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P04626

- ERBB2_HUMAN

UniProt

P04626 - ERBB2_HUMAN

Protein

Receptor tyrosine-protein kinase erbB-2

Gene

ERBB2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 194 (01 Oct 2014)
      Sequence version 1 (13 Aug 1987)
      Previous versions | rss
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    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.
    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.

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.1 PublicationPROSITE-ProRule annotation

    Enzyme 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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei753 – 7531ATPPROSITE-ProRule annotation
    Active sitei845 – 8451Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi726 – 7349ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. epidermal growth factor-activated receptor activity Source: UniProtKB
    3. ErbB-3 class receptor binding Source: ProtInc
    4. identical protein binding Source: IntAct
    5. protein binding Source: UniProtKB
    6. protein C-terminus binding Source: UniProtKB
    7. protein dimerization activity Source: UniProtKB
    8. protein heterodimerization activity Source: UniProtKB
    9. protein phosphatase binding Source: UniProtKB
    10. protein tyrosine kinase activity Source: BHF-UCL
    11. receptor signaling protein tyrosine kinase activity Source: ProtInc
    12. RNA polymerase I core binding Source: UniProtKB
    13. transmembrane receptor protein tyrosine kinase activity Source: BHF-UCL
    14. transmembrane signaling receptor activity Source: BHF-UCL

    GO - Biological processi

    1. axon guidance Source: Reactome
    2. cell proliferation Source: ProtInc
    3. cell surface receptor signaling pathway Source: MGI
    4. enzyme linked receptor protein signaling pathway Source: ProtInc
    5. epidermal growth factor receptor signaling pathway Source: Reactome
    6. Fc-epsilon receptor signaling pathway Source: Reactome
    7. fibroblast growth factor receptor signaling pathway Source: Reactome
    8. heart development Source: UniProtKB
    9. innate immune response Source: Reactome
    10. mammary gland development Source: UniProtKB
    11. motor neuron axon guidance Source: Ensembl
    12. myelination Source: Ensembl
    13. negative regulation of immature T cell proliferation in thymus Source: Ensembl
    14. nervous system development Source: UniProtKB
    15. neuromuscular junction development Source: Ensembl
    16. neurotrophin TRK receptor signaling pathway Source: Reactome
    17. peptidyl-tyrosine phosphorylation Source: GOC
    18. peripheral nervous system development Source: Ensembl
    19. phosphatidylinositol 3-kinase signaling Source: BHF-UCL
    20. phosphatidylinositol-mediated signaling Source: UniProtKB
    21. positive regulation of cell adhesion Source: BHF-UCL
    22. positive regulation of cell growth Source: UniProtKB
    23. positive regulation of epithelial cell proliferation Source: UniProtKB
    24. positive regulation of MAP kinase activity Source: UniProtKB
    25. positive regulation of protein phosphorylation Source: BHF-UCL
    26. positive regulation of Rho GTPase activity Source: BHF-UCL
    27. positive regulation of transcription from RNA polymerase III promoter Source: UniProtKB
    28. positive regulation of transcription from RNA polymerase I promoter Source: UniProtKB
    29. positive regulation of translation Source: UniProtKB
    30. protein autophosphorylation Source: BHF-UCL
    31. protein phosphorylation Source: ProtInc
    32. regulation of angiogenesis Source: UniProtKB
    33. regulation of ERK1 and ERK2 cascade Source: UniProtKB
    34. regulation of microtubule-based process Source: UniProtKB
    35. signal transduction Source: UniProtKB
    36. signal transduction by phosphorylation Source: GOC
    37. transcription, DNA-templated Source: UniProtKB-KW
    38. transmembrane receptor protein tyrosine kinase signaling pathway Source: BHF-UCL
    39. wound healing Source: BHF-UCL

    Keywords - Molecular functioni

    Activator, Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_115662. Downregulation of ERBB2:ERBB3 signaling.
    REACT_115720. PLCG1 events in ERBB2 signaling.
    REACT_115755. Signaling by ERBB2.
    REACT_115854. GRB2 events in ERBB2 signaling.
    REACT_115896. GRB7 events in ERBB2 signaling.
    REACT_115993. SHC1 events in ERBB2 signaling.
    REACT_116008. PI3K events in ERBB2 signaling.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_19277. Sema4D induced cell migration and growth-cone collapse.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinkiP04626.

    Names & Taxonomyi

    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
    Gene namesi
    Name:ERBB2
    Synonyms:HER2, MLN19, NEU, NGL
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:3430. ERBB2.

    Subcellular locationi

    Isoform 1 : Cell membrane; Single-pass type I membrane protein. Cytoplasmperinuclear region. Nucleus
    Note: Translocation to the nucleus requires endocytosis, probably endosomal sorting and is mediated by importin beta-1/KPNB1.

