi1056Y → A: Abolishes interaction with NEDD4 and impairs ubiquitination. Promotes nuclear translocation of ERBB4 intracellular domain E4ICD1. 1 Publication1
Mutagenesisi1056Y → F: Abolishes interaction with WWP1; when associated with F-1301. 1 Publication1
Mutagenesisi1301Y → A: Abolishes interaction with NEDD4 and impairs ubiquitination. 3 Publications1
Mutagenesisi1301Y → A: No effect on interaction with WWOX. Abolishes interaction with WWOX; when associated with A-1035. Loss of interaction with YAP1 and stimulation of transcription. 3 Publications1
Mutagenesisi1301Y → F: Abolishes interaction with WWP1; when associated with F-1056. 3 Publications1

Keywords - Diseasei

Amyotrophic lateral sclerosis, Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNET

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DisGeNETi
2066

MalaCards human disease database

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MalaCardsi
ERBB4
MIMi615515 phenotype

Open Targets

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OpenTargetsi
ENSG00000178568

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
803 Amyotrophic lateral sclerosis

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA27847

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL3009

Drug and drug target database

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DrugBanki
DB08916 Afatinib

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
1799

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
ERBB4

Domain mapping of disease mutations (DMDM)

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DMDMi
3913590

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 25Sequence analysisAdd BLAST25
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001667426 – 1308Receptor tyrosine-protein kinase erbB-4Add BLAST1283
ChainiPRO_0000396797676 – 1308ERBB4 intracellular domainBy similarityAdd BLAST633

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi29 ↔ 561 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi138N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi156 ↔ 1861 Publication
Glycosylationi174N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi181N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi189 ↔ 1971 Publication
Disulfide bondi193 ↔ 2051 Publication
Disulfide bondi213 ↔ 2211 Publication
Disulfide bondi217 ↔ 2291 Publication
Disulfide bondi230 ↔ 2381 Publication
Disulfide bondi234 ↔ 2461 Publication
Disulfide bondi249 ↔ 2581 Publication
Glycosylationi253N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi262 ↔ 2891 Publication
Disulfide bondi293 ↔ 3041 Publication
Disulfide bondi308 ↔ 3231 Publication
Disulfide bondi326 ↔ 3301 Publication
Glycosylationi358N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi410N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi473N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi495N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi503 ↔ 5121 Publication
Disulfide bondi507 ↔ 5201 Publication
Disulfide bondi523 ↔ 5321 Publication
Disulfide bondi536 ↔ 5521 Publication
Glycosylationi548N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi555 ↔ 5691 Publication
Disulfide bondi559 ↔ 5771 Publication
Glycosylationi576N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi580 ↔ 5891 Publication
Disulfide bondi593 ↔ 6141 Publication
Disulfide bondi617 ↔ 6251 Publication
Glycosylationi620N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi621 ↔ 6331 Publication
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei875Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1035Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1056Phosphotyrosine; by autocatalysis3 Publications1
Modified residuei1150Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1162Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1188Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei1202Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1242Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei1258Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1284Phosphotyrosine; by autocatalysis1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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.6 Publications
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.7 Publications
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 NEDD4.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q15303

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q15303

MaxQB - The MaxQuant DataBase

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MaxQBi
Q15303

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q15303

PeptideAtlas

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PeptideAtlasi
Q15303

PRoteomics IDEntifications database

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PRIDEi
Q15303

ProteomicsDB human proteome resource

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ProteomicsDBi
60520
60521 [Q15303-2]
60522 [Q15303-3]
60523 [Q15303-4]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q15303

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q15303

Miscellaneous databases

CutDB - Proteolytic event database

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PMAP-CutDBi
Q15303

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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.3 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000178568 Expressed in 168 organ(s), highest expression level in oviduct epithelium

CleanEx database of gene expression profiles

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CleanExi
HS_ERBB4

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q15303 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q15303 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB000276
CAB025522
HPA012016

