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Entry version 245 (05 Jun 2019)
Sequence version 1 (13 Aug 1987)
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Protein

Receptor tyrosine-protein kinase erbB-2

Gene

ERBB2

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

Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.Curated
In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.3 Publications

<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 <a href="http://www.uniprot.org/help/function_section">Function</a> 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

Activated by dimerization. Not activated by EGF, TGF-alpha and amphiregulin. Interaction with PTK6 increases its intrinsic kinase activity.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> 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 sitei753ATPPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> 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 sitei845Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> 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 bindingi726 – 734ATPPROSITE-ProRule annotation9

<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, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processTranscription, 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-1250196 SHC1 events in ERBB2 signaling
R-HSA-1251932 PLCG1 events in ERBB2 signaling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1306955 GRB7 events in ERBB2 signaling
R-HSA-1358803 Downregulation of ERBB2:ERBB3 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-416572 Sema4D induced cell migration and growth-cone collapse
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-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptors

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

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SignaLinki
P04626

SIGNOR Signaling Network Open Resource

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SIGNORi
P04626

Protein family/group databases

MoonDB Database of extreme multifunctional and moonlighting proteins

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MoonDBi
P04626 Predicted

<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-2 (EC:2.7.10.1)
Alternative name(s):
Metastatic lymph node gene 19 protein
Short name:
MLN 19
Proto-oncogene Neu
Proto-oncogene c-ErbB-2
Tyrosine kinase-type cell surface receptor HER2
p185erbB2
CD_antigen: CD340
<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:ERBB2
Synonyms:HER2, MLN19, NEU, NGL
<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 17

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:3430 ERBB2

Online Mendelian Inheritance in Man (OMIM)

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MIMi
164870 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P04626

<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 & Seán O’Donoghue; 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 domaini23 – 652ExtracellularSequence analysisAdd BLAST630
<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>Transmembranei653 – 675HelicalSequence analysisAdd BLAST23
Topological domaini676 – 1255CytoplasmicSequence analysisAdd BLAST580

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, 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

Glioma (GLM)1 Publication
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionGliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes.
Related information in OMIM
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_055435914E → K in GLM; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs28933368Ensembl.1
Ovarian cancer (OC)2 Publications
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionThe term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042099857N → S in OC; somatic mutation; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs28933370Ensembl.1
Lung cancer (LNCR)1 Publication
The gene represented in this entry is involved in disease pathogenesis.
Disease descriptionA common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055432755L → P in LNCR; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs121913469Ensembl.1
Natural variantiVAR_055433774M → MAYVM in LNCR; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_055434779S → SVGS in LNCR; somatic mutation; unknown pathological significance. 1 Publication1
Gastric cancer (GASC)2 Publications
The protein represented in this entry is involved in disease pathogenesis.
Disease descriptionA malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042098776G → S in GASC; somatic mutation; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs28933369Ensembl.1
Chromosomal aberrations involving ERBB2 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to truncated CDK12 protein not in-frame with ERBB2.1 Publication

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>Mutagenesisi317 – 318LH → AA: Reduces dimerization with ERBB3. 1 Publication2
Mutagenesisi611M → A: Prevents synthesis of isoform 2. 1 Publication1
Mutagenesisi687M → A: Prevents synthesis of isoform 3. 1 Publication1
Mutagenesisi706M → A: No effect on isoform production. 1 Publication1
Mutagenesisi712M → A: No effect on isoform production. 1 Publication1

Organism-specific databases

DisGeNET

More...
DisGeNETi
2064

MalaCards human disease database

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MalaCardsi
ERBB2
MIMi137800 phenotype
167000 phenotype
211980 phenotype
613659 phenotype

Open Targets

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OpenTargetsi
ENSG00000141736

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA27844

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL1824

Drug and drug target database

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DrugBanki
DB08916 Afatinib
DB04988 IGN311
DB01259 Lapatinib
DB06366 Pertuzumab
DB00072 Trastuzumab
DB05773 Trastuzumab emtansine
DB05007 XL647

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2019

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
ERBB2

Domain mapping of disease mutations (DMDM)