    GO - Cellular componenti

    1. apical plasma membrane Source: Ensembl
    2. basolateral plasma membrane Source: BHF-UCL
    3. cytoplasm Source: HPA
    4. cytoplasmic vesicle Source: Ensembl
    5. endosome membrane Source: UniProtKB
    6. integral component of membrane Source: UniProtKB
    7. membrane Source: InterPro
    8. nucleus Source: UniProtKB
    9. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    10. plasma membrane Source: UniProtKB
    11. receptor complex Source: BHF-UCL

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Hereditary diffuse gastric cancer (HDGC) [MIM:137215]: A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start 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.
    Note: The gene represented in this entry is involved in disease pathogenesis.
    Glioma (GLM) [MIM:137800]: Gliomas 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.
    Note: The gene represented in this entry is involved in disease pathogenesis.
    Ovarian cancer (OC) [MIM:167000]: The 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.
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Lung cancer (LNCR) [MIM:211980]: A 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.
    Note: The gene represented in this entry is involved in disease pathogenesis.
    Gastric cancer (GASC) [MIM:613659]: A 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.
    Note: The gene represented in this entry is involved in disease pathogenesis.
    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.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi317 – 3182LH → AA: Reduces dimerization with ERBB3. 1 Publication
    Mutagenesisi611 – 6111M → A: Prevents synthesis of isoform 2. 2 Publications
    Mutagenesisi687 – 6871M → A: Prevents synthesis of isoform 3. 2 Publications
    Mutagenesisi706 – 7061M → A: No effect on isoform production. 2 Publications
    Mutagenesisi712 – 7121M → A: No effect on isoform production. 2 Publications

    Organism-specific databases

    MIMi137215. phenotype.
    137800. phenotype.
    167000. phenotype.
    211980. phenotype.
    613659. phenotype.
    PharmGKBiPA27844.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2222Sequence AnalysisAdd
    BLAST
    Chaini23 – 12551233Receptor tyrosine-protein kinase erbB-2PRO_0000016669Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi26 ↔ 53
    Glycosylationi68 – 681N-linked (GlcNAc...)1 Publication
    Glycosylationi124 – 1241N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi162 ↔ 192
    Glycosylationi187 – 1871N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi195 ↔ 204
    Disulfide bondi199 ↔ 212
    Disulfide bondi220 ↔ 227
    Disulfide bondi224 ↔ 235
    Disulfide bondi236 ↔ 244
    Disulfide bondi240 ↔ 252
    Disulfide bondi255 ↔ 264
    Glycosylationi259 – 2591N-linked (GlcNAc...)3 Publications
    Disulfide bondi268 ↔ 295
    Disulfide bondi299 ↔ 311
    Disulfide bondi315 ↔ 331
    Disulfide bondi334 ↔ 338
    Disulfide bondi342 ↔ 367
    Disulfide bondi475 ↔ 504
    Disulfide bondi511 ↔ 520
    Disulfide bondi515 ↔ 528
    Glycosylationi530 – 5301N-linked (GlcNAc...)2 Publications
    Disulfide bondi531 ↔ 540
    Disulfide bondi544 ↔ 560
    Disulfide bondi563 ↔ 576
    Disulfide bondi567 ↔ 584
    Glycosylationi571 – 5711N-linked (GlcNAc...)1 Publication
    Disulfide bondi587 ↔ 596
    Disulfide bondi600 ↔ 623
    Disulfide bondi626 ↔ 634By similarity
    Glycosylationi629 – 6291N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi630 ↔ 642By similarity
    Modified residuei1054 – 10541Phosphoserine3 Publications
    Modified residuei1107 – 11071Phosphoserine1 Publication
    Modified residuei1139 – 11391Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei1196 – 11961PhosphotyrosineSequence Analysis
    Modified residuei1248 – 12481Phosphotyrosine; by autocatalysis2 Publications

    Post-translational modificationi

    Autophosphorylated. Ligand-binding increases phosphorylation on tyrosine residues. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Signaling via SEMA4C promotes phosphorylation at Tyr-1248.6 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiP04626.
    PaxDbiP04626.
    PRIDEiP04626.

    PTM databases

    PhosphoSiteiP04626.

    Miscellaneous databases

    PMAP-CutDBP04626.

    Expressioni

    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

    ArrayExpressiP04626.
    BgeeiP04626.
    CleanExiHS_ERBB2.
    GenevestigatoriP04626.

    Organism-specific databases

    HPAiCAB000043.
    CAB020416.
    CAB062555.
    HPA001338.
    HPA001383.

