Skip to main content
  •   Home
  •   Download
  •   Manual
  •   Contact

Molecule Details

General Information of the Molecule
Name
Tyrosine kinase receptor Erbb2 (HER2)
Synonyms
Proto-oncogene Neu; Erbb2 tyrosine kinase receptor; p185erbB2; Tyrosine kinase-type cell surface receptor HER2; Receptor tyrosine-protein kinase erbB-2; Proto-oncogene c-ErbB-2; Proto-oncogene Neu; NGL; NEU; Metastatic lymph node gene 19 protein; MLN19; MLN 19; HER2; CD340
Gene Name
ERBB2
Gene ID
2064
Sequence
MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNL
ELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNG
DPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLA
LTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQC
AAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACP
YNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSAN
IQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLP
DLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTV
PWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQEC
VEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARC
PSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVG
ILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETEL
RKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSP
YVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVR
LVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFT
HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWM
IDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDA
EEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEG
AGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYV
NQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQ
GGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV
    Click to Show/Hide
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.
    Click to Show/Hide
Uniprot ID
ERBB2_HUMAN
EC Number
EC: 2.7.10.1
Pfam
PF00757 ; PF14843 ; PF07714 ; PF01030
KEGG ID
hsa2064
TTD ID
T14597
A List of Drug Combination(s) Able to Regulate This Molecule
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Celastrol   NP Info  + Trastuzumab   Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Expression of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Apigenin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Expression of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Trastuzumab   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Flavopiridol   NP Info  + Depsipeptide   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Expression of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Hesperetin   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Expression of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + Tamoxifen   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Expression of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Celastrol   NP Info  + Lapatinib   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Thymoquinone   NP Info  + Cyclophosphamide   Drug Info 
                    Structure +
          Phosphorylation Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Phosphorylation of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Dasatinib   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Cucurbitacin B  NP Info  Investigative Cucurbitaceae
2 Magnolol  NP Info  Investigative Magnolia officinalis
Drug(s) of This Target
1 Afatinib  Drug Info  Approved Lung cancer
2 Lapatinib  Drug Info  Approved Breast cancer
3 Methylseleninic acid  Drug Info  Investigative Breast cancer
4 Trastuzumab  Drug Info  Approved Breast cancer
References
Reference 1 Anticancer activity of Celastrol in combination with ErbB2-targeted therapeutics for treatment of ErbB2-overexpressing breast cancers. Cancer Biol Ther. 2011 Jan 15;11(2):263-76.
Reference 2 5-Fluorouracil combined with apigenin enhances anticancer activity through induction of apoptosis in human breast cancer MDA-MB-453 cells. Oncol Rep. 2009 Dec;22(6):1533-7.
Reference 3 The chemomodulatory effects of resveratrol and didox on herceptin cytotoxicity in breast cancer cell lines. Sci Rep. 2015 Jul 9;5:12054.
Reference 4 Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: activation of the mitochondria-dependent death-signaling pathway. J Thorac Cardiovasc Surg. 2003 May;125(5):1132-42.
Reference 5 Cytotoxic and Antimetastatic Activity of Hesperetin and Doxorubicin Combination Toward Her2 Expressing Breast Cancer Cells. Asian Pac J Cancer Prev. 2020 May 1;21(5):1259-1267.
Reference 6 Tamoxifen and genistein synergistically down-regulate signal transduction and proliferation in estrogen receptor-negative human breast carcinoma MDA-MB-435 cells. Anticancer Res. May-Jun 1999;19(3A):1657-62.
Reference 7 Downregulation and subcellular distribution of HER2 involved in MDA-MB-453 breast cancer cell apoptosis induced by lapatinib/celastrol combination. J BUON. May-Jun 2017;22(3):644-651.
Reference 8 Thymoquinone Augments Cyclophosphamide-Mediated Inhibition of Cell Proliferation in Breast Cancer Cells. Asian Pac J Cancer Prev. 2019 Apr 29;20(4):1153-1160.
Reference 9 Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. Int J Cancer. 2011 Feb 15;128(4):951-61.
Reference 10 HER2 mediated de novo production of TGFBeta leads to SNAIL driven epithelial-to-mesenchymal transition and metastasis of breast cancer. Mol Oncol. 2014 Dec;8(8):1532-47.
Reference 11 Magnolol down-regulates HER2 gene expression, leading to inhibition of HER2-mediated metastatic potential in ovarian cancer cells. Cancer Lett. 2011 Dec 1;311(1):11-9.
Reference 12 Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
Reference 13 Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
Reference 14 Curcumin Enhances the Antitumoral Effect Induced by the Recombinant Vaccinia Neu Vaccine (rV- neu T) in Mice with Transplanted Salivary Gland Carcinoma Cells. Nutrients. 2020 May 14;12(5):1417.
Reference 15 Her2/neu is not a commonly expressed therapeutic target in melanoma -- a large cohort tissue microarray study. Melanoma Res. 2004 Jun;14(3):207-10.
Cite NPCDR
Visitor Map
Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China