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DMDMi
119533

<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 – 22Sequence analysisAdd BLAST22
<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_000001666923 – 1255Receptor tyrosine-protein kinase erbB-2Add BLAST1233

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 bondi26 ↔ 53Combined sources
<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>Glycosylationi68N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Glycosylationi124N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi162 ↔ 192Combined sources
<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 residuei182PhosphothreonineCombined sources1
Glycosylationi187N-linked (GlcNAc...) asparagineSequence analysisCombined sources1
Disulfide bondi195 ↔ 204Combined sources
Disulfide bondi199 ↔ 212Combined sources
Disulfide bondi220 ↔ 227Combined sources
Disulfide bondi224 ↔ 235Combined sources
Disulfide bondi236 ↔ 244Combined sources
Disulfide bondi240 ↔ 252Combined sources
Disulfide bondi255 ↔ 264Combined sources
Glycosylationi259N-linked (GlcNAc...) asparagineCombined sources3 Publications1
Disulfide bondi268 ↔ 295Combined sources
Disulfide bondi299 ↔ 311Combined sources
Disulfide bondi315 ↔ 331Combined sources
Disulfide bondi334 ↔ 338Combined sources
Disulfide bondi342 ↔ 367Combined sources
Disulfide bondi475 ↔ 504Combined sources
Disulfide bondi511 ↔ 520Combined sources
Disulfide bondi515 ↔ 528Combined sources
Glycosylationi530N-linked (GlcNAc...) asparagineCombined sources2 Publications1
Disulfide bondi531 ↔ 540Combined sources
Disulfide bondi544 ↔ 560Combined sources
Disulfide bondi563 ↔ 576Combined sources
Disulfide bondi567 ↔ 584Combined sources
Glycosylationi571N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi587 ↔ 596Combined sources
Disulfide bondi600 ↔ 623Combined sources
Disulfide bondi626 ↔ 634Combined sources
Glycosylationi629N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi630 ↔ 642Combined sources
Modified residuei1054PhosphoserineCombined sources1
Modified residuei1078PhosphoserineBy similarity1
Modified residuei1083PhosphoserineCombined sources1
Modified residuei1107PhosphoserineCombined sources1
Modified residuei1112Phosphotyrosine1 Publication1
Modified residuei1139Phosphotyrosine1 Publication1
Modified residuei1151PhosphoserineCombined sources1
Modified residuei1166PhosphothreonineCombined sources1
Modified residuei1196Phosphotyrosine1 Publication1
Modified residuei1248Phosphotyrosine; by autocatalysisCombined sources2 Publications1

<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

Autophosphorylated. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit (Probable). Ligand-binding increases phosphorylation on tyrosine residues (PubMed:27134172). Signaling via SEMA4C promotes phosphorylation at Tyr-1248 (PubMed:17554007). Dephosphorylated by PTPN12 (PubMed:27134172).Curated2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P04626

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P04626

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

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PaxDbi
P04626

PeptideAtlas

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PeptideAtlasi
P04626

PRoteomics IDEntifications database

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PRIDEi
P04626

ProteomicsDB human proteome resource

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ProteomicsDBi
51718
51719 [P04626-2]
51720 [P04626-3]
51721 [P04626-4]

PTM databases

CarbonylDB database of protein carbonylation sites

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CarbonylDBi
P04626

GlyConnect protein glycosylation platform

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GlyConnecti
1710

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P04626

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

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PhosphoSitePlusi
P04626

Miscellaneous databases

CutDB - Proteolytic event database

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PMAP-CutDBi
P04626

<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 in a variety of tumor tissues including primary breast tumors and tumors from small bowel, esophagus, kidney and mouth.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000141736 Expressed in 212 organ(s), highest expression level in esophagus mucosa

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P04626 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P04626 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
CAB000043
CAB020416
CAB062555
HPA001060
HPA001338
HPA001383

