Recombinant Human Receptor tyrosine-protein kinase erbB-4 (ERBB4), partial

Code CSB-YP624020HU
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Source Yeast
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Code CSB-EP624020HU
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Source E.coli
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Code CSB-EP624020HU-B
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Source E.coli
Conjugate Avi-tag Biotinylated
E. coli biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15 amino acid AviTag peptide. This recombinant protein was biotinylated in vivo by AviTag-BirA technology, which method is BriA catalyzes amide linkage between the biotin and the specific lysine of the AviTag.
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Code CSB-BP624020HU
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Source Baculovirus
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Code CSB-MP624020HU
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Source Mammalian cell
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Product Details

>85% (SDS-PAGE)
Target Names
Uniprot No.
Alternative Names
4ICD; ALS19; Avian erythroblastic leukemia viral oncogene homolog 4; Avian erythroblastic leukemia viral v erb b2 oncogene homolog 4; E4ICD; EC; Erbb4; ERBB4 intracellular domain; ERBB4_HUMAN; HER 4; HER4; human epidermal growth factor receptor 4; Mer4; MGC138404; Oncogene ERBB4; p180erbB4; Proto-oncogene-like protein c-ErbB-4; Receptor protein tyrosine kinase erbB 4 precursor; Receptor tyrosine protein kinase erbB 4; s80HER4; Tyrosine kinase type cell surface receptor HER4; Tyrosine kinase-type cell surface receptor HER4; v erb a avian erythroblastic leukemia viral oncogene homolog like 4; v erb a erythroblastic leukemia viral oncogene homolog 4; v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian); V-ERB-B2 avian erythroblastic leukemia viral oncogene homolog 4; Verba avian erythroblastic leukemia viral oncogene homolog like 4; Verba erythroblastic leukemia viral oncogene homolog 4; VERBB2
Homo sapiens (Human)
Protein Length
Tag Info
The following tags are available.
N-terminal His-tagged
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer before Lyophilization
Tris/PBS-based buffer, 6% Trehalose, pH 8.0
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Please contact us to get it.