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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, HNRNPU, 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.By similarity29 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
108378, 78 interactors

Database of interacting proteins

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DIPi
DIP-29650N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
Q15303

Protein interaction database and analysis system

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IntActi
Q15303, 30 interactors

Molecular INTeraction database

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MINTi
Q15303

STRING: functional protein association networks

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STRINGi
9606.ENSP00000342235

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q15303

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11308
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AHXX-ray2.40A/B26-641[»]
2L2TNMR-A/B642-685[»]
2LCXNMR-A/B642-685[»]
2R4BX-ray2.40A/B690-999[»]
3BBTX-ray2.80B/D702-1029[»]
3BBWX-ray4.00A/B702-1029[»]
3BCEX-ray2.50A/B/C702-1029[»]
3U2PX-ray2.57A26-522[»]
3U7UX-ray3.03A/B/C/D/E/F26-640[»]
3U9UX-ray3.42E/F26-650[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
Q15303

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q15303

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
Q15303

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini718 – 985Protein kinasePROSITE-ProRule annotationAdd BLAST268

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi676 – 684Nuclear localization signal9
Motifi1032 – 1035PPxY motif 14
Motifi1053 – 1056PPxY motif 24
Motifi1298 – 1301PPxY motif 34
Motifi1306 – 1308PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi186 – 334Cys-richAdd BLAST149
Compositional biasi496 – 633Cys-richAdd BLAST138

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG1025 Eukaryota
ENOG410XNSR LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000154695

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000230982

The HOVERGEN Database of Homologous Vertebrate Genes

More...
HOVERGENi
HBG000490

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q15303

KEGG Orthology (KO)

More...
KOi
K05085

Identification of Orthologs from Complete Genome Data

More...
OMAi
KQNGHIR

Database of Orthologous Groups

More...
OrthoDBi
81952at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q15303

TreeFam database of animal gene trees

More...
TreeFami
TF106002

Family and domain databases

Conserved Domains Database

More...
CDDi
cd00064 FU, 3 hits

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.80.20.20, 2 hits

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR006211 Furin-like_Cys-rich_dom
IPR006212 Furin_repeat
IPR032778 GF_recep_IV
IPR009030 Growth_fac_rcpt_cys_sf
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR000494 Rcpt_L-dom
IPR036941 Rcpt_L-dom_sf
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016245 Tyr_kinase_EGF/ERB/XmrK_rcpt

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00757 Furin-like, 1 hit
PF14843 GF_recep_IV, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF01030 Recep_L_domain, 2 hits

PIRSF; a whole-protein classification database

More...
PIRSFi
PIRSF000619 TyrPK_EGF-R, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR00109 TYRKINASE

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00261 FU, 5 hits
SM00219 TyrKc, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 2 hits