<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

Homodimer (PubMed:21454582). Heterodimer with EGFR, ERBB3 and ERBB4 (PubMed:10358079, PubMed:15093539, PubMed:21190959, PubMed:16978839). Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1196 (PubMed:10805725). Interacts with PLXNB1 (PubMed:15210733). Interacts (when phosphorylated on Tyr-1248) with MEMO1 (PubMed:15156151). Interacts with MUC1; the interaction is enhanced by heregulin (HRG) (PubMed:12939402). Interacts (when phosphorylated on Tyr-1139) with GRB7 (via SH2 domain) (PubMed:12975581). Interacts (when phosphorylated on Tyr-1248) with ERBIN (PubMed:12444095). Interacts with KPNB1, RANBP2, EEA1, CRM1 and CLTC (PubMed:16314522). Interacts with PTK6 (PubMed:18719096). Interacts with RPA194 and ACTB (PubMed:21555369). Interacts with PRKCABP, SRC and MYOC (By similarity). Interacts (preferentially with the tyrosine phosphorylated form) with CPNE3; this interaction occurs at the cell membrane and is increased in a growth factor heregulin-dependent manner (PubMed:20010870). Interacts with HSP90AA1 and HSP90AB1 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (PubMed:26517842).By similarity15 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

WithEntry#Exp.IntActNotes
itself12EBI-641062,EBI-641062
ABL1P005192EBI-641062,EBI-375543
ABL2P426846EBI-641062,EBI-1102694
ACPPP153092EBI-641062,EBI-1222012
ACTBP6070910EBI-641062,EBI-353944
ANKS1AQ926252EBI-641062,EBI-1048612
APBB1O002132EBI-641062,EBI-81694
BCAR3O758152EBI-641062,EBI-702336
CDC37Q165433EBI-641062,EBI-295634
CISHQ9NSE24EBI-641062,EBI-617866
CLNKQ7Z7G12EBI-641062,EBI-7878194
CRKLP461092EBI-641062,EBI-910
CUL5Q930342EBI-641062,EBI-1057139
DOK1Q997042EBI-641062,EBI-1384360
DOK4Q8TEW62EBI-641062,EBI-6918542
EEA1Q150755EBI-641062,EBI-298113
EFNB1P9817211EBI-641062,EBI-538287
EGFRP0053325EBI-641062,EBI-297353
ERBB3P2186029EBI-641062,EBI-720706
ERBB4Q153034EBI-641062,EBI-80371
ERRFI1Q9UJM33EBI-641062,EBI-2941912
FGRP097693EBI-641062,EBI-1383732
FYNP062412EBI-641062,EBI-515315
GRAP2O757912EBI-641062,EBI-740418
GRB2P629934EBI-641062,EBI-401755
GRB7Q144515EBI-641062,EBI-970191
H2AFYO753676EBI-641062,EBI-2868511
H2AFYO75367-33EBI-641062,EBI-6250866
HSP90AA1P079005EBI-641062,EBI-296047
HSP90AB1P082383EBI-641062,EBI-352572
HSP90B1P146252EBI-641062,EBI-359129
IQGAP1P469405EBI-641062,EBI-297509
IRS1P355682EBI-641062,EBI-517592
ITKQ088812EBI-641062,EBI-968552
JAK1P234582EBI-641062,EBI-1383438
KPNB1Q1497414EBI-641062,EBI-286758
MAPK8IP1Q9UQF23EBI-641062,EBI-78404
MAPK8IP2Q133873EBI-641062,EBI-722813
MATKP426792EBI-641062,EBI-751664
MEMO1Q9Y3166EBI-641062,EBI-1104564
NCK2O436392EBI-641062,EBI-713635
NRG1Q02297-72EBI-641062,EBI-2460927
PIK3C2BO007502EBI-641062,EBI-641107
PIK3R1P2798611EBI-641062,EBI-79464
PIK3R2O004596EBI-641062,EBI-346930
PIK3R3Q925699EBI-641062,EBI-79893
PLCG1P191745EBI-641062,EBI-79387
PLCG2P168853EBI-641062,EBI-617403
POLR1AO9560216EBI-641062,EBI-359472
PTK2Q053972EBI-641062,EBI-702142
PTK6Q138824EBI-641062,EBI-1383632
PTPN11Q061242EBI-641062,EBI-297779
PTPN12Q052094EBI-641062,EBI-2266035
PTPN18Q999526EBI-641062,EBI-1384210
PTPN18Q99952-15EBI-641062,EBI-12739708
PTPRBP234672EBI-641062,EBI-1265766
PTPRCP085752EBI-641062,EBI-1341
PTPRJQ129132EBI-641062,EBI-2264500
PTPRKQ152622EBI-641062,EBI-474052
PTPROQ168272EBI-641062,EBI-723739
RANBP2P497923EBI-641062,EBI-973138
RASA1P209368EBI-641062,EBI-1026476
RECKO959804EBI-641062,EBI-2823742
SH2D2AQ9NP312EBI-641062,EBI-490630
SHC1P293539EBI-641062,EBI-78835
SHC2P980773EBI-641062,EBI-7256023
SHC3Q925292EBI-641062,EBI-79084
SLA2Q9H6Q32EBI-641062,EBI-1222854
SOCS1O155242EBI-641062,EBI-968198
SRCP1293111EBI-641062,EBI-621482
STAT1P422243EBI-641062,EBI-1057697
STAT3P407639EBI-641062,EBI-518675
SUPT6HQ7KZ852EBI-641062,EBI-2515547
SYKP434057EBI-641062,EBI-78302
TLN1Q9Y4903EBI-641062,EBI-2462036
TNS2Q63HR24EBI-641062,EBI-949753
TNS3Q68CZ22EBI-641062,EBI-1220488
VAV1Q96D372EBI-641062,EBI-7875353
VAV2P527353EBI-641062,EBI-297549
XPO1O149802EBI-641062,EBI-355867

