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功能
Specifically binds and is activated by neuregulins, NRG-2, NRG-3, heparin-binding EGF-like growth factor, betacellulin and NTAK. Interaction with these factors induces cell differentiation. Not activated by EGF, TGF-A, and amphiregulin. The C-terminal fragment (CTF) of isoform JMA-A CYT-2 (containing E4ICD2) can stimulate transcription in the presence of YAP1. ERBB4 intracellular domain is involved in the regulation of cell growth. Conflicting reports are likely due at least in part to the opposing effects of the isoform-specific and nuclear-translocated ERBB4 intracellular domains (E4ICD1 and E4ICD2). Overexpression studies in epithelium show growth inhibition using E4ICD1 and increased proliferation using E4ICD2. E4ICD2 has greater in vitro kinase activity than E4ICD1. The kinase activity is required for the nuclear translocation of E4ICD2.
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组织特异性
Expressed at highest levels in brain, heart, kidney, in addition to skeletal muscle, parathyroid, cerebellum, pituitary, spleen, testis and breast. Lower levels in thymus, lung, salivary gland, and pancreas. Isoform JM-A CYT-1 and isoform JM-B CYT-1 are expressed in cerebellum, but only the isoform JM-B is expressed in the heart.
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序列相似性
Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
Contains 1 protein kinase domain.
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翻译后修饰
Isoform JM-A CYT-1 and isoform JM-A CYT-2 but not isoform JM-B CYT-1 and isoform JM-B CYT-2 are processed by ADAM17. Proteolytic processing in response to ligand or 12-O-tetradecanoylphorbol-13-acetate stimulation results in the production of 120 kDa soluble receptor forms and intermediate membrane-anchored 80 kDa fragments (m80HER4), which are further processed by a presenilin-dependent gamma-secretase to release the respective cytoplasmic intracellular domain E4ICD (either E4ICD1/s80Cyt1 or E4ICD2/s80Cyt2). Membrane-anchored 80 kDa fragments of the processed isoform JM-A CYT-1 are more readily degraded by the proteasome than fragments of isoform JM-A CYT-2 suggesting a prevalence of E4ICD2 over E4ICD1.
Ligand-binding increases phosphorylation on tyrosine residues. Isoform JM-A CYT-2 is constitutively phosphorylated on tyrosine residues in a ligand-independent manner. E4ICD2 but not E4ICD1 is phosphorylated on tyrosine residues.
Ubiquitinated. The ERBB4 intracellular domain is ubiquitinated and targeted to proteosomal degradation during mitosis mediated by the APC/C complex. Isoform JM-A CYT-1 and isoform JM-B CYT-1 are ubiquitinated by WWP1. The ERBB4 intracellular domain (E4ICD1) is ubiquitinated, and this involves NEDD4.
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细胞定位
Membrane and Nucleus. Following proteolytical processing E4ICD (E4ICD1 or E4ICD2 generated from the respective isoforms) is translocated to the nucleus. Significantly more E4ICD2 than E4ICD1 is found in the nucleus. E4ICD2 colocalizes with YAP1 in the nucleus.
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Information by UniProt
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数据库链接
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别名
- 4ICD antibody
- ALS19 antibody
- Avian erythroblastic leukemia viral oncogene homolog 4 antibody
- Avian erythroblastic leukemia viral v erb b2 oncogene homolog 4 antibody
- E4ICD antibody
- EC 2.7.10.1 antibody
- Erbb4 antibody
- ERBB4 intracellular domain antibody
- ERBB4_HUMAN antibody
- HER 4 antibody
- HER4 antibody
- human epidermal growth factor receptor 4 antibody
- Mer4 antibody
- MGC138404 antibody
- Oncogene ERBB4 antibody
- p180erbB4 antibody
- Proto-oncogene-like protein c-ErbB-4 antibody
- Receptor protein tyrosine kinase erbB 4 precursor antibody
- Receptor tyrosine protein kinase erbB 4 antibody
- s80HER4 antibody
- Tyrosine kinase type cell surface receptor HER4 antibody
- Tyrosine kinase-type cell surface receptor HER4 antibody
- v erb a avian erythroblastic leukemia viral oncogene homolog like 4 antibody
- v erb a erythroblastic leukemia viral oncogene homolog 4 antibody
- v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) antibody
- V-ERB-B2 avian erythroblastic leukemia viral oncogene homolog 4 antibody
- Verba avian erythroblastic leukemia viral oncogene homolog like 4 antibody
- Verba erythroblastic leukemia viral oncogene homolog 4 antibody
- VERBB2 antibody
see all