Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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erb-b2 receptor tyrosine kinase 4(ERBB4) erb-b2 receptor tyrosine kinase 4(ERBB4) Related Genes Homo sapiens
CHROMOSOME 2,
CYTOBAND 2q33.3-q34,
ENSEMBL_GENE_ID ENSG00000178568,
GENERIF_SUMMARY cleavage by gamma-secretase releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus, ErbB4 expression was observed through all stages of chondrocytic differentiation in vitro., deletion of the PDZ domain recognition motif does abrogate the gamma-secretase cleavage of ErbB-4, ErbB4 is specifically associated with neuritic plaques in the hippocampus of Alzheimer disease patients., ErbB4 signaling is growth inhibitory and may be coupled to tumor suppression in prostate cells, Expression of HER4 protein correlates with favourable tumor stage in pancreatic cancer patients., YAP is a potential signaling partner of the full-length ErbB4 receptor at the membrane and of the COOH-terminal fragment of ErbB-4 that translocates to the nucleus to regulate transcription, ErbB-4 characterization of the cleavage site and m80 fragment, Nuclear localization of the activated p80 fragment of Her-4 is associated with osteosarcoma pathogenesis, HER4 is involved in a non-proliferative or even protective role in breast cancer., betacellulin may play a role as a local growth factor in promoting the differentiated villous trophoblastic function via ErbB-1 in early placentas and in contributing to placental growth through EVT cell function via ErbB-4 in term placentas., nuclear localization of STAT5A and stimulation of the beta-casein promoter requires nuclear translocation of the ERBB4 intracellular domain 4ICD; binding of the two proteins at transcription factor target promoters results in activation of gene expression, ErbB4 is increased by cAMP, a potent inducer of decidualization of the endometrial stroma., erbB receptor inactivation by unknown mechanisms results in altered splicing of bcl-x towards enhanced formation of proapoptotic Bcl-xS, thereby contributing to enhanced apoptotic susceptibility of failing human myocardium, Association of ErbB4 expression with clinical outcome is dependent on the subcellular localization of ErbB4 and that a proteinase-cleavable ErbB4 isoform promotes growth of ER-positive breast cancer and enhances ER-mediated gene transcription., proteolytic processing of ERBB4 is a critical event regulating multiple receptor signaling activities, Absence of HER4 expression is associated with recurrence of ductal carcinoma in situ of the breast, HB-EGF may play a vital role in regulating luteal growth in a juxtacrine manner and through activating HER4 signalling, Data show that expression of the ErbB-4 ICD fragment leads to its constitutive association with and tyrosine phosphorylation of Mdm2., WWOX antagonizes the function of YAP by competing for interaction with ErbB-4 and other targets and thus affect its transcriptional activity., the s80 domain of ErbB-4 may function to phosphorylate substrates in the cytoplasm or nucleus, Data suggested that alterations of ERBB4-mediated signaling pathway by ERBB4 mutations may contribute to the development of human cancers., Results report the 2.4 A crystal structure of the extracellular region of human ErbB4 in the absence of ligand and show that it adopts a tethered conformation similar to inactive forms of ErbB1 and ErbB3., Mutation screening of erbB4 in 14 schizophrenics revealed 15 SNPs., novel transforming mechanism for the ErbB4 receptor in human breast cancer that is 1) specific for a single receptor isoform and 2) depends on proteinase cleavage and kinase activity but not ligand activation of the receptor, Results showed a highly significant difference between patient and control groups in three SNPs from one linkage disequilibrium block both in allele and genotype frequencies, as well as a risk haplotype., Activation of Rac by heregulin beta1 is mediated not only by ErbB3 and ErbB2 but also by transactivation of EGFR, and it is independent of ErbB4., A monoclonal antibody to ErbB-4 showed both an inhibitory effect on growth rate and an increasing apoptotic rate in the cells expressing ErbB-4., ErbB4 receptor expression was accompanied with positive regulation of PP2A for phosphorylation of Shc Tyr317 and its downstream ERK phosphorylation in MCF-7 and SK-OV-3 cell lines, but not in LNCaP and PC-3 cells., These experiments demonstrate a novel mechanism controlling ErbB receptor activation. Ras induces ErbB4 receptor phosphorylation in a non-autocrine manner and this activation depends on multiple Ras effector pathways and on ErbB4 kinase activity., Function of HER4 and its fragments is particularly important, with the different functions of nuclear and mitochondrial HER4 in breast cancer., HER3 and HER4 has been related to a favourable prognosis in bladder