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
108376, 253 interactors

CORUM comprehensive resource of mammalian protein complexes

More...
CORUMi
P04626

Database of interacting proteins

More...
DIPi
DIP-8N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...
ELMi
P04626

Protein interaction database and analysis system

More...
IntActi
P04626, 251 interactors

Molecular INTeraction database

More...
MINTi
P04626

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000269571

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
P04626

<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

11255
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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SMRi
P04626

Database of comparative protein structure models

More...
ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
P04626

<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>Domaini720 – 987Protein kinasePROSITE-ProRule annotationAdd BLAST268

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni676 – 689Required for interaction with KPNB1 and EEA11 PublicationAdd BLAST14
Regioni1195 – 1197Interaction with PIK3C2BCurated3

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 – 689Nuclear localization signalAdd BLAST14

<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

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG1025 Eukaryota
ENOG410XNSR LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000158232

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000230982

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
P04626

KEGG Orthology (KO)

More...
KOi
K05083

Identification of Orthologs from Complete Genome Data

More...
OMAi
WDQDPSE

Database of Orthologous Groups

More...
OrthoDBi
1575614at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
P04626

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, 3 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>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (6+)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 6 <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 and alternative initiation. AlignAdd to basket

This entry has 6 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P04626-1) [UniParc]FASTAAdd to basket
Also known as: ERBB2, HER2