    Interactioni

    Subunit structurei

    Homodimer. Heterodimer with EGFR, ERBB3 and ERBB4. Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1196. Interacts with PRKCABP and PLXNB1. Interacts (when phosphorylated on Tyr-1248) with MEMO1. Interacts with MUC1; the interaction is enhanced by heregulin (HRG). Interacts (when phosphorylated on Tyr-1139) with GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1248) with ERBB2IP. Interacts with KPNB1, RANBP2, EEA1, CRM1, CLTC, PTK6, RPA94 and ACTB. Interacts with SRC and MYOC By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself7EBI-641062,EBI-641062
    ABL1P005192EBI-641062,EBI-375543
    ABL2P426846EBI-641062,EBI-1102694
    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
    DOK1Q997042EBI-641062,EBI-1384360
    DOK4Q8TEW62EBI-641062,EBI-6918542
    EEA1Q150755EBI-641062,EBI-298113
    EFNB1P9817211EBI-641062,EBI-538287
    EGFRP0053318EBI-641062,EBI-297353
    ERBB3P2186021EBI-641062,EBI-720706
    ERBB4Q153032EBI-641062,EBI-80371
    FGRP097693EBI-641062,EBI-1383732
    FYNP062412EBI-641062,EBI-515315
    GRAP2O757912EBI-641062,EBI-740418
    GRB2P629933EBI-641062,EBI-401755
    GRB7Q144515EBI-641062,EBI-970191
    H2AFYO753676EBI-641062,EBI-2868511
    H2AFYO75367-33EBI-641062,EBI-6250866
    HSP90AA1P079003EBI-641062,EBI-296047
    HSP90AB1P082383EBI-641062,EBI-352572
    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
    PTK6Q138822EBI-641062,EBI-1383632
    PTPN11Q061242EBI-641062,EBI-297779
    PTPN12Q052094EBI-641062,EBI-2266035
    PTPRBP234672EBI-641062,EBI-1265766
    PTPRCP085752EBI-641062,EBI-1341
    PTPRJQ129132EBI-641062,EBI-2264500
    PTPRKQ152622EBI-641062,EBI-474052
    PTPROQ168272EBI-641062,EBI-723739
    RANBP2P497923EBI-641062,EBI-973138
    RASA1P209367EBI-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
    TENC1Q63HR24EBI-641062,EBI-949753
    TLN1Q9Y4903EBI-641062,EBI-2462036
    TNS3Q68CZ22EBI-641062,EBI-1220488
    VAV1Q96D372EBI-641062,EBI-7875353
    VAV2P527353EBI-641062,EBI-297549
    XPO1O149802EBI-641062,EBI-355867

    Protein-protein interaction databases

    BioGridi108376. 115 interactions.
    DIPiDIP-8N.
    IntActiP04626. 192 interactions.
    MINTiMINT-158636.
    STRINGi9606.ENSP00000269571.

    Structurei

    Secondary structure

    1
    1255
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi25 – 273
    Helixi39 – 5012
    Beta strandi54 – 585
    Beta strandi60 – 645
    Helixi72 – 743
    Beta strandi79 – 824
    Beta strandi84 – 885
    Beta strandi92 – 954
    Turni109 – 1113
    Beta strandi112 – 1176
    Turni130 – 1323
    Beta strandi139 – 1413
    Beta strandi150 – 1567
    Turni164 – 1663
    Helixi169 – 1724
    Helixi175 – 1773
    Beta strandi182 – 1843
    Beta strandi199 – 2024
    Beta strandi204 – 2085
    Helixi209 – 2113
    Beta strandi217 – 2193
    Beta strandi221 – 2233
    Beta strandi227 – 2315
    Helixi232 – 2343
    Beta strandi240 – 2489
    Beta strandi251 – 26010
    Beta strandi263 – 2675
    Beta strandi271 – 2744
    Turni276 – 2783
    Beta strandi281 – 2833
    Beta strandi289 – 2913
    Beta strandi294 – 2985
    Beta strandi303 – 3053
    Beta strandi309 – 3146
    Beta strandi320 – 3234
    Beta strandi325 – 3273
    Beta strandi329 – 3324
    Beta strandi335 – 3373
    Helixi348 – 3525
    Turni358 – 3603
    Helixi361 – 3644
    Beta strandi368 – 3769
    Helixi378 – 3825
    Helixi385 – 3873
    Helixi396 – 4027
    Beta strandi405 – 4084
    Beta strandi410 – 4134
    Helixi423 – 4253
    Turni438 – 4403
    Beta strandi441 – 4477
    Beta strandi463 – 4697
    Helixi482 – 4854
    Beta strandi486 – 4883
    Beta strandi493 – 4997
    Helixi501 – 5066
    Turni507 – 5093
    Helixi516 – 5183
    Beta strandi520 – 5245
    Helixi525 – 5273
    Beta strandi528 – 5369
    Beta strandi539 – 5424
    Beta strandi545 – 5517
    Beta strandi553 – 5564
    Beta strandi559 – 5624
    Beta strandi571 – 5733
    Beta strandi575 – 5806
    Beta strandi583 – 59210
    Beta strandi595 – 5995
    Beta strandi602 – 6043
    Beta strandi615 – 6173
    Beta strandi621 – 6255
    Beta strandi628 – 6325
    Beta strandi635 – 6373
    Helixi651 – 67828
    Helixi717 – 7193
    Beta strandi720 – 7289
    Beta strandi730 – 73910
    Beta strandi748 – 7558
    Helixi761 – 77414
    Beta strandi785 – 79915
    Helixi806 – 8127
    Turni814 – 8163
    Helixi819 – 83820
    Helixi848 – 8503
    Beta strandi851 – 8555
    Beta strandi858 – 8614
    Helixi886 – 8883
    Helixi891 – 8966
    Helixi901 – 91616
    Turni922 – 9254
    Helixi928 – 9303
    Helixi931 – 9366
    Helixi949 – 95810
    Helixi963 – 9653
    Helixi969 – 98012
    Helixi983 – 9864
    Helixi989 – 9924
    Helixi1003 – 10086
    Beta strandi1140 – 11423