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (4+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform JM-A CYT-1 (identifier: Q15303-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MKPATGLWVW VSLLVAAGTV QPSDSQSVCA GTENKLSSLS DLEQQYRALR
60 70 80 90 100
KYYENCEVVM GNLEITSIEH NRDLSFLRSV REVTGYVLVA LNQFRYLPLE
110 120 130 140 150
NLRIIRGTKL YEDRYALAIF LNYRKDGNFG LQELGLKNLT EILNGGVYVD
160 170 180 190 200
QNKFLCYADT IHWQDIVRNP WPSNLTLVST NGSSGCGRCH KSCTGRCWGP
210 220 230 240 250
TENHCQTLTR TVCAEQCDGR CYGPYVSDCC HRECAGGCSG PKDTDCFACM
260 270 280 290 300
NFNDSGACVT QCPQTFVYNP TTFQLEHNFN AKYTYGAFCV KKCPHNFVVD
310 320 330 340 350
SSSCVRACPS SKMEVEENGI KMCKPCTDIC PKACDGIGTG SLMSAQTVDS
360 370 380 390 400
SNIDKFINCT KINGNLIFLV TGIHGDPYNA IEAIDPEKLN VFRTVREITG
410 420 430 440 450
FLNIQSWPPN MTDFSVFSNL VTIGGRVLYS GLSLLILKQQ GITSLQFQSL
460 470 480 490 500
KEISAGNIYI TDNSNLCYYH TINWTTLFST INQRIVIRDN RKAENCTAEG
510 520 530 540 550
MVCNHLCSSD GCWGPGPDQC LSCRRFSRGR ICIESCNLYD GEFREFENGS
560 570 580 590 600
ICVECDPQCE KMEDGLLTCH GPGPDNCTKC SHFKDGPNCV EKCPDGLQGA
610 620 630 640 650
NSFIFKYADP DRECHPCHPN CTQGCNGPTS HDCIYYPWTG HSTLPQHART
660 670 680 690 700
PLIAAGVIGG LFILVIVGLT FAVYVRRKSI KKKRALRRFL ETELVEPLTP
710 720 730 740 750
SGTAPNQAQL RILKETELKR VKVLGSGAFG TVYKGIWVPE GETVKIPVAI
760 770 780 790 800
KILNETTGPK ANVEFMDEAL IMASMDHPHL VRLLGVCLSP TIQLVTQLMP
810 820 830 840 850
HGCLLEYVHE HKDNIGSQLL LNWCVQIAKG MMYLEERRLV HRDLAARNVL
860 870 880 890 900
VKSPNHVKIT DFGLARLLEG DEKEYNADGG KMPIKWMALE CIHYRKFTHQ
910 920 930 940 950
SDVWSYGVTI WELMTFGGKP YDGIPTREIP DLLEKGERLP QPPICTIDVY
960 970 980 990 1000
MVMVKCWMID ADSRPKFKEL AAEFSRMARD PQRYLVIQGD DRMKLPSPND
1010 1020 1030 1040 1050
SKFFQNLLDE EDLEDMMDAE EYLVPQAFNI PPPIYTSRAR IDSNRSEIGH
1060 1070 1080 1090 1100
SPPPAYTPMS GNQFVYRDGG FAAEQGVSVP YRAPTSTIPE APVAQGATAE
1110 1120 1130 1140 1150
IFDDSCCNGT LRKPVAPHVQ EDSSTQRYSA DPTVFAPERS PRGELDEEGY
1160 1170 1180 1190 1200
MTPMRDKPKQ EYLNPVEENP FVSRRKNGDL QALDNPEYHN ASNGPPKAED
1210 1220 1230 1240 1250
EYVNEPLYLN TFANTLGKAE YLKNNILSMP EKAKKAFDNP DYWNHSLPPR
1260 1270 1280 1290 1300
STLQHPDYLQ EYSTKYFYKQ NGRIRPIVAE NPEYLSEFSL KPGTVLPPPP

YRHRNTVV
Note: Proteolytical processing generates E4ICD1 (s80Cyt1).
Length:1,308
Mass (Da):146,808
Last modified:November 1, 1996 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i5E4AE80985D88761
GO
Isoform JM-B CYT-1 (identifier: Q15303-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     626-648: NGPTSHDCIYYPWTGHSTLPQHA → IGSSIEDCIGLMD

Show »
Length:1,298
Mass (Da):145,578
Checksum:i346C1288AD041961
GO
Isoform JM-A CYT-2 (identifier: Q15303-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1046-1061: Missing.

Note: Proteolytical processing generates E4ICD2 (s80Cyt2).
Show »
Length:1,292
Mass (Da):145,198
Checksum:i60C0DFD446C7FA89
GO
Isoform JM-B CYT-2 (identifier: Q15303-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     626-648: NGPTSHDCIYYPWTGHSTLPQHA → IGSSIEDCIGLMD
     1046-1061: Missing.