cancer., ErbB4 has 5 docking sites for Grb2. It is a direct binding partner for STAT5. It functions as control center & integration site for signaling processes, involving stimulation with neuregulin., Neurogulin 1 induced activation of erbB4 in the prefrontal cortex in schizophrenia., Cytosolic but not membrane ERBB4/4ICD expression in primary human breast tumors was associated with tumor apoptosis, providing a mechanistic explanation for the loss of ERBB4 expression during tumor progression., -16 E5 protein can form a complex with ErbB4 via binding to the extracellular and transmembrane domains of ErbB4 (JM-b/CYT-1), Down regulation of ERBB4 is associated with brease, prostate and ovarian cancer, Expression of c-erbB-4 in brain medulloblastoma and its correlation with prognosis., low-level hedgehog signalling in human medulloblastoma is associated with the selective maintenance of high ErbB-4 CYT-1 expression, an alteration that exerts tumor-promoting effects, Contribution of an autocrine ERBB4/estrogen receptor signaling pathway to tumor growth and therapeutic response should be considered when managing patients with ER-positive breast cancer., These results suggest that heregulin-mediated growth inhibition in HER4-postive breast cancer cells requires BRCA1., phosphorylation of ErbB4 tyrosine 1056 is critical for coupling ErbB4 to prostate tumor suppression, Data show that upon neuregulin-induced activation and presenilin-dependent cleavage of ErbB4, the receptor's intracellular domain forms a complex with TAB2 and the corepressor N-CoR., Dysregulation of splice-variant specific expression of ErbB4 in the brain underlies the genetic association of the gene with schizophrenia., Inhibits mammary cell proliferation through the action of its cytoplasmic domain., cycle-dependent degradation of s80(HER4) limits its growth-inhibitory action, and stabilization of s80(HER4) enhances tumor suppression, thus providing a link between HER4-mediated growth inhibition and cell cycle control, study concludes that erbB4 mutations are rare in Japanese people with lung cancer, ErbB4 isoform that is proteinase cleavable but does not contain a PI3K-binding domain in its cytoplasmic tail, mediates important functions in renal epithelial cells in response to HB-EGF, Expression of Wwox is associated with ErbB4 expression and that their coexpression has prognostic significance in breast cancer., Gln43 of NRG2beta is both necessary and sufficient for NRG2 stimulation of ErbB4 coupling to IL3 independence., ErbB3 and ErbB4 genes play different roles in carcinogenesis and development, and relate to the reccurrence of carcinoma., The ERBB4 -782 G>T polymorphism, by virtue of its in vitro functional implication and incidence, is a risk factor for breast and colorectal cancer., HER4 amplification showed a positive trend in overall and disease-free survival., All ErbB4 residues contacted by lapatinib are conserved in the EGF receptor and HER2/ErbB2, which lapatinib also targets., Ras activation dynamics is dominated by heterodimer-mediated signaling coordination with a large initial speed of dimerization when the concentration of the ErbB4 receptor is considerably high, Her 4 expression showed significantly decreased expression in differentiated throid cancer and correlated with lower T stage, The restriction of robust SVZ ErbB4 expression to neonate and infant age groups may indicate that SVZ-derived ErbB4-dependent postnatal neuronal development is most extensive within a narrow time frame early after birth., our results suggest that variations of the ErbB4 genotype may confer risk for schizophrenia illness via its impact on left frontotemporal connectivity in human brain., several previously unrecognized interactions led to the finding that ErbB4 can recruit and activate STAT1; at a systems level, ErbB4 is much more selective than the other ErbB receptors, ErbB4 expression and signaling are key elements for TNF responses in vivo and in cell culture, protecting intestinal epithelial cells from apoptosis in the inflammatory environment., HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer, results suggest that ErbB4 processing and function may be altered in brain tumours, such as medulloblastoma and pilocytic astrocytoma, via differential expression of juxtamembrane transcript variants., selective loss-of-function mutations of ErbB4 failed to phosphorylate STAT5 and suppressed differentiation of mammary carcinoma., The biological function and clinical implications of HRG, HER-3 and HER-4 in breast cancers negative/low expression of HER-2 remain unclear, Removal of cell surface heparan sulfate increased TACE activity and cleavage of ErbB4 receptor., Poor downregulation of ErbB4 receptors is not due to sequence variations in the Proto-Oncogene Proteins Cbl binding site of these receptors., expression of ErbB3 and ErbB4 may