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    3BE1X-ray2.90A23-646[»]
    3H3BX-ray2.45A/B23-214[»]
    3MZWX-ray2.90A23-646[»]
    3N85X-ray3.20A23-646[»]
    3PP0X-ray2.25A/B703-1009[»]
    3RCDX-ray3.21A/B/C/D713-1028[»]
    4GFUX-ray2.00F1246-1252[»]
    4HRLX-ray2.55C24-219[»]
    4HRMX-ray3.20A/C24-219[»]
    4HRNX-ray2.65C/D529-625[»]
    ProteinModelPortaliP04626.
    SMRiP04626. Positions 22-629, 641-1009.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP04626.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini23 – 652630ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini676 – 1255580CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei653 – 67523HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini720 – 987268Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni676 – 68914Nuclear localization signalAdd
    BLAST
    Regioni676 – 68914Required for interaction with KPNB1 and EEA1Add
    BLAST
    Regioni1195 – 11973Interaction with PIK3C2BCurated

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000230982.
    HOVERGENiHBG000490.
    InParanoidiP04626.
    KOiK05083.
    OMAiACYPLCA.
    OrthoDBiEOG7V49XM.
    PhylomeDBiP04626.
    TreeFamiTF106002.

    Family and domain databases

    Gene3Di3.80.20.20. 2 hits.
    InterProiIPR000494. EGF_rcpt_L.
    IPR006211. Furin-like_Cys-rich_dom.
    IPR006212. Furin_repeat.
    IPR009030. Growth_fac_rcpt_N_dom.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
    [Graphical view]
    PfamiPF00757. Furin-like. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF01030. Recep_L_domain. 2 hits.
    [Graphical view]
    PIRSFiPIRSF000619. TyrPK_EGF-R. 1 hit.
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00261. FU. 3 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    SSF57184. SSF57184. 2 hits.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view]

    Sequences (6)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 6 isoformsi produced by alternative splicing and alternative initiation. Align

    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

    MELAALCRWG LLLALLPPGA ASTQVCTGTD MKLRLPASPE THLDMLRHLY     50
    QGCQVVQGNL ELTYLPTNAS LSFLQDIQEV QGYVLIAHNQ VRQVPLQRLR 100
    IVRGTQLFED NYALAVLDNG DPLNNTTPVT GASPGGLREL QLRSLTEILK 150
    GGVLIQRNPQ LCYQDTILWK DIFHKNNQLA LTLIDTNRSR ACHPCSPMCK 200
    GSRCWGESSE DCQSLTRTVC AGGCARCKGP LPTDCCHEQC AAGCTGPKHS 250
    DCLACLHFNH SGICELHCPA LVTYNTDTFE SMPNPEGRYT FGASCVTACP 300
    YNYLSTDVGS CTLVCPLHNQ EVTAEDGTQR CEKCSKPCAR VCYGLGMEHL 350
    REVRAVTSAN IQEFAGCKKI FGSLAFLPES FDGDPASNTA PLQPEQLQVF 400
    ETLEEITGYL YISAWPDSLP DLSVFQNLQV IRGRILHNGA YSLTLQGLGI 450
    SWLGLRSLRE LGSGLALIHH NTHLCFVHTV PWDQLFRNPH QALLHTANRP 500
    EDECVGEGLA CHQLCARGHC WGPGPTQCVN CSQFLRGQEC VEECRVLQGL 550
    PREYVNARHC LPCHPECQPQ NGSVTCFGPE ADQCVACAHY KDPPFCVARC 600
    PSGVKPDLSY MPIWKFPDEE GACQPCPINC THSCVDLDDK GCPAEQRASP 650
    LTSIISAVVG ILLVVVLGVV FGILIKRRQQ KIRKYTMRRL LQETELVEPL 700
    TPSGAMPNQA QMRILKETEL RKVKVLGSGA FGTVYKGIWI PDGENVKIPV 750
    AIKVLRENTS PKANKEILDE AYVMAGVGSP YVSRLLGICL TSTVQLVTQL 800
    MPYGCLLDHV RENRGRLGSQ DLLNWCMQIA KGMSYLEDVR LVHRDLAARN 850
    VLVKSPNHVK ITDFGLARLL DIDETEYHAD GGKVPIKWMA LESILRRRFT 900
    HQSDVWSYGV TVWELMTFGA KPYDGIPARE IPDLLEKGER LPQPPICTID 950
    VYMIMVKCWM IDSECRPRFR ELVSEFSRMA RDPQRFVVIQ NEDLGPASPL 1000
    DSTFYRSLLE DDDMGDLVDA EEYLVPQQGF FCPDPAPGAG GMVHHRHRSS 1050
    STRSGGGDLT LGLEPSEEEA PRSPLAPSEG AGSDVFDGDL GMGAAKGLQS 1100
    LPTHDPSPLQ RYSEDPTVPL PSETDGYVAP LTCSPQPEYV NQPDVRPQPP 1150
    SPREGPLPAA RPAGATLERP KTLSPGKNGV VKDVFAFGGA VENPEYLTPQ 1200
    GGAAPQPHPP PAFSPAFDNL YYWDQDPPER GAPPSTFKGT PTAENPEYLG 1250
    LDVPV 1255
    Length:1,255
    Mass (Da):137,910
    Last modified:August 13, 1987 - v1
    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:887
    Mass (Da):97,253
    Checksum:iC1F3CB76B3760220
    GO