Show »
Length:1,282
Mass (Da):143,968
Checksum:i68F27777BC9E2F74
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MSE1A0A0A0MSE1_HUMAN
Receptor protein-tyrosine kinase
ERBB4
1,266Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H3BLT0H3BLT0_HUMAN
Receptor tyrosine-protein kinase er...
ERBB4
731Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E9PDR1E9PDR1_HUMAN
Receptor tyrosine-protein kinase er...
ERBB4
128Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042113140T → I in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042114303S → Y in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_070810927R → Q in ALS19; reduces autophosphorylation upon NRG1 stimulation. 1 PublicationCorresponds to variant dbSNP:rs397514262EnsemblClinVar.1
Natural variantiVAR_0708111275R → W in ALS19; reduces autophosphorylation upon NRG1 stimulation. 1 PublicationCorresponds to variant dbSNP:rs397514263EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting. The information stored in this subsection is used to automatically construct alternative protein sequence(s) for display.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_002895626 – 648NGPTS…LPQHA → IGSSIEDCIGLMD in isoform JM-B CYT-1 and isoform JM-B CYT-2. 2 PublicationsAdd BLAST23
Alternative sequenceiVSP_0221481046 – 1061Missing in isoform JM-A CYT-2 and isoform JM-B CYT-2. 2 PublicationsAdd BLAST16

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
L07868 mRNA Translation: AAB59446.1
BC112199 mRNA Translation: AAI12200.1
BC143741 mRNA Translation: AAI43742.1
BC143747 mRNA Translation: AAI43748.1
BC143749 mRNA Translation: AAI43750.1
AB209697 mRNA Translation: BAD92934.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS2394.1 [Q15303-1]
CCDS42811.1 [Q15303-3]

Protein sequence database of the Protein Information Resource

More...
PIRi
A47253

NCBI Reference Sequences

More...
RefSeqi
NP_001036064.1, NM_001042599.1 [Q15303-3]
NP_005226.1, NM_005235.2 [Q15303-1]
XP_005246433.1, XM_005246376.2 [Q15303-2]
XP_005246434.1, XM_005246377.2 [Q15303-4]

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.390729

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000342788; ENSP00000342235; ENSG00000178568 [Q15303-1]
ENST00000436443; ENSP00000403204; ENSG00000178568 [Q15303-3]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
2066

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:2066

UCSC genome browser

More...
UCSCi
uc002veg.2 human [Q15303-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L07868 mRNA Translation: AAB59446.1
BC112199 mRNA Translation: AAI12200.1
BC143741 mRNA Translation: AAI43742.1
BC143747 mRNA Translation: AAI43748.1
BC143749 mRNA Translation: AAI43750.1
AB209697 mRNA Translation: BAD92934.1
CCDSiCCDS2394.1 [Q15303-1]
CCDS42811.1 [Q15303-3]
PIRiA47253
RefSeqiNP_001036064.1, NM_001042599.1 [Q15303-3]
NP_005226.1, NM_005235.2 [Q15303-1]
XP_005246433.1, XM_005246376.2 [Q15303-2]
XP_005246434.1, XM_005246377.2 [Q15303-4]
UniGeneiHs.390729

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AHXX-ray2.40A/B26-641[»]
2L2TNMR-A/B642-685[»]
2LCXNMR-A/B642-685[»]
2R4BX-ray2.40A/B690-999[»]
3BBTX-ray2.80B/D702-1029[»]
3BBWX-ray4.00A/B702-1029[»]
3BCEX-ray2.50A/B/C702-1029[»]
3U2PX-ray2.57A26-522[»]
3U7UX-ray3.03A/B/C/D/E/F26-640[»]
3U9UX-ray3.42E/F26-650[»]
ProteinModelPortaliQ15303
SMRiQ15303
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108378, 78 interactors
DIPiDIP-29650N
ELMiQ15303
IntActiQ15303, 30 interactors
MINTiQ15303
STRINGi9606.ENSP00000342235

Chemistry databases

BindingDBiQ15303
ChEMBLiCHEMBL3009
DrugBankiDB08916 Afatinib
GuidetoPHARMACOLOGYi1799