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
MELAALCRWG LLLALLPPGA ASTQVCTGTD MKLRLPASPE THLDMLRHLY
60 70 80 90 100
QGCQVVQGNL ELTYLPTNAS LSFLQDIQEV QGYVLIAHNQ VRQVPLQRLR
110 120 130 140 150
IVRGTQLFED NYALAVLDNG DPLNNTTPVT GASPGGLREL QLRSLTEILK
160 170 180 190 200
GGVLIQRNPQ LCYQDTILWK DIFHKNNQLA LTLIDTNRSR ACHPCSPMCK
210 220 230 240 250
GSRCWGESSE DCQSLTRTVC AGGCARCKGP LPTDCCHEQC AAGCTGPKHS
260 270 280 290 300
DCLACLHFNH SGICELHCPA LVTYNTDTFE SMPNPEGRYT FGASCVTACP
310 320 330 340 350
YNYLSTDVGS CTLVCPLHNQ EVTAEDGTQR CEKCSKPCAR VCYGLGMEHL
360 370 380 390 400
REVRAVTSAN IQEFAGCKKI FGSLAFLPES FDGDPASNTA PLQPEQLQVF
410 420 430 440 450
ETLEEITGYL YISAWPDSLP DLSVFQNLQV IRGRILHNGA YSLTLQGLGI
460 470 480 490 500
SWLGLRSLRE LGSGLALIHH NTHLCFVHTV PWDQLFRNPH QALLHTANRP
510 520 530 540 550
EDECVGEGLA CHQLCARGHC WGPGPTQCVN CSQFLRGQEC VEECRVLQGL
560 570 580 590 600
PREYVNARHC LPCHPECQPQ NGSVTCFGPE ADQCVACAHY KDPPFCVARC
610 620 630 640 650
PSGVKPDLSY MPIWKFPDEE GACQPCPINC THSCVDLDDK GCPAEQRASP
660 670 680 690 700
LTSIISAVVG ILLVVVLGVV FGILIKRRQQ KIRKYTMRRL LQETELVEPL
710 720 730 740 750
TPSGAMPNQA QMRILKETEL RKVKVLGSGA FGTVYKGIWI PDGENVKIPV
760 770 780 790 800
AIKVLRENTS PKANKEILDE AYVMAGVGSP YVSRLLGICL TSTVQLVTQL
810 820 830 840 850
MPYGCLLDHV RENRGRLGSQ DLLNWCMQIA KGMSYLEDVR LVHRDLAARN
860 870 880 890 900
VLVKSPNHVK ITDFGLARLL DIDETEYHAD GGKVPIKWMA LESILRRRFT
910 920 930 940 950
HQSDVWSYGV TVWELMTFGA KPYDGIPARE IPDLLEKGER LPQPPICTID
960 970 980 990 1000
VYMIMVKCWM IDSECRPRFR ELVSEFSRMA RDPQRFVVIQ NEDLGPASPL
1010 1020 1030 1040 1050
DSTFYRSLLE DDDMGDLVDA EEYLVPQQGF FCPDPAPGAG GMVHHRHRSS
1060 1070 1080 1090 1100
STRSGGGDLT LGLEPSEEEA PRSPLAPSEG AGSDVFDGDL GMGAAKGLQS
1110 1120 1130 1140 1150
LPTHDPSPLQ RYSEDPTVPL PSETDGYVAP LTCSPQPEYV NQPDVRPQPP
1160 1170 1180 1190 1200
SPREGPLPAA RPAGATLERP KTLSPGKNGV VKDVFAFGGA VENPEYLTPQ
1210 1220 1230 1240 1250
GGAAPQPHPP PAFSPAFDNL YYWDQDPPER GAPPSTFKGT PTAENPEYLG

LDVPV
Length:1,255
Mass (Da):137,910
Last modified:August 13, 1987 - 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:i39E9DFDA04DCF962
GO
Isoform 2 (identifier: P04626-2) [UniParc]FASTAAdd to basket
Also known as: CTF-611

The sequence of this isoform differs from the canonical sequence as follows:
     1-610: Missing.

Note: Produced by alternative initiation at Met-611 of isoform 1.
Show »
Length:645
Mass (Da):70,917
Checksum:i288AFEFB6D101A34
GO
Isoform 3 (identifier: P04626-3) [UniParc]FASTAAdd to basket
Also known as: CTF-687

The sequence of this isoform differs from the canonical sequence as follows:
     1-686: Missing.

Note: Produced by alternative initiation at Met-687 of isoform 1.
Show »
Length:569
Mass (Da):62,568
Checksum:i090ABCB192CE1E73
GO
Isoform 4 (identifier: P04626-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: MELAALCRWGLLLALLPPGAAST → MPRGSWKP

Note: Produced by alternative splicing of isoform 1.
Show »
Length:1,240
Mass (Da):136,501
Checksum:i1C679DD67798C0DE
GO
Isoform 5 (identifier: P04626-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: Missing.

Note: No experimental confirmation available. Gene prediction based on partial mRNA and EST data.
Show »
Length:1,225
Mass (Da):134,856
Checksum:i09B9238293C83D80
GO
Isoform 6 (identifier: P04626-6) [UniParc]FASTAAdd to basket
Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     633-648: Missing.
     771-883: AYVMAGVGSP...ETEYHADGGK → TISNLFSNFA...LMCPQGAGKA
     884-1255: Missing.