    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)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti452 – 4521W → C.1 Publication
    Corresponds to variant rs4252633 [ dbSNP | Ensembl ].
    VAR_016317
    Natural varianti654 – 6541I → V in allele B3. 2 Publications
    Corresponds to variant rs1801201 [ dbSNP | Ensembl ].
    VAR_004077
    Natural varianti655 – 6551I → V in allele B2 and allele B3. 3 Publications
    Corresponds to variant rs1136201 [ dbSNP | Ensembl ].
    VAR_004078
    Natural varianti755 – 7551L → P in a lung adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_055432
    Natural varianti768 – 7681L → S.1 Publication
    Corresponds to variant rs56366519 [ dbSNP | Ensembl ].
    VAR_042097
    Natural varianti774 – 7741M → MAYVM in a lung adenocarcinoma sample; somatic mutation.
    VAR_055433
    Natural varianti776 – 7761G → S in a gastric adenocarcinoma sample; somatic mutation. 2 Publications
    Corresponds to variant rs28933369 [ dbSNP | Ensembl ].
    VAR_042098
    Natural varianti779 – 7791S → SVGS in a lung adenocarcinoma sample; somatic mutation.
    VAR_055434
    Natural varianti857 – 8571N → S in an ovarian cancer sample; somatic mutation. 2 Publications
    Corresponds to variant rs28933370 [ dbSNP | Ensembl ].
    VAR_042099
    Natural varianti914 – 9141E → K in a glioblastoma sample; somatic mutation. 1 Publication
    Corresponds to variant rs28933368 [ dbSNP | Ensembl ].
    VAR_055435
    Natural varianti1170 – 11701P → A.4 Publications
    Corresponds to variant rs61552325 [ dbSNP | Ensembl ].
    VAR_016318
    Natural varianti1216 – 12161A → D.1 Publication
    Corresponds to variant rs55943169 [ dbSNP | Ensembl ].
    VAR_042100

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 686686Missing in isoform 3. CuratedVSP_039250Add
    BLAST
    Alternative sequencei1 – 610610Missing in isoform 2. CuratedVSP_039249Add
    BLAST
    Alternative sequencei1 – 3030Missing in isoform 5. CuratedVSP_054787Add
    BLAST
    Alternative sequencei1 – 2323MELAA…GAAST → MPRGSWKP in isoform 4. 1 PublicationVSP_039248Add
    BLAST
    Alternative sequencei633 – 64816Missing in isoform 6. 1 PublicationVSP_055902Add
    BLAST
    Alternative sequencei771 – 883113AYVMA…ADGGK → TISNLFSNFAPRGPSACCPT CWCHSGKGQDSLPREEWGRQ RRFCLWGCRGEPRVLDTPGR SCPSAPPSSCLQPSLRQPLL LGPGPTRAGGSTQHLQRDTY GREPRVPGSGRASVNQKAKS AEALMCPQGAGKA in isoform 6. 1 PublicationVSP_055903Add
    BLAST
    Alternative sequencei884 – 1255372Missing in isoform 6. 1 PublicationVSP_055904Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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]
    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]
    XP_005257197.1. XM_005257140.1. [P04626-5]
    UniGeneiHs.446352.

    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.
    UCSCiuc002hsm.3. human. [P04626-1]
    uc010cwa.3. human. [P04626-4]

    Polymorphism databases

    DMDMi119533.

    Keywords - Coding sequence diversityi

    Alternative initiation, Alternative splicing, Chromosomal rearrangement, Polymorphism

    Cross-referencesi

    Web resourcesi

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

    ERBB2 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS32642.1. [P04626-1 ]
    CCDS45667.1. [P04626-5 ]
    PIRi A24571.
    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 ]
    XP_005257197.1. XM_005257140.1. [P04626-5 ]
    UniGenei Hs.446352.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1MFG X-ray 1.25 B 1247-1255 [» ]
    1MFL X-ray 1.88 B 1247-1255 [» ]
    1MW4 NMR - B 1135-1144 [» ]
    1N8Z X-ray 2.52 C 23-629 [» ]
    1OVC model - A 737-1031 [» ]
    1QR1 X-ray 2.40 C/F 654-662 [» ]
    1S78 X-ray 3.25 A/B 23-646 [» ]
    2A91 X-ray 2.50 A 22-530 [» ]
    2JWA NMR - A/B 641-684 [» ]
    2KS1 NMR - A 641-684 [» ]
    2L4K NMR - B 1135-1144 [» ]
    3BE1 X-ray 2.90 A 23-646 [» ]
    3H3B X-ray 2.45 A/B 23-214 [» ]
    3MZW X-ray 2.90 A 23-646 [» ]
    3N85 X-ray 3.20 A 23-646 [» ]
    3PP0 X-ray 2.25 A/B 703-1009 [» ]
    3RCD X-ray 3.21 A/B/C/D 713-1028 [» ]
    4GFU X-ray 2.00 F 1246-1252 [» ]
    4HRL X-ray 2.55 C 24-219 [» ]
    4HRM X-ray 3.20 A/C 24-219 [» ]
    4HRN X-ray 2.65 C/D 529-625 [» ]
    ProteinModelPortali P04626.
    SMRi P04626. Positions 22-629, 641-1009.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108376. 115 interactions.
    DIPi DIP-8N.
    IntActi P04626. 192 interactions.
    MINTi MINT-158636.
    STRINGi 9606.ENSP00000269571.

