Receptor tyrosine-protein kinase erbB-2

Details

Name
Receptor tyrosine-protein kinase erbB-2
Synonyms
  • 2.7.10.1
  • HER2
  • Metastatic lymph node gene 19 protein
  • MLN 19
  • MLN19
  • NEU
  • NGL
  • p185erbB2
  • Proto-oncogene c-ErbB-2
  • Proto-oncogene Neu
  • Tyrosine kinase-type cell surface receptor HER2
Gene Name
ERBB2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001020|Receptor tyrosine-protein kinase erbB-2
MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNL
ELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNG
DPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLA
LTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQC
AAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACP
YNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSAN
IQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLP
DLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTV
PWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQEC
VEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARC
PSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVG
ILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETEL
RKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSP
YVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVR
LVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFT
HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWM
IDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDA
EEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEG
AGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYV
NQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQ
GGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV
Number of residues
1255
Molecular Weight
137909.27
Theoretical pI
5.76
GO Classification
Functions
ATP binding / ErbB-3 class receptor binding / identical protein binding / protein C-terminus binding / protein dimerization activity / protein heterodimerization activity / protein phosphatase binding / protein tyrosine kinase activity / receptor signaling protein tyrosine kinase activity / RNA polymerase I core binding / transmembrane receptor protein tyrosine kinase activity / transmembrane signaling receptor activity
Processes
activation of MAPKK activity / axon guidance / cell proliferation / cell surface receptor signaling pathway / cellular response to growth factor stimulus / enzyme linked receptor protein signaling pathway / epidermal growth factor receptor signaling pathway / estrous cycle / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / heart development / innate immune response / insulin receptor signaling pathway / liver development / mammary gland involution / MAPK cascade / motor neuron axon guidance / myelination / negative regulation of apoptotic process / negative regulation of immature T cell proliferation in thymus / neuromuscular junction development / neurotrophin TRK receptor signaling pathway / oligodendrocyte differentiation / peptidyl-tyrosine phosphorylation / peripheral nervous system development / phosphatidylinositol 3-kinase signaling / phosphatidylinositol-mediated signaling / positive regulation of cell adhesion / positive regulation of cell growth / positive regulation of epithelial cell proliferation / positive regulation of GTPase activity / positive regulation of MAP kinase activity / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of protein phosphorylation / positive regulation of protein targeting to membrane / positive regulation of Ras protein signal transduction / positive regulation of transcription from RNA polymerase I promoter / positive regulation of transcription from RNA polymerase III promoter / positive regulation of translation / protein autophosphorylation / protein phosphorylation / Ras protein signal transduction / regulation of angiogenesis / regulation of ERK1 and ERK2 cascade / regulation of microtubule-based process / response to axon injury / response to drug / response to progesterone / signal transduction / skeletal muscle tissue development / small GTPase mediated signal transduction / sympathetic nervous system development / tongue development / transcription, DNA-templated / transmembrane receptor protein tyrosine kinase signaling pathway / vascular endothelial growth factor receptor signaling pathway / wound healing
Components
apical plasma membrane / basal plasma membrane / basolateral plasma membrane / cytoplasm / cytoplasmic vesicle / endosome membrane / integral component of membrane / lateral loop / membrane raft / microvillus / nucleus / perinuclear region of cytoplasm / plasma membrane / postsynaptic membrane / receptor complex
General Function
Transmembrane signaling receptor activity
Specific Function
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.