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Target Background

Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.
Gene References into Functions
  1. Studied association of two erb-b2 receptor tyrosine kinase 4 (ERBB4) polymorphisms with genetic predisposition of schizophrenia in a Jordanian Arab population. PMID: 28425244
  2. ERBB4 rs1351592 confers risk for polycystic ovary syndrome in Han Chinese. PMID: 28195137
  3. Results found that ERBB4 was highly expressed in gastric cancer cell (GC) lines and tumors and closely related to the poor prognosis of GC patients. Other data indicated that ERBB4 promoted cell proliferation via PI3K/Akt signaling pathway. PMID: 29620274
  4. Study found that the protein levels of NRG1 and ErbB4 were significantly increased in the temporal cortex of patients with symptomatic epilepsy. Also, NRG1-ErbB4 signaling suppresses GluN2B phosphorylation by Src inhibition. GluN2B is closely related to synaptic activity and its regulation by the NRG1-ErbB4-Src signaling axis highlights the importance of NRG1-ErbB4 signaling in symptomatic epilepsy pathology. PMID: 28273943
  5. present study shows that HER4 and/or NDRG1 might play a critical role for the cell survival and chemo-resistance of Osteosarcoma (OS), and could be used as potential therapeutic targets in OS. PMID: 29524631
  6. This study support the involvement of Neuregulin signaling pathway in smoking behavior but not in alcohol use and abuse, and disclose functional potential for 56 of the 66 associated single-nucleotide polymorphism and underlining the involvement of ERBB4 in SI, ND and NW. PMID: 28892072
  7. These finding suggests that miR-302b inhibits key transcription factors and cytokines by targeting ERBB4, IRF2 and CXCR4, implicating its role in the inhibition of CRI in EC. PMID: 28467773
  8. we have exploited the hidden information inside ErbB4 kinase receptor both at sequence and structural level. PSI-BLAST algorithm is used to search similar sequences against ErbB4 kinase sequence. Top 15 sequences with high identity were selected for finding conserved and variable regions among sequences using multiple sequence alignment PMID: 28670936
  9. Receptor protein-tyrosine kinase ErbB-4 (ERBB4) is expressed in the basal layer of human epidermis and cultured keratinocytes as well as in murine epidermis. PMID: 29410073
  10. our study demonstrated and highlighted the strong prognostic value of HER4 in breast cancer carcinoma. The detection of the strong association of cytoplasmic HER4 with RFS might serve as an effective tool for investigating the multifunctionality of HER4 in predicting prognosis and its possible contribution to providing optimal treatment to patients with cancer. PMID: 27736797
  11. In silico analysis suggested that rs1972820 located in the 3'UTR of ERBB4 gene affects the binding affinity of miR-3144-3p a potential oncomiRNA. Statistical analysis showed a significant association between SNP rs1972820 G allele and reduced breast cancer risk, odds ratio = 0.443 (95% CI: 0.196-0.998). PMID: 28508829
  12. conclude from these results that this loss in Intron 1 of the ERBB4 gene is neither a de novo driver mutation nor a predisposing factor to GBM, despite the indications from CCLE PMID: 29342193
  13. findings indicate that a SUMOylation-mediated mechanism regulates nuclear localization and function of the ICD of ErbB4 receptor tyrosine kinase PMID: 28974580
  14. Convergence between EGFR/ErbB4 and canonical/noncanonical Wnt signaling determines cardiogenic fate in human pluripotent stem cells. PMID: 27324647
  15. ERBB4 gene polymorphism is associated with the risk of congestive heart failure and prognosis in Chinese people. PMID: 26844763
  16. High ERBB4 expression is associated with Merkel cell carcinoma PMID: 28359267
  17. High ERBB4 expression is associated with colon cancer metastasis. PMID: 28629469
  18. ERBB4 mutation is associated with Metaplastic Breast Cancer. PMID: 27568101
  19. Results show higher expression levels of ErbB4 and KITENIN in stage IV colorectal cancer tissues resulting in elevated phosphorylated level of ERBB2. PMID: 27648936
  20. review and meta-analysis, does not play essential role in clinicopathology and prognosis of gastric cancer PMID: 27536774
  21. We directly link TDP-43 loss of function toxicity to two genes with rare amyotrophic lateral sclerosis and frontotemporal lobar degeneration-causing mutations, CHMP2B and ErbB4 PMID: 27621269
  22. Parallel microarray profiling identifies Erbb4 as a marker of cyst growth in autosomal dominant polycystic kidney disease and as a prognostic marker for disease progression. PMID: 28077374
  23. the HER4 G1109C mutation is an activating oncogenic mutation with a transformational ability and that afatinib was effective against an HER4 G1109C-mutated HNSCC cell line by inhibiting the HER4 signal, both in vitro and in vivo. PMID: 27207775
  24. identified a novel Her4-induced posttranslational modification on MDMX PMID: 27777309
  25. In this study, we aimed to investigate the association of ERBB4 rs707284 with the risk of Schizophrenia in an Iranian population. There was no association between the risk of Schizophrenia and rs707284. PMID: 28384043
  26. Meta-analysis identified a statistically significant association between ErbB4 SNP rs707284 and susceptibility to schizophrenia among Asian and Caucasian populations under allelic model and marginal associations under recessive and homozygous models. In addition, in Asian subgroup analysis, rs707284 was marginally associated with schizophrenia under the recessive model. PMID: 28225484