    Chemistry

    BindingDBi P04626.
    ChEMBLi CHEMBL1824.
    DrugBanki DB01259. Lapatinib.
    DB01006. Letrozole.
    DB00072. Trastuzumab.
    GuidetoPHARMACOLOGYi 2019.

    PTM databases

    PhosphoSitei P04626.

    Polymorphism databases

    DMDMi 119533.

    Proteomic databases

    MaxQBi P04626.
    PaxDbi P04626.
    PRIDEi P04626.

    Protocols and materials databases

    DNASUi 2064.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000269571 ; ENSP00000269571 ; ENSG00000141736 . [P04626-1 ]
    ENST00000406381 ; ENSP00000385185 ; ENSG00000141736 . [P04626-5 ]
    ENST00000541774 ; ENSP00000446466 ; ENSG00000141736 . [P04626-4 ]
    ENST00000584601 ; ENSP00000462438 ; ENSG00000141736 . [P04626-5 ]
    GeneIDi 2064.
    KEGGi hsa:2064.
    UCSCi uc002hsm.3. human. [P04626-1 ]
    uc010cwa.3. human. [P04626-4 ]

    Organism-specific databases

    CTDi 2064.
    GeneCardsi GC17P037844.
    HGNCi HGNC:3430. ERBB2.
    HPAi CAB000043.
    CAB020416.
    CAB062555.
    HPA001338.
    HPA001383.
    MIMi 137215. phenotype.
    137800. phenotype.
    164870. gene.
    167000. phenotype.
    211980. phenotype.
    613659. phenotype.
    neXtProti NX_P04626.
    PharmGKBi PA27844.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000230982.
    HOVERGENi HBG000490.
    InParanoidi P04626.
    KOi K05083.
    OMAi ACYPLCA.
    OrthoDBi EOG7V49XM.
    PhylomeDBi P04626.
    TreeFami TF106002.

    Enzyme and pathway databases

    Reactomei REACT_115662. Downregulation of ERBB2:ERBB3 signaling.
    REACT_115720. PLCG1 events in ERBB2 signaling.
    REACT_115755. Signaling by ERBB2.
    REACT_115854. GRB2 events in ERBB2 signaling.
    REACT_115896. GRB7 events in ERBB2 signaling.
    REACT_115993. SHC1 events in ERBB2 signaling.
    REACT_116008. PI3K events in ERBB2 signaling.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_19277. Sema4D induced cell migration and growth-cone collapse.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinki P04626.

    Miscellaneous databases

    ChiTaRSi ERBB2. human.
    EvolutionaryTracei P04626.
    GeneWikii HER2/neu.
    GenomeRNAii 2064.
    NextBioi 8385.
    PMAP-CutDB P04626.
    PROi P04626.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P04626.
    Bgeei P04626.
    CleanExi HS_ERBB2.
    Genevestigatori P04626.