Pfam Domain Function
Transmembrane Regions
653-675
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010360|Receptor tyrosine-protein kinase erbB-2 (ERBB2)
ATGAAGCTGCGGCTCCCTGCCAGTCCCGAGACCCACCTGGACATGCTCCGCCACCTCTAC
CAGGGCTGCCAGGTGGTGCAGGGAAACCTGGAACTCACCTACCTGCCCACCAATGCCAGC
CTGTCCTTCCTGCAGGATATCCAGGAGGTGCAGGGCTACGTGCTCATCGCTCACAACCAA
GTGAGGCAGGTCCCACTGCAGAGGCTGCGGATTGTGCGAGGCACCCAGCTCTTTGAGGAC
AACTATGCCCTGGCCGTGCTAGACAATGGAGACCCGCTGAACAATACCACCCCTGTCACA
GGGGCCTCCCCAGGAGGCCTGCGGGAGCTGCAGCTTCGAAGCCTCACAGAGATCTTGAAA
GGAGGGGTCTTGATCCAGCGGAACCCCCAGCTCTGCTACCAGGACACGATTTTGTGGAAG
GACATCTTCCACAAGAACAACCAGCTGGCTCTCACACTGATAGACACCAACCGCTCTCGG
GCCTGCCACCCCTGTTCTCCGATGTGTAAGGGCTCCCGCTGCTGGGGAGAGAGTTCTGAG
GATTGTCAGAGCCTGACGCGCACTGTCTGTGCCGGTGGCTGTGCCCGCTGCAAGGGGCCA
CTGCCCACTGACTGCTGCCATGAGCAGTGTGCTGCCGGCTGCACGGGCCCCAAGCACTCT
GACTGCCTGGCCTGCCTCCACTTCAACCACAGTGGCATCTGTGAGCTGCACTGCCCAGCC
CTGGTCACCTACAACACAGACACGTTTGAGTCCATGCCCAATCCCGAGGGCCGGTATACA
TTCGGCGCCAGCTGTGTGACTGCCTGTCCCTACAACTACCTTTCTACGGACGTGGGATCC
TGCACCCTCGTCTGCCCCCTGCACAACCAAGAGGTGACAGCAGAGGATGGAACACAGCGG
TGTGAGAAGTGCAGCAAGCCCTGTGCCCGAGTGTGCTATGGTCTGGGCATGGAGCACTTG
CGAGAGGTGAGGGCAGTTACCAGTGCCAATATCCAGGAGTTTGCTGGCTGCAAGAAGATC
TTTGGGAGCCTGGCATTTCTGCCGGAGAGCTTTGATGGGGACCCAGCCTCCAACACTGCC
CCGCTCCAGCCAGAGCAGCTCCAAGTGTTTGAGACTCTGGAAGAGATCACAGGTTACCTA
TACATCTCAGCATGGCCGGACAGCCTGCCTGACCTCAGCGTCTTCCAGAACCTGCAAGTA
ATCCGGGGACGAATTCTGCACAATGGCGCCTACTCGCTGACCCTGCAAGGGCTGGGCATC
AGCTGGCTGGGGCTGCGCTCACTGAGGGAACTGGGCAGTGGACTGGCCCTCATCCACCAT
AACACCCACCTCTGCTTCGTGCACACGGTGCCCTGGGACCAGCTCTTTCGGAACCCGCAC
CAAGCTCTGCTCCACACTGCCAACCGGCCAGAGGACGAGTGTGTGGGCGAGGGCCTGGCC
TGCCACCAGCTGTGCGCCCGAGGGCACTGCTGGGGTCCAGGGCCCACCCAGTGTGTCAAC
TGCAGCCAGTTCCTTCGGGGCCAGGAGTGCGTGGAGGAATGCCGAGTACTGCAGGGGCTC
CCCAGGGAGTATGTGAATGCCAGGCACTGTTTGCCGTGCCACCCTGAGTGTCAGCCCCAG
AATGGCTCAGTGACCTGTTTTGGACCGGAGGCTGACCAGTGTGTGGCCTGTGCCCACTAT
AAGGACCCTCCCTTCTGCGTGGCCCGCTGCCCCAGCGGTGTGAAACCTGACCTCTCCTAC
ATGCCCATCTGGAAGTTTCCAGATGAGGAGGGCGCATGCCAGCCTTGCCCCATCAACTGC
ACCCACTCCTGTGTGGACCTGGATGACAAGGGCTGCCCCGCCGAGCAGAGAGCCAGCCCT
CTGACGTCCATCATCTCTGCGGTGGTTGGCATTCTGCTGGTCGTGGTCTTGGGGGTGGTC
TTTGGGATCCTCATCAAGCGACGGCAGCAGAAGATCCGGAAGTACACGATGCGGAGACTG
CTGCAGGAAACGGAGCTGGTGGAGCCGCTGACACCTAGCGGAGCGATGCCCAACCAGGCG
CAGATGCGGATCCTGAAAGAGACGGAGCTGAGGAAGGTGAAGGTGCTTGGATCTGGCGCT
TTTGGCACAGTCTACAAGGGCATCTGGATCCCTGATGGGGAGAATGTGAAAATTCCAGTG
GCCATCAAAGTGTTGAGGGAAAACACATCCCCCAAAGCCAACAAAGAAATCTTAGACGAA
GCATACGTGATGGCTGGTGTGGGCTCCCCATATGTCTCCCGCCTTCTGGGCATCTGCCTG
ACATCCACGGTGCAGCTGGTGACACAGCTTATGCCCTATGGCTGCCTCTTAGACCATGTC
CGGGAAAACCGCGGACGCCTGGGCTCCCAGGACCTGCTGAACTGGTGTATGCAGATTGCC
AAGGGGATGAGCTACCTGGAGGATGTGCGGCTCGTACACAGGGACTTGGCCGCTCGGAAC
GTGCTGGTCAAGAGTCCCAACCATGTCAAAATTACAGACTTCGGGCTGGCTCGGCTGCTG
GACATTGACGAGACAGAGTACCATGCAGATGGGGGCAAGGTGCCCATCAAGTGGATGGCG
CTGGAGTCCATTCTCCGCCGGCGGTTCACCCACCAGAGTGATGTGTGGAGTTATGGTGTG
ACTGTGTGGGAGCTGATGACTTTTGGGGCCAAACCTTACGATGGGATCCCAGCCCGGGAG
ATCCCTGACCTGCTGGAAAAGGGGGAGCGGCTGCCCCAGCCCCCCATCTGCACCATTGAT
GTCTACATGATCATGGTCAAATGTTGGATGATTGACTCTGAATGTCGGCCAAGATTCCGG
GAGTTGGTGTCTGAATTCTCCCGCATGGCCAGGGACCCCCAGCGCTTTGTGGTCATCCAG
AATGAGGACTTGGGCCCAGCCAGTCCCTTGGACAGCACCTTCTACCGCTCACTGCTGGAG
GACGATGACATGGGGGACCTGGTGGATGCTGAGGAGTATCTGGTACCCCAGCAGGGCTTC
TTCTGTCCAGACCCTGCCCCGGGCGCTGGGGGCATGGTCCACCACAGGCACCGCAGCTCA
TCTACCAGGAGTGGCGGTGGGGACCTGACACTAGGGCTGGAGCCCTCTGAAGAGGAGGCC