identify a colorectal cancer subgroup with stage II and III colorectal cancer at higher risk of recurrence, estrogen receptor splice variant and ErbB4 may have roles in gene susceptibility pathways in schizophrenia, Results showed that 45.8% of typical carcinoid and 28.6% of atypical carcinoid tumors express EGFR, 100% of the tumors lack expression of ErbB2, and 100% have moderate to intense staining for ErbB3 and ErbB4., Current data relating to the prognostic significance of HER3 and 4 receptors, as well as their impact on the activity of HER-targeting therapies in patients with breast cancer., WWP1 and its family members suppress the ErbB4 expression and function in breast cancer, The Cyt1 and Cyt2 ErbB4 isoforms, differing by only 16 amino acids, exhibit markedly opposing effects on mammary epithelium growth and differentiation., Data show that aberrant expression of ErbB2, ErbB3 and ErbB4 in the two resistant cell lines, suggesting the existence of an autocrine loop leading to constitutive activation of MAPK and PI3K/Akt survival pathways., Both HER4 expression and HER4 gene amplification emerged as independent prognostic markers in Herceptin-treated breast cancer patients and responsiveness to Herceptin turned out to be more efficient if tumour cells show HER4 expression., Melanoma cells expressing mutant ERBB4 had reduced cell growth after shRNA-mediated knockdown of ERBB4, Results suggest that the HER4 intracellular cytosolic domain 4ICD has important pathological functions and may be used to identify node-negative breast cancer patients at low risk of relapse and an improved survival., Data demonstrate that sequence differences on the C-lobe surface influence the heterodimerization and activation of ErbB2/4 kinase domains., EGFR, HER-2 and HER-4 expression is not associated with poorer survival in neuroendocrine cancer, Data suggest that pulmonary ErbB4 deletion results in a structural and functional delay in fetal lung development, indicating a crucial regulatory role of ErbB4 in the timely progression of fetal lung development., The HER4 intracellular domain is a physiologically important ERalpha coactivator and cooperates with ERalpha to potentiate PgR expression in the normal and malignant breast., chronic overexpression of ErbB4 in the context of inflammation could contribute to colitis-associated tumorigenesis by inhibiting colonocyte apoptosis, The result of this study supported the involvement of the ERBB4 gene in schizophrenia in Han Chinese in Taiwan.., verified HER4 promoter methylation in primary breast carcinomas and detected a significant increase in HER4 promoter methylation in HER4-negative breast tumors, Novel splice variants of ErbB4 exist in the developing and adult human brain., We observed epistasis between NRG1 (rs10503929; Thr286/289/294Met) and its receptor ERBB4 (rs1026882; likelihood ratio test P = .035); a 3-way interaction with these 2 SNPs and AKT1 (rs2494734) was also observed., ERBB4 mutations and expression was not associated with lung cancer., HER receptor family plays an important role in embryonic development and in pathogenesis and progression of neuroblastic tumors., Data show that interactions between beta1 integrin and ErbB4 occur in a spatiotemporally-regulated manner, and such interaction contributes to the integrin-dependent cell migration., this study found that genetic variation at the rs4673628 locus in the ErbB4 gene was significantly associated with anterior limb of the internal capsule white matter. integrity which was also significantly and positively associated with mnemonic function, data indicate that somatic point mutation of ERBB4 gene is rare in common solid cancers except malignant melanoma; also, they suggest that ERBB4 mutation may play roles in limited types of human cancers, Association of common variants in ERBB4 with congenital left ventricular outflow tract obstruction defects., 148 Penile squamous cell carcinoma were microarrayed and immunostained for phosphorylated EGFR (pEGFR), HER2, HER3, HER4, phosphorylated Akt (pAkt), Akt1 and PTEN proteins., the kinase-domain makes a significant contribution to the overall dimerization affinity of the full-length Her4 protein, Letter, A modestly associated novel variant that could affect alternative splicing of ERBB4, was found.., data provide evidence for conserved expression patterns of ErbB4 across different rodent and primate species, both at the cellular and subcellular level., The HER4 is expressed in lymphoma cells, especially in MALT and FL cells of the gastrointestinal tract., ErbB4 rs7598440 genotype significantly predicts cortical GABA concentration, with (A) adenosine allele carriers having higher GABA as predicted by allelic impact on ErbB4 expression., No significant association between ErbB4 and bipolar affective disorder, major depressive disorder and schizophrenia is