    Family and domain databases

    Gene3Di 3.80.20.20. 2 hits.
    InterProi IPR000494. EGF_rcpt_L.
    IPR006211. Furin-like_Cys-rich_dom.
    IPR006212. Furin_repeat.
    IPR009030. Growth_fac_rcpt_N_dom.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt.
    [Graphical view ]
    Pfami PF00757. Furin-like. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF01030. Recep_L_domain. 2 hits.
    [Graphical view ]
    PIRSFi PIRSF000619. TyrPK_EGF-R. 1 hit.
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00261. FU. 3 hits.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    SSF57184. SSF57184. 2 hits.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor."
      Yamamoto T., Ikawa S., Akiyama T., Semba K., Nomura N., Miyajima N., Saito T., Toyoshima K.
      Nature 319:230-234(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene."
      Coussens L., Yang-Feng T.L., Liao Y.C., Chen E., Gray A., McGrath J., Seeburg P.H., Libermann T.A., Schlessinger J., Francke U., Levinson A., Ullrich A.
      Science 230:1132-1139(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT ALA-1170.
    3. NIEHS SNPs program
      Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-452; VAL-655 AND ALA-1170.
    4. "NEDO human cDNA sequencing project focused on splicing variants."
      Wakamatsu A., Yamamoto J., Kimura K., Ishii S., Watanabe K., Sugiyama A., Murakawa K., Kaida T., Tsuchiya K., Fukuzumi Y., Kumagai A., Oishi Y., Yamamoto S., Ono Y., Komori Y., Yamazaki M., Kisu Y., Nishikawa T.
      , Sugano S., Nomura N., Isogai T.
      Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
      Tissue: Brain.
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    7. "Human HER2 (neu) promoter: evidence for multiple mechanisms for transcriptional initiation."
      Tal M., King C.R., Kraus M.H., Ullrich A., Schlessinger J., Givol D.
      Mol. Cell. Biol. 7:2597-2601(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-191 (ISOFORM 1).
    8. "Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism."
      Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M., Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I., Kuang X., Zhao N., Malhotra D., Michaelson J.J.
      , Vacic V., Calderwood M.A., Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D., Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.
      Nat. Commun. 5:3650-3650(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-867 (ISOFORM 6).
      Tissue: Fetal brain.
    9. "A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma."
      Semba K., Kamata N., Toyoshima K., Yamamoto T.
      Proc. Natl. Acad. Sci. U.S.A. 82:6497-6501(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 737-1031.
    10. "Amplification of a novel v-erbB-related gene in a human mammary carcinoma."
      King C.R., Kraus M.H., Aaronson S.A.
      Science 229:974-976(1985) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 832-909.
      Tissue: Mammary carcinoma.
    11. "Molecular cloning and sequencing of an intron of Her-2/neu (ERBB2) gene."
      Sarkar F.H., Ball D.E., Li Y.W., Crissman J.D.
      DNA Cell Biol. 12:611-615(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE OF 1081-1245, VARIANT ALA-1170.
    12. "ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases."
      Olayioye M.A., Beuvink I., Horsch K., Daly J.M., Hynes N.E.
      J. Biol. Chem. 274:17209-17218(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ERBB4, FUNCTION IN ACTIVATION OF STAT5A.
    13. "Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors."
      Arcaro A., Zvelebil M.J., Wallasch C., Ullrich A., Waterfield M.D., Domin J.
      Mol. Cell. Biol. 20:3817-3830(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A COMPLEX WITH PIK3C2A AND EGFR, IDENTIFICATION IN A COMPLEX WITH PIK3C2B AND EGFR, INTERACTION WITH PIK3C2B.
    14. "Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein."
      Li Y., Yu W.-H., Ren J., Chen W., Huang L., Kharbanda S., Loda M., Kufe D.
      Mol. Cancer Res. 1:765-775(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MUC1.
    15. "Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2."
      Wang S.C., Lien H.C., Xia W., Chen I.F., Lo H.W., Wang Z., Ali-Seyed M., Lee D.F., Bartholomeusz G., Ou-Yang F., Giri D.K., Hung M.C.
      Cancer Cell 6:251-261(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    16. "Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2."
      Swiercz J.M., Kuner R., Offermanns S.
      J. Cell Biol. 165:869-880(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PLXNB1.
    17. Cited for: INTERACTION WITH MEMO1.
    18. "Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor."
      Giri D.K., Ali-Seyed M., Li L.Y., Lee D.F., Ling P., Bartholomeusz G., Wang S.C., Hung M.C.
      Mol. Cell. Biol. 25:11005-11018(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, INTERACTION WITH KPNB1; RANBP2; CRM1; EEA1 AND CLTC.
    19. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1248, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    20. "Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation of translation."
      Anido J., Scaltriti M., Bech Serra J.J., Santiago Josefat B., Todo F.R., Baselga J., Arribas J.
      EMBO J. 25:3234-3244(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ALTERNATIVE INITIATION (ISOFORMS 2 AND 3), SUBCELLULAR LOCATION, MUTAGENESIS OF MET-611; MET-687; MET-706 AND MET-712.
    21. "Neuregulin-1 only induces trans-phosphorylation between ErbB receptor heterodimer partners."
      Li Z., Mei Y., Liu X., Zhou M.
      Cell. Signal. 19:466-471(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ERBB4, AUTOPHOSPHORYLATION IN TRANS.
    22. "Plexin-B2, but not Plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo."
      Deng S., Hirschberg A., Worzfeld T., Penachioni J.Y., Korostylev A., Swiercz J.M., Vodrazka P., Mauti O., Stoeckli E.T., Tamagnone L., Offermanns S., Kuner R.
      J. Neurosci. 27:6333-6347(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-1248.
    23. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1054, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    24. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1054, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    25. Cited for: INTERACTION WITH PTK6, ENZYME REGULATION.
    26. "ErbB2-mediated Src and signal transducer and activator of transcription 3 activation leads to transcriptional up-regulation of p21Cip1 and chemoresistance in breast cancer cells."
      Hawthorne V.S., Huang W.C., Neal C.L., Tseng L.M., Hung M.C., Yu D.