CCCAGGTCTCCACTGGCACCCTCCGAAGGGGCTGGCTCCGATGTATTTGATGGTGACCTG
GGAATGGGGGCAGCCAAGGGGCTGCAAAGCCTCCCCACACATGACCCCAGCCCTCTACAG
CGGTACAGTGAGGACCCCACAGTACCCCTGCCCTCTGAGACTGATGGCTACGTTGCCCCC
CTGACCTGCAGCCCCCAGCCTGAATATGTGAACCAGCCAGATGTTCGGCCCCAGCCCCCT
TCGCCCCGAGAGGGCCCTCTGCCTGCTGCCCGACCTGCTGGTGCCACTCTGGAAAGGCCC
AAGACTCTCTCCCCAGGGAAGAATGGGGTCGTCAAAGACGTTTTTGCCTTTGGGGGTGCC
GTGGAGAACCCCGAGTACTTGACACCCCAGGGAGGAGCTGCCCCTCAGCCCCACCCTCCT
CCTGCCTTCAGCCCAGCCTTCGACAACCTCTATTACTGGGACCAGGACCCACCAGAGCGG
GGGGCTCCACCCAGCACCTTCAAAGGGACACCTACGGCAGAGAACCCAGAGTACCTGGGT
CTGGACGTGCCAGTGTGA
Chromosome Location
17
Locus
17q11.2-q12|17q21.1
External Identifiers
ResourceLink
UniProtKB IDP04626
UniProtKB Entry NameERBB2_HUMAN
GenBank Protein ID553282
GenBank Gene IDM11767
GenAtlas IDERBB2
HGNC IDHGNC:3430
General References
  1. Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T, Toyoshima K: Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986 Jan 16-22;319(6050):230-4. [PubMed:3003577]
  2. Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, et al.: Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985 Dec 6;230(4730):1132-9. [PubMed:2999974]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Tal M, King CR, Kraus MH, Ullrich A, Schlessinger J, Givol D: Human HER2 (neu) promoter: evidence for multiple mechanisms for transcriptional initiation. Mol Cell Biol. 1987 Jul;7(7):2597-601. [PubMed:3039351]
  5. Corominas R, Yang X, Lin GN, Kang S, Shen Y, Ghamsari L, Broly M, Rodriguez M, Tam S, Trigg SA, Fan C, Yi S, Tasan M, Lemmens I, Kuang X, Zhao N, Malhotra D, Michaelson JJ, Vacic V, Calderwood MA, Roth FP, Tavernier J, Horvath S, Salehi-Ashtiani K, Korkin D, Sebat J, Hill DE, Hao T, Vidal M, Iakoucheva LM: Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. Nat Commun. 2014 Apr 11;5:3650. doi: 10.1038/ncomms4650. [PubMed:24722188]
  6. Semba K, Kamata N, Toyoshima K, Yamamoto T: 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. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6497-501. [PubMed:2995967]
  7. King CR, Kraus MH, Aaronson SA: Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science. 1985 Sep 6;229(4717):974-6. [PubMed:2992089]
  8. Sarkar FH, Ball DE, Li YW, Crissman JD: Molecular cloning and sequencing of an intron of Her-2/neu (ERBB2) gene. DNA Cell Biol. 1993 Sep;12(7):611-5. [PubMed:8104414]
  9. Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE: ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases. J Biol Chem. 1999 Jun 11;274(24):17209-18. [PubMed:10358079]
  10. Arcaro A, Zvelebil MJ, Wallasch C, Ullrich A, Waterfield MD, Domin J: Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors. Mol Cell Biol. 2000 Jun;20(11):3817-30. [PubMed:10805725]
  11. Li Y, Yu WH, Ren J, Chen W, Huang L, Kharbanda S, Loda M, Kufe D: Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein. Mol Cancer Res. 2003 Aug;1(10):765-75. [PubMed:12939402]
  12. Wang SC, Lien HC, Xia W, Chen IF, Lo HW, Wang Z, Ali-Seyed M, Lee DF, Bartholomeusz G, Ou-Yang F, Giri DK, Hung MC: Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2. Cancer Cell. 2004 Sep;6(3):251-61. [PubMed:15380516]
  13. Swiercz JM, Kuner R, Offermanns S: Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2. J Cell Biol. 2004 Jun 21;165(6):869-80. [PubMed:15210733]
