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P04626

- ERBB2_HUMAN

UniProt

P04626 - ERBB2_HUMAN

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Protein
Receptor tyrosine-protein kinase erbB-2
Gene
ERBB2, HER2, MLN19, NEU, NGL
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.6 Publications
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.6 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.1 Publication

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 – 7531ATP By similarity
Active sitei845 – 8451Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi726 – 7349ATP By similarity

GO - Molecular functioni

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

GO - Biological processi

  1. Fc-epsilon receptor signaling pathway Source: Reactome
  2. axon guidance Source: Reactome
  3. cell proliferation Source: ProtInc
  4. cell surface receptor signaling pathway Source: MGI
  5. enzyme linked receptor protein signaling pathway Source: ProtInc
  6. epidermal growth factor 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 MAP kinase activity Source: UniProtKB
  22. positive regulation of Rho GTPase activity Source: BHF-UCL
  23. positive regulation of cell adhesion Source: BHF-UCL
  24. positive regulation of cell growth Source: UniProtKB
  25. positive regulation of epithelial cell proliferation Source: UniProtKB
  26. positive regulation of protein phosphorylation Source: BHF-UCL
  27. positive regulation of transcription from RNA polymerase I promoter Source: UniProtKB
  28. positive regulation of transcription from RNA polymerase III promoter Source: UniProtKB
  29. positive regulation of translation Source: UniProtKB
  30. protein autophosphorylation Source: BHF-UCL
  31. protein phosphorylation Source: ProtInc
  32. regulation of ERK1 and ERK2 cascade Source: UniProtKB
  33. regulation of angiogenesis 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
Complete GO annotation...

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/KPNB1.4 Publications
Isoform 2 : Cytoplasm. Nucleus 4 Publications
Isoform 3 : Cytoplasm. Nucleus 4 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 652630Extracellular Reviewed prediction
Add
BLAST
Transmembranei653 – 67523Helical; Reviewed prediction
Add
BLAST
Topological domaini676 – 1255580Cytoplasmic Reviewed prediction
Add
BLAST

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. nucleus Source: UniProtKB
  8. perinuclear region of cytoplasm Source: UniProtKB-SubCell
  9. plasma membrane Source: UniProtKB
  10. receptor complex Source: BHF-UCL
Complete GO annotation...

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 – 2222 Reviewed prediction
Add
BLAST
Chaini23 – 12551233Receptor tyrosine-protein kinase erbB-2
PRO_0000016669Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi26 ↔ 533 Publications
Glycosylationi68 – 681N-linked (GlcNAc...)1 Publication
Glycosylationi124 – 1241N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi162 ↔ 1923 Publications
Glycosylationi187 – 1871N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi195 ↔ 2043 Publications
Disulfide bondi199 ↔ 2123 Publications
Disulfide bondi220 ↔ 2273 Publications
Disulfide bondi224 ↔ 2353 Publications
Disulfide bondi236 ↔ 2443 Publications
Disulfide bondi240 ↔ 2523 Publications
Disulfide bondi255 ↔ 2643 Publications
Glycosylationi259 – 2591N-linked (GlcNAc...)3 Publications
Disulfide bondi268 ↔ 2953 Publications
Disulfide bondi299 ↔ 3113 Publications
Disulfide bondi315 ↔ 3313 Publications
Disulfide bondi334 ↔ 3383 Publications
Disulfide bondi342 ↔ 3673 Publications
Disulfide bondi475 ↔ 5043 Publications
Disulfide bondi511 ↔ 5203 Publications
Disulfide bondi515 ↔ 5283 Publications
Glycosylationi530 – 5301N-linked (GlcNAc...)2 Publications
Disulfide bondi531 ↔ 5403 Publications
Disulfide bondi544 ↔ 5603 Publications
Disulfide bondi563 ↔ 5763 Publications
Disulfide bondi567 ↔ 5843 Publications
Glycosylationi571 – 5711N-linked (GlcNAc...)1 Publication
Disulfide bondi587 ↔ 5963 Publications
Disulfide bondi600 ↔ 6233 Publications
Disulfide bondi626 ↔ 634 By similarity
Glycosylationi629 – 6291N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi630 ↔ 642 By similarity
Modified residuei1054 – 10541Phosphoserine3 Publications
Modified residuei1107 – 11071Phosphoserine1 Publication
Modified residuei1139 – 11391Phosphotyrosine; by autocatalysis By similarity
Modified residuei1196 – 11961Phosphotyrosine Reviewed prediction
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-1248.2 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.14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself5EBI-641062,EBI-641062
ABL1P005192EBI-641062,EBI-375543
ABL2P426846EBI-641062,EBI-1102694
ACPPP153093EBI-641062,EBI-1222012
ACTBP6070910EBI-641062,EBI-353944
ANKS1AQ926252EBI-641062,EBI-1048612
APBB1O002132EBI-641062,EBI-81694
BCAR3O758152EBI-641062,EBI-702336
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
EGFRP0053315EBI-641062,EBI-297353
ERBB3P2186020EBI-641062,EBI-720706
ERBB4Q153032EBI-641062,EBI-80371
FGRP097693EBI-641062,EBI-1383732
FYNP062412EBI-641062,EBI-515315
GRB2P629933EBI-641062,EBI-401755
GRB7Q144515EBI-641062,EBI-970191
H2AFYO753676EBI-641062,EBI-2868511
H2AFYO75367-33EBI-641062,EBI-6250866
HSP90AA1P079002EBI-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
PLCG2P168852EBI-641062,EBI-617403
POLR1AO9560216EBI-641062,EBI-359472
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
STAT1P422242EBI-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. 170 interactions.
MINTiMINT-158636.
STRINGi9606.ENSP00000269571.

Structurei

Secondary structure

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.

Miscellaneous databases

EvolutionaryTraceiP04626.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini720 – 987268Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni676 – 68914Nuclear localization signal
Add
BLAST
Regioni676 – 68914Required for interaction with KPNB1 and EEA1
Add
BLAST
Regioni1195 – 11973Interaction with PIK3C2B Inferred

Sequence similaritiesi

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.
VSP_039250Add
BLAST
Alternative sequencei1 – 610610Missing in isoform 2.
VSP_039249Add
BLAST
Alternative sequencei1 – 3030Missing in isoform 5.
VSP_054787Add
BLAST
Alternative sequencei1 – 2323MELAA…GAAST → MPRGSWKP in isoform 4.
VSP_039248Add
BLAST
Alternative sequencei633 – 64816Missing in isoform 6.
VSP_055902Add
BLAST
Alternative sequencei771 – 883113AYVMA…ADGGK → TISNLFSNFAPRGPSACCPT CWCHSGKGQDSLPREEWGRQ RRFCLWGCRGEPRVLDTPGR SCPSAPPSSCLQPSLRQPLL LGPGPTRAGGSTQHLQRDTY GREPRVPGSGRASVNQKAKS AEALMCPQGAGKA in isoform 6.
VSP_055903Add
BLAST
Alternative sequencei884 – 1255372Missing in isoform 6.
VSP_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]
ENST00000541774; ENSP00000446466; ENSG00000141736. [P04626-4]
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. 170 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 ]
ENST00000541774 ; ENSP00000446466 ; ENSG00000141736 . [P04626-4 ]
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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 193 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

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