Show »
Length:888
Mass (Da):97,382
Checksum:iB2A5C268C58767E5
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 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3QLU9J3QLU9_HUMAN
Receptor protein-tyrosine kinase
ERBB2
1,055Annotation score:

Annotation score:3 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>
B4DTR1B4DTR1_HUMAN
Receptor protein-tyrosine kinase
ERBB2
979Annotation score:

Annotation score:3 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>
F5H1T4F5H1T4_HUMAN
Receptor tyrosine-protein kinase er...
ERBB2
603Annotation 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>
J3KTI5J3KTI5_HUMAN
Receptor tyrosine-protein kinase er...
ERBB2
251Annotation 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>
J3QRX1J3QRX1_HUMAN
Receptor tyrosine-protein kinase er...
ERBB2
166Annotation 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>
J3QRJ7J3QRJ7_HUMAN
Receptor tyrosine-protein kinase er...
ERBB2
177Annotation 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>
J3QL83J3QL83_HUMAN
Receptor tyrosine-protein kinase er...
ERBB2
90Annotation 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>
J3KRI9J3KRI9_HUMAN
Receptor tyrosine-protein kinase er...
ERBB2
96Annotation 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>
J3QLV2J3QLV2_HUMAN
Receptor tyrosine-protein kinase er...
ERBB2
102Annotation 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>

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

There are four alleles due to the variations in positions 654 and 655. Allele B1 (Ile-654/Ile-655) has a frequency of 0.782; allele B2 (Ile-654/Val-655) has a frequency of 0.206; allele B3 (Val-654/Val-655) has a frequency of 0.012.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_016317452W → C1 PublicationCorresponds to variant dbSNP:rs4252633Ensembl.1
Natural variantiVAR_004077654I → V in allele B3. 2 PublicationsCorresponds to variant dbSNP:rs1801201Ensembl.1
Natural variantiVAR_004078655I → V in allele B2 and allele B3. 3 PublicationsCorresponds to variant dbSNP:rs1136201Ensembl.1
Natural variantiVAR_055432755L → P in LNCR; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs121913469Ensembl.1
Natural variantiVAR_042097768L → S1 PublicationCorresponds to variant dbSNP:rs56366519Ensembl.1
Natural variantiVAR_055433774M → MAYVM in LNCR; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_042098776G → S in GASC; somatic mutation; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs28933369Ensembl.1
Natural variantiVAR_055434779S → SVGS in LNCR; somatic mutation; unknown pathological significance. 1 Publication1
Natural variantiVAR_042099857N → S in OC; somatic mutation; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs28933370Ensembl.1
Natural variantiVAR_055435914E → K in GLM; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs28933368Ensembl.1
Natural variantiVAR_0163181170P → A4 PublicationsCorresponds to variant dbSNP:rs1058808Ensembl.1
Natural variantiVAR_0421001216A → D1 PublicationCorresponds to variant dbSNP:rs55943169Ensembl.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.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0392501 – 686Missing in isoform 3. CuratedAdd BLAST686
Alternative sequenceiVSP_0392491 – 610Missing in isoform 2. CuratedAdd BLAST610
Alternative sequenceiVSP_0547871 – 30Missing in isoform 5. CuratedAdd BLAST30
Alternative sequenceiVSP_0392481 – 23MELAA…GAAST → MPRGSWKP in isoform 4. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_055902633 – 648Missing in isoform 6. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_055903771 – 883AYVMA…ADGGK → TISNLFSNFAPRGPSACCEP TCWCHSGKGQDSLPREEWGR QRRFCLWGCRGEPRVLDTPG RSCPSAPPSSCLQPSLRQPL LLGPGPTRAGGSTQHLQRDT YGREPRVPGSGRASVNQKAK SAEALMCPQGAGKA in isoform 6. 1 PublicationAdd BLAST113
Alternative sequenceiVSP_055904884 – 1255Missing in isoform 6. 1 PublicationAdd BLAST372