  14. Marone R, Hess D, Dankort D, Muller WJ, Hynes NE, Badache A: Memo mediates ErbB2-driven cell motility. Nat Cell Biol. 2004 Jun;6(6):515-22. Epub 2004 May 23. [PubMed:15156151]
  15. Giri DK, Ali-Seyed M, Li LY, Lee DF, Ling P, Bartholomeusz G, Wang SC, Hung MC: Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor. Mol Cell Biol. 2005 Dec;25(24):11005-18. [PubMed:16314522]
  16. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983]
  17. Anido J, Scaltriti M, Bech Serra JJ, Santiago Josefat B, Todo FR, Baselga J, Arribas J: Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation of translation. EMBO J. 2006 Jul 12;25(13):3234-44. Epub 2006 Jun 22. [PubMed:16794579]
  18. Li Z, Mei Y, Liu X, Zhou M: Neuregulin-1 only induces trans-phosphorylation between ErbB receptor heterodimer partners. Cell Signal. 2007 Mar;19(3):466-71. Epub 2006 Sep 15. [PubMed:16978839]
  19. Deng S, Hirschberg A, Worzfeld T, Penachioni JY, Korostylev A, Swiercz JM, Vodrazka P, Mauti O, Stoeckli ET, Tamagnone L, Offermanns S, Kuner R: Plexin-B2, but not Plexin-B1, critically modulates neuronal migration and patterning of the developing nervous system in vivo. J Neurosci. 2007 Jun 6;27(23):6333-47. [PubMed:17554007]
  20. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976]
  21. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648]
  22. Xiang B, Chatti K, Qiu H, Lakshmi B, Krasnitz A, Hicks J, Yu M, Miller WT, Muthuswamy SK: Brk is coamplified with ErbB2 to promote proliferation in breast cancer. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12463-8. doi: 10.1073/pnas.0805009105. Epub 2008 Aug 21. [PubMed:18719096]
  23. Hawthorne VS, Huang WC, Neal CL, Tseng LM, Hung MC, Yu D: 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. Mol Cancer Res. 2009 Apr;7(4):592-600. doi: 10.1158/1541-7786.MCR-08-0316. [PubMed:19372587]
  24. Heinrich C, Keller C, Boulay A, Vecchi M, Bianchi M, Sack R, Lienhard S, Duss S, Hofsteenge J, Hynes NE: Copine-III interacts with ErbB2 and promotes tumor cell migration. Oncogene. 2010 Mar 18;29(11):1598-610. doi: 10.1038/onc.2009.456. Epub 2009 Dec 14. [PubMed:20010870]
  25. Zaoui K, Benseddik K, Daou P, Salaun D, Badache A: ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18517-22. doi: 10.1073/pnas.1000975107. Epub 2010 Oct 11. [PubMed:20937854]
  26. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231]
  27. Zang ZJ, Ong CK, Cutcutache I, Yu W, Zhang SL, Huang D, Ler LD, Dykema K, Gan A, Tao J, Lim S, Liu Y, Futreal PA, Grabsch H, Furge KA, Goh LK, Rozen S, Teh BT, Tan P: Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing. Cancer Res. 2011 Jan 1;71(1):29-39. doi: 10.1158/0008-5472.CAN-10-1749. Epub 2010 Nov 19. [PubMed:21097718]
  28. Li LY, Chen H, Hsieh YH, Wang YN, Chu HJ, Chen YH, Chen HY, Chien PJ, Ma HT, Tsai HC, Lai CC, Sher YP, Lien HC, Tsai CH, Hung MC: Nuclear ErbB2 enhances translation and cell growth by activating transcription of ribosomal RNA genes. Cancer Res. 2011 Jun 15;71(12):4269-79. doi: 10.1158/0008-5472.CAN-10-3504. Epub 2011 May 9. [PubMed:21555369]
  29. Kharmate G, Rajput PS, Watt HL, Somvanshi RK, Chaudhari N, Qiu X, Kumar U: Dissociation of epidermal growth factor receptor and ErbB2 heterodimers in the presence of somatostatin receptor 5 modulate signaling pathways. Endocrinology. 2011 Mar;152(3):931-45. doi: 10.1210/en.2010-0940. Epub 2010 Dec 29. [PubMed:21190959]