Protein family/group databases

TCDBi1.A.87.2.6 the mechanosensitive calcium channel (mca) family

PTM databases

iPTMnetiQ15303
PhosphoSitePlusiQ15303

Polymorphism and mutation databases

BioMutaiERBB4
DMDMi3913590

Proteomic databases

EPDiQ15303
jPOSTiQ15303
MaxQBiQ15303
PaxDbiQ15303
PeptideAtlasiQ15303
PRIDEiQ15303
ProteomicsDBi60520
60521 [Q15303-2]
60522 [Q15303-3]
60523 [Q15303-4]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
2066
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342788; ENSP00000342235; ENSG00000178568 [Q15303-1]
ENST00000436443; ENSP00000403204; ENSG00000178568 [Q15303-3]
GeneIDi2066
KEGGihsa:2066
UCSCiuc002veg.2 human [Q15303-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
2066
DisGeNETi2066
EuPathDBiHostDB:ENSG00000178568.13

GeneCards: human genes, protein and diseases

More...
GeneCardsi
ERBB4
HGNCiHGNC:3432 ERBB4
HPAiCAB000276
CAB025522
HPA012016
MalaCardsiERBB4
MIMi600543 gene
615515 phenotype
neXtProtiNX_Q15303
OpenTargetsiENSG00000178568
Orphaneti803 Amyotrophic lateral sclerosis
PharmGKBiPA27847

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1025 Eukaryota
ENOG410XNSR LUCA
GeneTreeiENSGT00940000154695
HOGENOMiHOG000230982
HOVERGENiHBG000490
InParanoidiQ15303
KOiK05085
OMAiKQNGHIR
OrthoDBi81952at2759
PhylomeDBiQ15303
TreeFamiTF106002

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-1227986 Signaling by ERBB2
R-HSA-1236394 Signaling by ERBB4
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1250342 PI3K events in ERBB4 signaling
R-HSA-1250347 SHC1 events in ERBB4 signaling
R-HSA-1251985 Nuclear signaling by ERBB4
R-HSA-1253288 Downregulation of ERBB4 signaling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1963640 GRB2 events in ERBB2 signaling
R-HSA-1963642 PI3K events in ERBB2 signaling
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6785631 ERBB2 Regulates Cell Motility
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8847993 ERBB2 Activates PTK6 Signaling
R-HSA-8863795 Downregulation of ERBB2 signaling
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiQ15303
SIGNORiQ15303

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

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ChiTaRSi
ERBB4 human
EvolutionaryTraceiQ15303

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
ERBB4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
2066
PMAP-CutDBiQ15303

Protein Ontology

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PROi
PR:Q15303

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
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Gene expression databases

BgeeiENSG00000178568 Expressed in 168 organ(s), highest expression level in oviduct epithelium
CleanExiHS_ERBB4
ExpressionAtlasiQ15303 baseline and differential
GenevisibleiQ15303 HS

Family and domain databases

CDDicd00064 FU, 3 hits
Gene3Di3.80.20.20, 2 hits
InterProiView protein in InterPro
IPR006211 Furin-like_Cys-rich_dom
IPR006212 Furin_repeat
IPR032778 GF_recep_IV
IPR009030 Growth_fac_rcpt_cys_sf
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR000494 Rcpt_L-dom
IPR036941 Rcpt_L-dom_sf
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016245 Tyr_kinase_EGF/ERB/XmrK_rcpt
PfamiView protein in Pfam
PF00757 Furin-like, 1 hit
PF14843 GF_recep_IV, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF01030 Recep_L_domain, 2 hits
PIRSFiPIRSF000619 TyrPK_EGF-R, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00261 FU, 5 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 2 hits
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
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<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiERBB4_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q15303
Secondary accession number(s): B7ZLD7
, B7ZLE2, B7ZLE3, Q2M1W1, Q59EW4
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: January 16, 2019
This is version 213 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
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