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
AH001455 Genomic DNA Translation: AAA35808.1
X03363 mRNA Translation: CAA27060.1
M11730 mRNA Translation: AAA75493.1
M12036 Genomic DNA Translation: AAA35978.1
AY208911 Genomic DNA Translation: AAO18082.1
AK295195 mRNA Translation: BAG58195.1
CH471152 Genomic DNA Translation: EAW60597.1
BC167147 mRNA Translation: AAI67147.1
M16792
, M16789, M16790, M16791 Genomic DNA Translation: AAA58637.1
KJ534964 mRNA Translation: AHW56604.1
L29395 Genomic DNA Translation: AAA35809.1
M95667 Genomic DNA Translation: AAC37531.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS32642.1 [P04626-1]
CCDS45667.1 [P04626-5]
CCDS74052.1 [P04626-4]

Protein sequence database of the Protein Information Resource

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PIRi
A24571

NCBI Reference Sequences

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RefSeqi
NP_001005862.1, NM_001005862.2 [P04626-5]
NP_001276865.1, NM_001289936.1 [P04626-4]
NP_001276867.1, NM_001289938.1
NP_004439.2, NM_004448.3 [P04626-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000269571; ENSP00000269571; ENSG00000141736 [P04626-1]
ENST00000406381; ENSP00000385185; ENSG00000141736 [P04626-5]
ENST00000541774; ENSP00000446466; ENSG00000141736 [P04626-4]
ENST00000584601; ENSP00000462438; ENSG00000141736 [P04626-5]

Database of genes from NCBI RefSeq genomes

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GeneIDi
2064

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:2064

UCSC genome browser

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UCSCi
uc060esv.1 human [P04626-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Chromosomal rearrangement, 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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
Wikipedia

ERBB2 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AH001455 Genomic DNA Translation: AAA35808.1
X03363 mRNA Translation: CAA27060.1
M11730 mRNA Translation: AAA75493.1
M12036 Genomic DNA Translation: AAA35978.1
AY208911 Genomic DNA Translation: AAO18082.1
AK295195 mRNA Translation: BAG58195.1
CH471152 Genomic DNA Translation: EAW60597.1
BC167147 mRNA Translation: AAI67147.1
M16792
, M16789, M16790, M16791 Genomic DNA Translation: AAA58637.1
KJ534964 mRNA Translation: AHW56604.1
L29395 Genomic DNA Translation: AAA35809.1
M95667 Genomic DNA Translation: AAC37531.1
CCDSiCCDS32642.1 [P04626-1]
CCDS45667.1 [P04626-5]
CCDS74052.1 [P04626-4]
PIRiA24571
RefSeqiNP_001005862.1, NM_001005862.2 [P04626-5]
NP_001276865.1, NM_001289936.1 [P04626-4]
NP_001276867.1, NM_001289938.1
NP_004439.2, NM_004448.3 [P04626-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1MFGX-ray1.25B1247-1255[»]
1MFLX-ray1.88B1247-1255[»]
1MW4NMR-B1135-1144[»]
1N8ZX-ray2.52C23-629[»]
1OVCmodel-A737-1031[»]
1QR1X-ray2.40C/F654-662[»]
1S78X-ray3.25A/B23-646[»]
2A91X-ray2.50A22-530[»]
2JWANMR-A/B641-684[»]
2KS1NMR-A641-684[»]
2L4KNMR-B1135-1144[»]
2N2ANMR-A/B644-700[»]
3BE1X-ray2.90A23-646[»]
3H3BX-ray2.45A/B23-214[»]
3MZWX-ray2.90A23-646[»]
3N85X-ray3.20A23-646[»]
3PP0X-ray2.25A/B703-1029[»]
3RCDX-ray3.21A/B/C/D713-1028[»]
3WLWX-ray3.09A/B23-586[»]
3WSQX-ray3.50A23-586[»]
4GFUX-ray2.00F1246-1252[»]
4HRLX-ray2.55C24-219[»]
4HRMX-ray3.20A/C24-219[»]
4HRNX-ray2.65C/D529-625[»]
5K33X-ray3.30C23-629[»]
5KWGX-ray4.30C23-653[»]
5MY6X-ray2.25A24-645[»]
5O4GX-ray3.00C23-628[»]
5OB4NMR-A/B641-684[»]
5TQSX-ray1.88E/F/G/H1218-1228[»]
6ATTX-ray3.77A23-652[»]
6BGTX-ray2.70C1-652[»]
6J71X-ray2.92A22-639[»]
SMRiP04626
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108376, 253 interactors
CORUMiP04626
DIPiDIP-8N
ELMiP04626
IntActiP04626, 251 interactors
MINTiP04626
STRINGi9606.ENSP00000269571

