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Key Specifications Table
| Species Reactivity | Key Applications | Host | Format | Antibody Type |
|---|---|---|---|---|
| H, M, R | WB, IP, IH(P) | M | Purified | Monoclonal Antibody |
| Description | |
|---|---|
| Catalogue Number | 05-1133 |
| Replaces | 04-348 |
| Description | Anti-erbB4 Antibody, clone HFR1/2G4 |
| Background Information | v-ErbB was identified as the viral counterpart of the EGF Receptor, and its relatives have adopted this nomenclature (or the HER nomenclature for human proteins). These proteins are activated by Heregulin, Neuregulin and Amphiregulin. ErbB-2/HER-2, also known as neu, is amplified in large numbers of highly aggressive breast cancers, but all the family members are capable of heterodimerization, and together activate downstream signaling pathways. ErbB-3 has a natural "substitution" at the codon which is an invariant Lys residue at the ATP-binding site of all protein kinases. It is therefore inactive as a kinase, and can only become phosphorylated by heterodimerization with another erbB-family member. All members of this family, when Tyr-phosphorylated, can nucleate the formation of signaling complexes through adapter proteins. |
| Product Information | |
|---|---|
| Format | Purified |
| Control |
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| Presentation | Purified mouse monoclonal IgM in 0.02 M PB with 0.25 M NaCl, pH 7.6, 0.01% Sodium Azide. |
| Quality Level | MQ100 |
| Applications | |
|---|---|
| Application | Detect erbB4 using this Anti-erbB4 Antibody, clone HFR1/2G4 validated for use in WB, IP, IH(P). |
| Key Applications |
|
| Application Notes | Immunoprecipitation: A previous lot of this antibody was used in IP. Immunohistochemistry: Effective for formalin-fixed, paraffin-embedded sections. Optimal working dilutions must be determined by end user. Immunohistochemistry(paraffin): Representative testing from a previous lot. Optimal Staining of erbB-4/HER-4 Monoclonal Antibody: DCIS and Pancreatic Cancer |
| Biological Information | |
|---|---|
| Immunogen | Synthetic peptide sequence RSTLQHPDYLQEYST from the cytoplasmic domain of the protein, residues 1250-1264. |
| Epitope | Cytoplasmic domain of the protein, residues 1250-1264. |
| Clone | HFR1/2G4 |
| Concentration | Please refer to the Certificate of Analysis for the lot-specific concentration. |
| Host | Mouse |
| Specificity | Reactive with human c-erB-4/Her 4 cytoplasmic domain of the protein (residues 1250-1264), a member of the EGF receptor (type 1) family involved in cell growth regulation. Expression or function may be altered in human cancers. |
| Isotype | IgG1κ |
| Species Reactivity |
|
| Species Reactivity Note | Human and Rat. Expected to react with mouse based on sequence homology. |
| Antibody Type | Monoclonal Antibody |
| Entrez Gene Number |
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| Entrez Gene Summary | This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]. |
| Gene Symbol |
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| Purification Method | Purified |
| UniProt Number |
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| UniProt Summary | FUNCTION: Specifically binds and is activated by neuregulins, including NRG2 and NRG3, HBEGF, BTC and NTAK. Interaction with these factors induces cell differentiation. Plays a role in the regulation of cell growth and cell proliferation. Not activated by EGF, TGF-A, and AREGAREGB. The C-terminal fragment (CTF) of isoform JMA-A CYT-2 (containing E4ICD2) can stimulate transcription in the presence of YAP1. 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. SIZE: 1308 amino acids; 146808 Da SUBUNIT: Homodimer or heterodimer with another ERBB family member (By similarity). Interacts with CBFA2T3 (By similarity). Interacts with DLG2 (via its PDZ domain), DLG3 (via its PDZ domain), DLG4 (via its PDZ domain) and SNTB2 (via its PDZ domain). Interacts with MUC1. Interacts (via its PPxy motifs) with WWOX. Interacts (via the PPxY motif 3 of isoform JM-A CYT-2) with YAP1 (via the WW domain 1 of isoform 1). Interacts (isoform JM-A CYT-1 and isoform JM-B CYT-1) with WWP1. Interacts (via its intracellular domain) with TRIM28. Interacts (via the intracellular domains of both CYT-1 and CYT-2 isoforms) with KAP1; the interaction does not phosphorylate KAP1 but represses ERBB4-mediated transcriptional activity. Interacts with PRPU, DDX23, MATR3, RBM15, ILF3, KAP1, U5S1, U2SURP, ITCH, HNRPU, AP2A1, NULC, LEO1, WWP2, IGHG1, HXK1, GRB7 AND ARS2. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. ERBB4 intracellular domain: Nucleus. Note: 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. TISSUE SPECIFICITY: 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. PTM: 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. Autophosphorylated on tyrosine residues in response to ligand binding. 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 proteasomal 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. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. Contains 1 protein kinase domain. |
| Molecular Weight | ~147 kDa |
| Product Usage Statements | |
|---|---|
| Quality Assurance | Routinely evaluated by Western Blot on A431 lysates. Western Blot Analysis: 1:500 dilution of this lot detected C-ERB-4 on 10 μg of A431 lysates. |
| Usage Statement |
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| Storage and Shipping Information | |
|---|---|
| Storage Conditions | Stable refrigerated at 2-8°C in undiluted aliquots for up to 1 year from date of receipt. |
| Packaging Information | |
|---|---|
| Material Size | 100 µg |