  30. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [PubMed:21406692]
  31. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  32. Kuhns JJ, Batalia MA, Yan S, Collins EJ: 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. J Biol Chem. 1999 Dec 17;274(51):36422-7. [PubMed:10593938]
  33. Birrane G, Chung J, Ladias JA: Novel mode of ligand recognition by the Erbin PDZ domain. J Biol Chem. 2003 Jan 17;278(3):1399-402. Epub 2002 Nov 19. [PubMed:12444095]
  34. Ivancic M, Daly RJ, Lyons BA: Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2. J Biomol NMR. 2003 Nov;27(3):205-19. [PubMed:12975581]
  35. Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr, Leahy DJ: Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature. 2003 Feb 13;421(6924):756-60. [PubMed:12610629]
  36. Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004 Apr;5(4):317-28. [PubMed:15093539]
  37. Bostrom J, Yu SF, Kan D, Appleton BA, Lee CV, Billeci K, Man W, Peale F, Ross S, Wiesmann C, Fuh G: Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site. Science. 2009 Mar 20;323(5921):1610-4. doi: 10.1126/science.1165480. [PubMed:19299620]
  38. Eigenbrot C, Ultsch M, Dubnovitsky A, Abrahmsen L, Hard T: Structural basis for high-affinity HER2 receptor binding by an engineered protein. Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15039-44. doi: 10.1073/pnas.1005025107. Epub 2010 Aug 9. [PubMed:20696930]
  39. Aertgeerts K, Skene R, Yano J, Sang BC, Zou H, Snell G, Jennings A, Iwamoto K, Habuka N, Hirokawa A, Ishikawa T, Tanaka T, Miki H, Ohta Y, Sogabe S: Structural analysis of the mechanism of inhibition and allosteric activation of the kinase domain of HER2 protein. J Biol Chem. 2011 May 27;286(21):18756-65. doi: 10.1074/jbc.M110.206193. Epub 2011 Mar 30. [PubMed:21454582]
  40. Ehsani A, Low J, Wallace RB, Wu AM: Characterization of a new allele of the human ERBB2 gene by allele-specific competition hybridization. Genomics. 1993 Feb;15(2):426-9. [PubMed:8095488]
  41. 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 CS, Flanagan AM, Knowles M, Leung SY, Louis DN, Looijenga LH, Malkowicz B, Pierotti MA, Teh B, Chenevix-Trench G, Weber BL, Yuen ST, Harris G, Goldstraw P, Nicholson AG, Futreal PA, Wooster R, Stratton MR: Lung cancer: intragenic ERBB2 kinase mutations in tumours. Nature. 2004 Sep 30;431(7008):525-6. [PubMed:15457249]
  42. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, 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 DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [PubMed:17344846]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01259Lapatinibapproved, investigationalyesantagonistDetails
DB00072Trastuzumabapproved, investigationalyesantibodyDetails
DB04988IGN311investigationalunknownDetails
DB11973TesevatinibinvestigationalunknownDetails
DB05773Trastuzumab emtansineapproved, investigationalyesantibodyDetails
DB05944VarlitinibinvestigationalunknownDetails
DB11652TucatinibinvestigationalunknownDetails
DB06021AV-412investigationalunknownDetails
DB06366PertuzumabapprovedyesantibodyDetails
DB08916AfatinibapprovedyesinhibitorDetails
DB12267Brigatinibapproved, investigationalunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails