HER2/neu

HER2/neu
已知的结构 PDB 直系同源搜索: PDBe RCSB PDBID列表 1MFG、​1MFL、​1MW4、​1N8Z、​1QR1、​1S78、​2A91、​2JWA、​2KS1、​2L4K、​3BE1、​3H3B、​3N85、​3PP0、​3RCD、​3MZW、​3WLW、​3WSQ、​4GFU、​4HRL、​4HRM、​4HRN、​2N2A
识别号
别名	ERBB2；, CD340, HER-2, HER-2/neu, HER2, MLN 19, NEU, NGL, TKR1, erb-b2 receptor tyrosine kinase 2
外部ID	OMIM：164870 MGI：95410 HomoloGene：3273 GeneCards：ERBB2
EC number	2.7.10.1
相关疾病
breast carcinoma、​disease of cellular proliferation、​非小细胞肺癌
为以下药物的标靶
阿法替尼、​canertinib、​达科米替尼、​拉帕替尼、​mubritinib、​来那替尼、​玛格妥昔单抗、​达科米替尼、​帕妥珠单抗、​图卡替尼、​bms-599626、​bms-690514、​cp-724714、​cudc-101、​poziotinib、​sapitinib、​varlitinib、​tesevatinib
基因位置（人类） 染色体 17号染色体 基因座 17q12 起始 39,687,914 bp 终止 39,730,426 bp
基因位置（小鼠） 染色体 小鼠11号染色体 基因座 11 61.75 cM|11 D 起始 98,303,296 bp 终止 98,328,542 bp
RNA表达模式
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基因本体 分子功能 • ErbB-3 class receptor binding • 转移酶活性 • 核苷酸结合 • 蛋白激酶活性 • protein dimerization activity • growth factor binding • RNA polymerase I core binding • 激酶活性 • protein C-terminus binding • 血浆蛋白结合 • 相同蛋白质结合 • protein heterodimerization activity • transmembrane receptor protein tyrosine kinase activity • protein tyrosine kinase activity • protein phosphatase binding • ATP结合 • transmembrane signaling receptor activity • phosphatidylinositol-4,5-bisphosphate 3-kinase activity • 酪氨酸激酶受体 细胞组分 • integral component of membrane • 膜 • myelin sheath • receptor complex • 细胞膜 • basolateral plasma membrane • apical plasma membrane • 细胞质的核周区域 • endosome membrane • cytoplasmic vesicle • 细胞核 • 细胞质 • 细胞质基质 • integral component of plasma membrane • basal plasma membrane 生物学过程 • positive regulation of protein phosphorylation • peripheral nervous system development • regulation of transcription, DNA-templated • negative regulation of immature T cell proliferation in thymus • positive regulation of MAP kinase activity • 磷酸化 • transmembrane receptor protein tyrosine kinase signaling pathway • positive regulation of epithelial cell proliferation • cellular response to growth factor stimulus • 伤口愈合 • oligodendrocyte differentiation • regulation of angiogenesis • positive regulation of translation • transcription, DNA-templated • 神经系统的发育 • MAPK cascade • protein phosphorylation • 心脏发育 • cell surface receptor signaling pathway • positive regulation of GTPase activity • positive regulation of cell growth • regulation of microtubule-based process • neuromuscular junction development • regulation of ERK1 and ERK2 cascade • 髓鞘形成 • 自体磷酸化 • phosphatidylinositol 3-kinase signaling • positive regulation of transcription by RNA polymerase I • 细胞增殖 • positive regulation of transcription by RNA polymerase III • motor neuron axon guidance • enzyme linked receptor protein signaling pathway • 信号转导 • positive regulation of cell adhesion • positive regulation of protein targeting to membrane • ERBB2 signaling pathway • phosphatidylinositol phosphate biosynthetic process • positive regulation of gene expression • peptidyl-tyrosine phosphorylation • regulation of cell motility • cellular response to epidermal growth factor stimulus • regulation of transcription by RNA polymerase II • negative regulation of ERBB signaling pathway • positive regulation of protein kinase B signaling • negative regulation of signal transduction • 细胞分化 • negative regulation of apoptotic process • positive regulation of ERK1 and ERK2 cascade • intracellular signal transduction • positive regulation of cell population proliferation • neuron differentiation • positive regulation of MAPK cascade Sources:Amigo / QuickGO
直系同源
物种	人类	小鼠
Entrez	2064	13866
Ensembl	ENSG00000141736	ENSMUSG00000062312
UniProt	P04626	P70424
mRNA​序列	​NM_001005862 ​NM_001289936 ​NM_001289937 ​NM_001289938 ​NM_004448	NM_001003817 ​NM_010152
蛋白序列	NP_001005862 ​NP_001276865 ​NP_001276866 ​NP_001276867 ​NP_004439 ​NP_001369711 ​NP_001369712 ​NP_001369713 ​NP_001369714 ​NP_001369715 ​NP_001369716 ​NP_001369717 ​NP_001369718 ​NP_001369719 ​NP_001369720 ​NP_001369721 ​NP_001369722 ​NP_001369723 ​NP_001369724 ​NP_001369725 ​NP_001369726 ​NP_001369727 ​NP_001369728 ​NP_001369729 ​NP_001369730 ​NP_001369731 ​NP_001369732 ​NP_001369733 ​NP_001369734 ​NP_001369735	NP_001003817
基因位置​（UCSC）	Chr 17: 39.69 – 39.73 Mb	Chr 11: 98.3 – 98.33 Mb
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维基数据
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人类表皮生长因子受体2（英语：human epidermal growth factor receptor 2，缩写为HER2，亦称为Neu、ErbB-2、CD340（分化群340）或p185）是一种由ERBB2基因编码的蛋白质。HER2是表皮生长因子受体（EGFR/ErbB）家族的成员。

功能

HER2是结合在细胞膜表面的受体酪氨酸激酶，参与导致细胞生长和分化的信号转导途径，由原癌基因HER2/neu编码。一般认为HER2是一个孤受体，表皮生长因子家族的配体都不能激活它。但配体结合ErbB受体时可形成二聚体，且HER2可与ErbB家族的其他成员结合成异二聚体。HER2基因是原癌基因，位于人类17号染色体长臂（17q21-q22）。

与癌症的关系

HER-2基因是影响乳癌预后的一个重要因素，大约有25%-30%左右的乳癌患者，受到体内癌细胞HER-2基因过量表现的影响，他们的癌细胞不仅繁殖能力强，对部分化学治疗药物也容易有抗药性，造成病患即使接受手术治疗，癌细胞仍然有较高复发及转移的几率，无法长期存活。

乳癌病患可分为Her-2/neu阳性或Her-2/neu阴性两种截然不同的预后之乳癌。乳癌患者的肿瘤，若HER-2蛋白质出现过量表现，这类的肿瘤生长速度较快且生物行为较为恶性，使得手术后复发率高于其他类型的乳癌。

表皮生长因子受体(EGFR)信号传导级联

针对HER2的药物

罗氏药厂开发的贺癌平（Herceptin）即是以HER2为标靶的药物，对晚期转移性的乳腺癌颇具效用。

1. 重组型人源化单克隆抗体 Trastuzumab (Herceptin®), 是IgG1 monoclonal antibody，可透过结合到乳癌细胞膜上的HER2 receptor的Domain4去抑制下游的hetero- and homodimerization和信号传递。；
2. 完全人源化单克隆抗体 Pertuzumab (Perjeta®)，和Trastuzumab药理作用位点相似，但Pertuzumab 是结合在HER2的Domain2，去抑制下游路径，而且因为Domain2是属于extracellular receptor dimerization，因此可防止其他的HER family members和HER2进行dimerization，从而抑制了ligand-induced signaling，抑制了细胞生长而进行细胞凋亡，其中HER2/HER3被认为是下游通路激活的最强二聚体；
3. 单抗结合型药物 Ado-Trastuzumab emtansine (Kadcyla®)，为新药，是一种Antibody和Drug的conjugate（ADC）。Trastuzumab上述已介绍过他的作用位点，而新药T-DM1则是将Trastuzumab和maytansine 1用thioether键结起来，DM1即derivative of maytansine 1，是一种合成Microtubule 过程中dimerization的抑制剂，将Trastuzumab和cytotoxic agent DM1结合，除了有Trastuzumab本身能够与HER2 receptor Domain4结合，进而停止了癌细胞的生长，DM1透过receptor-mediated进入细胞内作用，并在lysosome内代谢，释放出含DM1的代谢产物，此物质可结合在Microtubule上，导致有丝分裂终止和细胞死亡。
4. Neratinib，为口服制剂，irreversible inhibitor，抑制HER2 and EGFR protein tyrosine kinase(TK)。
5. 酪氨酸激酶抑制剂 Lapatinib Ditosylate (Tykerb®)，口服制剂，和Neratinib相似，一样是EGFR and HER2 tyrosine kinase的抑制剂。
6. mTOR 抑制剂 Everolimus (Afinitor®)

深入阅读

• Ross JS, Fletcher JA, Linette GP; et al. The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist. 2003, 8 (4): 307–25. PMID 12897328. doi:10.1634/theoncologist.8-4-307.  引文格式1维护：显式使用等标签 (link)
• Zhou BP, Hung MC. Dysregulation of cellular signaling by HER2/neu in breast cancer. Semin. Oncol. 2003, 30 (5 Suppl 16): 38–48. PMID 14613025. doi:10.1053/j.seminoncol.2003.08.006. 
• Ménard S, Casalini P, Campiglio M; et al. Role of HER2/neu in tumor progression and therapy. Cell. Mol. Life Sci. 2005, 61 (23): 2965–78. PMID 15583858. doi:10.1007/s00018-004-4277-7.  引文格式1维护：显式使用等标签 (link)
• Becker JC, Muller-Tidow C, Serve H; et al. Role of receptor tyrosine kinases in gastric cancer: new targets for a selective therapy. World J. Gastroenterol. 2006, 12 (21): 3297–305. PMID 16733844.  引文格式1维护：显式使用等标签 (link)
• Laudadio J, Quigley DI, Tubbs R, Wolff DJ. HER2 testing: a review of detection methodologies and their clinical performance. Expert Rev. Mol. Diagn. 2007, 7 (1): 53–64. PMID 17187484. doi:10.1586/14737159.7.1.53. 
• Bianchi F, Tagliabue E, Ménard S, Campiglio M. Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections. Cell Cycle. 2007, 6 (6): 643–6. PMID 17374991. doi:10.4161/cc.6.6.4033. 
• Del Bimbo A., Meoni M., Pala P. Accurate evaluation of HER-2 amplification in FISH images. Imaging Systems and Techniques (IST), 2010 IEEE International Conference on. 2010: 407–10. ISBN 978-1-4244-6492-0. doi:10.1109/IST.2010.5548461. 

外部链接

• ERBB2 expression across human cancerous and healthy tissues
• AACR Cancer Concepts Factsheet on HER2
• Her2/neu Vaccine Protects Against Tumor Growth
• Chimeric molecules and Methods of Use
• Breast Friends for Life Network - A South African Breast Cancer Support Forum for HER2 Positive Women
• 医学主题词表（MeSH）：Receptor,+erbB-2