  27. Our results indicated that SNP rs11895168 C allele located in ErbB4 3'UTR was significantly associated with elevated breast cancer risk. PMID: 27262100
  28. Advanced bioinformatic analysis softwares were used to analyze the regulatory mechanism after ErbB4 gene mutation in terms of amino acid sequence, primary, secondary, and tertiary structure of the protein and upstream-downstream receptor/ligands. Mutation of the 19th and 113th amino acids at the carboxyl terminus of ErbB4 protein did not affect its biological nature, but its secondary structure changed PMID: 27323039
  29. High ERBB4 Expression is associated with Ovarian Serous Carcinoma Resistant to Platinum-Based Therapy. PMID: 28178720
  30. interaction with rs1836724 C variant within ErbB4 may be associated with higher expression of ESR1 (ERpositive phenotype). PMID: 27035115
  31. haplotypes CAAAI and TAAAD (rs12052398, rs13393577, rs13424871, rs16847082 and rs6147150I) of the ERBB4 polymorphisms are associated with a significantly lower risk of prostate cancer. PMID: 27609473
  32. Results from the expression profile of ERBB4 suggest that it might serve as a prognostic marker in patients with triple negative breast cancer. PMID: 26907936
  33. Genetic variants in ERBB4 is associated with chronic hepatitis B virus infection. PMID: 26701850
  34. The connections of EGFR and ERBB4 signaling with SREBP-2-regulated cholesterol metabolism are likely to be important in ERBB-regulated developmental processes and may contribute to metabolic remodeling in ERBB-driven cancers. PMID: 26535009
  35. nuclear HER4 seem to be co-located with estrogen receptors, however, we did not find support for overall HER4 expression in independently predicting response of tamoxifen treatment in breast cancer PMID: 26238412
  36. the presence of activating driver mutations of ERBB4 in non-small cell lung cancer PMID: 26050618
  37. A combination of miRNAs induced via endothelial coculture improved embryonic-stem-cell-derived cardiomyocytes maturity, in part through suppression of ErbB4 signaling. PMID: 26365191
  38. Identification of a new subclass of ALK-negative Anaplastic large-cell lymphoma characterized by aberrant expression of ERBB4-truncated transcripts carrying intronic 5' untranslated regions. PMID: 26463425
  39. In this study, we developed an anti-ErbB4 mAb (clone P6-1) that suppresses NRG-dependent activation of ErbB4 and examined its effect on breast cancer cell proliferation in the extracellular matrix. PMID: 26780728
  40. Dysregulated ErbB4splicing in schizophreniamay contribute to lower activity of parvalbumin interneurons and an activity-dependent down-regulation of parvalbumin expression. PMID: 26337038
  41. NRG4 and its receptor ErbB4 are present in human breast milk and developing human intestine, respectively. Thus, NRG4-ErbB4 signaling may be a novel pathway for therapeutic intervention or prevention in NEC. PMID: 25216938
  42. Authors investigated the effects of ERBB4 variants and family history of SCZ and/or BPD (FH) on cortical measures and cognitive performances. PMID: 25744101
  43. There are isoform-specific roles of ERBB4 during puberty and early pregnancy. CYT-1 ERBB4a has oncogenic properties. PMID: 25516216
  44. Elevated ERBB4 expression is associated with drug resistance in colorectal cancer. PMID: 24893630
  45. ERBB4 is over-expressed in human colon cancer and enhances cellular transformation. PMID: 25916654
  46. amplification of ERBB4, C-MET and CD44 was significantly associated with certain clinicopathological characteristics, particularly tumor differentiation and cancer-related death and poor survival. PMID: 22606006
  47. identifying neuregulin 1 and its cognate receptor ERBB4 [epidermal growth factor receptor (EGFR) family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4] as a major receptor complex that activates YAP activity PMID: 25492964
  48. These observations connect the unusual nuclear function of a growth factor receptor with a mechanosensory pathway and suggest that NRG1-ERBB4-YAP signaling contributes to the aggressive behavior of tumor cells. PMID: 25492965
  49. A small cluster located in the 5' end of the ERBB4 gene showed a nominal association mainly with negative, general and total dimensions of the Positive and Negative Syndrome Scale. PMID: 25142529
  50. Our data suggested that individuals in Chinese population with the ErbB4 12-bp deletion allele may be at higher risk for CRC, rs6147150 would potentially be a promising novel biomarker for Colorectal cancer susceptibility PMID: 25335735

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Involvement in disease
Amyotrophic lateral sclerosis 19 (ALS19)
Subcellular Location
Cell membrane; Single-pass type I membrane protein. Note=In response to NRG1 treatment, the activated receptor is internalized.; [ERBB4 intracellular domain]: Nucleus. Mitochondrion. 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.
Protein Families
Protein kinase superfamily, Tyr protein kinase family, EGF receptor subfamily
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 e
Database Links

HGNC: 3432

OMIM: 600543

KEGG: hsa:2066

STRING: 9606.ENSP00000342235

UniGene: Hs.390729

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