      Mol. Cancer Res. 7:592-600(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN NUCLEUS.
    27. "ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells."
      Zaoui K., Benseddik K., Daou P., Salaun D., Badache A.
      Proc. Natl. Acad. Sci. U.S.A. 107:18517-18522(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    28. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1107, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    29. "Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing."
      Zang Z.J., Ong C.K., Cutcutache I., Yu W., Zhang S.L., Huang D., Ler L.D., Dykema K., Gan A., Tao J., Lim S., Liu Y., Futreal P.A., Grabsch H., Furge K.A., Goh L.K., Rozen S., Teh B.T., Tan P.
      Cancer Res. 71:29-39(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHROMOSOMAL REARRANGEMENT WITH CDK12.
    30. "Nuclear ErbB2 enhances translation and cell growth by activating transcription of ribosomal RNA genes."
      Li L.Y., Chen H., Hsieh Y.H., Wang Y.N., Chu H.J., Chen Y.H., Chen H.Y., Chien P.J., Ma H.T., Tsai H.C., Lai C.C., Sher Y.P., Lien H.C., Tsai C.H., Hung M.C.
      Cancer Res. 71:4269-4279(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN NUCLEUS, INTERACTION WITH ACTB AND RPA194, SUBCELLULAR LOCATION.
    31. "Dissociation of epidermal growth factor receptor and ErbB2 heterodimers in the presence of somatostatin receptor 5 modulate signaling pathways."
      Kharmate G., Rajput P.S., Watt H.L., Somvanshi R.K., Chaudhari N., Qiu X., Kumar U.
      Endocrinology 152:931-945(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EGFR.
    32. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1054, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    33. "Poor binding of a HER-2/neu epitope (GP2) to HLA-A2.1 is due to a lack of interactions with the center of the peptide."
      Kuhns J.J., Batalia M.A., Yan S., Collins E.J.
      J. Biol. Chem. 274:36422-36427(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 654-662 IN COMPLEX WITH HLA AND BETA-2 MICROGLOBULIN.
    34. "Novel mode of ligand recognition by the Erbin PDZ domain."
      Birrane G., Chung J., Ladias J.A.
      J. Biol. Chem. 278:1399-1402(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 1247-1255 IN COMPLEX WITH ERBB2IP, INTERACTION WITH ERBB2IP.
    35. "Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2."
      Ivancic M., Daly R.J., Lyons B.A.
      J. Biomol. NMR 27:205-219(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1135-1144 IN COMPLEX WITH GRB7, INTERACTION WITH GRB7.
    36. "Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab."
      Cho H.-S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B., Denney D.W. Jr., Leahy D.J.
      Nature 421:756-760(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 23-629 IN COMPLEX WITH THE ANTIBODY HERCEPTIN.
    37. "Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex."
      Franklin M.C., Carey K.D., Vajdos F.F., Leahy D.J., de Vos A.M., Sliwkowski M.X.
      Cancer Cell 5:317-328(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 23-646 IN COMPLEX WITH THE ANTIBODY PERTUZUMAB, INTERACTION WITH ERBB3, MUTAGENESIS OF 317-LEU-HIS-318, DISULFIDE BONDS, GLYCOSYLATION AT ASN-187; ASN-259 AND ASN-530.
    38. "Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site."
      Bostrom J., Yu S.F., Kan D., Appleton B.A., Lee C.V., Billeci K., Man W., Peale F., Ross S., Wiesmann C., Fuh G.
      Science 323:1610-1614(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 23-646 IN COMPLEX WITH THE ANTIBODY HERCEPTIN, DISULFIDE BONDS, GLYCOSYLATION AT ASN-259 AND ASN-530.
    39. "Structural basis for high-affinity HER2 receptor binding by an engineered protein."
      Eigenbrot C., Ultsch M., Dubnovitsky A., Abrahmsen L., Hard T.
      Proc. Natl. Acad. Sci. U.S.A. 107:15039-15044(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 23-646 IN COMPLEX WITH ENGINEERED ANTIBODY ZHER2, DISULFIDE BONDS, GLYCOSYLATION AT ASN-68; ASN-259 AND ASN-571.
    40. "Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein."
      Aertgeerts K., Skene R., Yano J., Sang B.C., Zou H., Snell G., Jennings A., Iwamoto K., Habuka N., Hirokawa A., Ishikawa T., Tanaka T., Miki H., Ohta Y., Sogabe S.
      J. Biol. Chem. 286:18756-18765(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 703-1029 IN COMPLEX WITH INHIBITOR SYR127063, CATALYTIC ACTIVITY, SUBUNIT, ENZYME REGULATION.
    41. "Characterization of a new allele of the human ERBB2 gene by allele-specific competition hybridization."
      Ehsani A., Low J., Wallace R.B., Wu A.M.
      Genomics 15:426-429(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS VAL-654 AND VAL-655.
    42. "Lung cancer: intragenic ERBB2 kinase mutations in tumours."
      Cancer genome project and collaborative group
      Stephens P., Hunter C., Bignell G., Edkins S., Davies H., Teague J., Stevens C., O'Meara S., Smith R., Parker A., Barthorpe A., Blow M., Brackenbury L., Butler A., Clarke O., Cole J., Dicks E., Dike A.
      , Drozd A., Edwards K., Forbes S., Foster R., Gray K., Greenman C., Halliday K., Hills K., Kosmidou V., Lugg R., Menzies A., Perry J., Petty R., Raine K., Ratford L., Shepherd R., Small A., Stephens Y., Tofts C., Varian J., West S., Widaa S., Yates A., Brasseur F., Cooper C.S., Flanagan A.M., Knowles M., Leung S.Y., Louis D.N., Looijenga L.H., Malkowicz B., Pierotti M.A., Teh B., Chenevix-Trench G., Weber B.L., Yuen S.T., Harris G., Goldstraw P., Nicholson A.G., Futreal P.A., Wooster R., Stratton M.R.
      Nature 431:525-526(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PRO-755; SER-776; ALA-TYR-VAL-MET-774 INS AND VAL-GLY-SER-779 INS; SER-857 AND LYS-914, INVOLVEMENT IN CANCER.
    43. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-654; VAL-655; SER-768; SER-776; SER-857; ALA-1170 AND ASP-1216.

    Entry informationi

    Entry nameiERBB2_HUMAN
    AccessioniPrimary (citable) accession number: P04626
    Secondary accession number(s): B2RZG3
    , B4DHN3, Q14256, Q6LDV1, Q9UMK4, X5D2V5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 13, 1987
    Last sequence update: August 13, 1987
    Last modified: October 1, 2014
    This is version 194 of the entry and version 1 of the sequence. [Complete history]
    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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    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 and mouse protein kinases
      Human and mouse protein kinases: classification and index
    8. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3