Chemistry databases

BindingDBiP04626
ChEMBLiCHEMBL1824
DrugBankiDB08916 Afatinib
DB04988 IGN311
DB01259 Lapatinib
DB06366 Pertuzumab
DB00072 Trastuzumab
DB05773 Trastuzumab emtansine
DB05007 XL647
GuidetoPHARMACOLOGYi2019

Protein family/group databases

MoonDBiP04626 Predicted

PTM databases

CarbonylDBiP04626
GlyConnecti1710
iPTMnetiP04626
PhosphoSitePlusiP04626

Polymorphism and mutation databases

BioMutaiERBB2
DMDMi119533

Proteomic databases

EPDiP04626
jPOSTiP04626
PaxDbiP04626
PeptideAtlasiP04626
PRIDEiP04626
ProteomicsDBi51718
51719 [P04626-2]
51720 [P04626-3]
51721 [P04626-4]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
2064
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269571; ENSP00000269571; ENSG00000141736 [P04626-1]
ENST00000406381; ENSP00000385185; ENSG00000141736 [P04626-5]
ENST00000541774; ENSP00000446466; ENSG00000141736 [P04626-4]
ENST00000584601; ENSP00000462438; ENSG00000141736 [P04626-5]
GeneIDi2064
KEGGihsa:2064
UCSCiuc060esv.1 human [P04626-1]

Organism-specific databases

Comparative Toxicogenomics Database

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CTDi
2064
DisGeNETi2064

GeneCards: human genes, protein and diseases

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GeneCardsi
ERBB2
HGNCiHGNC:3430 ERBB2
HPAiCAB000043
CAB020416
CAB062555
HPA001060
HPA001338
HPA001383
MalaCardsiERBB2
MIMi137800 phenotype
164870 gene
167000 phenotype
211980 phenotype
613659 phenotype
neXtProtiNX_P04626
OpenTargetsiENSG00000141736
PharmGKBiPA27844

GenAtlas: human gene database

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GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1025 Eukaryota
ENOG410XNSR LUCA
GeneTreeiENSGT00940000158232
HOGENOMiHOG000230982
InParanoidiP04626
KOiK05083
OMAiWDQDPSE
OrthoDBi1575614at2759
PhylomeDBiP04626
TreeFamiTF106002

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-1227986 Signaling by ERBB2
R-HSA-1250196 SHC1 events in ERBB2 signaling
R-HSA-1251932 PLCG1 events in ERBB2 signaling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1306955 GRB7 events in ERBB2 signaling
R-HSA-1358803 Downregulation of ERBB2:ERBB3 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-416572 Sema4D induced cell migration and growth-cone collapse
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-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
SignaLinkiP04626
SIGNORiP04626

Miscellaneous databases

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

More...
ChiTaRSi
ERBB2 human
EvolutionaryTraceiP04626

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
HER2/neu

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

More...
GenomeRNAii
2064
PMAP-CutDBiP04626

Protein Ontology

More...
PROi
PR:P04626

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000141736 Expressed in 212 organ(s), highest expression level in esophagus mucosa
ExpressionAtlasiP04626 baseline and differential
GenevisibleiP04626 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, 3 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

More...
ProtoNeti
Search...

<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 nameiERBB2_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: P04626
Secondary accession number(s): B2RZG3
, B4DHN3, Q14256, Q6LDV1, Q9UMK4, X5D2V5
<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: August 13, 1987
Last sequence update: August 13, 1987
Last modified: June 5, 2019
This is version 245 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  8. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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