found in the Han Chinese population., Report here the 2.5 A crystal structure of the N-terminal three extracellular domains of ErbB4, which bind ligand but lack domain IV and thus the tether contact., Verbal working memory performance was associated with 2 variants of ERBB4. No associations were detected between ERBB4 variants and trait schizotypy. rs7598440 was associated with psychotic experiences expressed under stressful environmental conditions., Data suggest that the rs6147150 polymorphism of ErbB4 may be associated with hepatocellular carcinoma (HCC) risk, in part through let-7c-mediated regulation, and may be involved in the pathogenesis of HCC in Chinese populations., soluble ErbB4 intracellular domain promotes HIF-1alpha stability and signaling via a novel mechanism., Immunoreactivity for erbB1 was strong and that for erbB2 and 3 was moderate, while that for erbB4 was faint in nasal mucosa chronic rhinitis., ErbB4 mutant mice exhibit hyperactivity in a novel environment and deficits in prepulse inhibition of the startle response., current results indicated that HER4 protects NBL cells from multiple exogenous apoptotic stimuli, including anoikis, nutrient deficiency, and cytotoxic chemotherapy., A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34 in Korean women., Transgenic mouse embryos lacking ErbB4 display deficits in early oligodendrocyte precursor cell migration away from different oligodendrogliogenic regions., The A-allele of rs7598440 in ERBB4 is associated with increased gamma-aminobutyric acid (GABA) concentrations in the central nervous system., This study revealed that the previously described up-regulation of EGFR and down-regulation of ERBB4 occurred in all analyzed renal cell carcinoma types, whereas down-regulation of ERBB2 and LRIG1 was only present in clear cell renal cell carcinoma., PIAS3 is a novel regulator of ErbB4 receptor tyrosine kinase, controlling its nuclear sequestration and function., amplification of ERBB4, C-MET and CD44 was significantly associated with certain clinicopathological characteristics, particularly tumor differentiation and cancer-related death and poor survival., Although statistically not significant, the tendency towards associations between ERBB4 polymorphisms and the risk of schizophrenia and SPEM abnormality in this study from a Korean population would be helpful for further genetic studies in schizophrenia., We report cell-based assays that provide evidence for active, singly ligated dimers of human EGFR and its homolog, ErbB4/HER4., This effect was blocked by the inhibition of ErbB4, a key NRG1 receptor., ErbB4 processing is enhanced in breast cancer tissue in vivo, HER4 expression was not associated with prognostic factors in ER-positive breast cancer., We observed the reaction kinetics between fluorescently labeled single HRG molecules and ErbB3/B4 on the surfaces of MCF-7 human breast cancer cells., Low ErbB4 expression is associated with metastasis in breast cancer., Rate of ErbB4 expression in remaining nigral dopaminergic neurons increases in Parkinson disease., Results suggest a possible participation of erbB1-4 and claudin-1 in tissue remodelling in chronic hypertrophic rhinitis., Thus, our findings reveal c-Src-mediated inhibitory regulation of ErbB4 nuclear signaling upon EGFR activation., The study indicates that hotspot mutations in the ERBB4 gene are rare in Chinese patients with melanomas., identified a novel 6-kb haplotype block in ERBB4 which was significantly associated with risk of developing schizophrenia Caucasians, total ErbB4 protein expression was not significantly associated with prognostic markers, The present data suggest that ErbB2, ErbB3, and ErbB4 genes may have a role in bladder cancer tumorigenesis., There is no enrichment of ERBB4 mutations BRAF/INRAS mutant melanoma cells., Data suggest that ErbB receptors (ERBB2, ERBB3, and ERBB4) are expressed in most endometrial cancers; expression of ErbB receptors appears to be related to poor prognosis; dismal outcomes correlate with cancers positive for all three ErbB receptors., No cross-reactivity of 4B5 with membrane-bound HER4 was identified in the clinical IHC analysis of formalin-fixed paraffin-embedded breast carcinoma cases as evidenced by the HER4 antibody clone E200., The association of SNP loci derived from GWAS in European type 1 diabetes with diabetic nephropathy was not replicated in the Japanese patients with type 2 diabetes, although the ERBB4 locus may have some effect also in Japanese type 2 diabetes., ERBB4 expression is elevated in metastatic tumour samples and correlates with disease progression in Ewing sarcoma., Data indicate that Lrig3 opposes Lrig1 negative regulatory action and enhances ErbB receptors ERBB2, ERBB3 and ERBB4 stability., Data provide evidence for the involvement of intron 1 EGFR variants and intron 24 ERBB4 variants in modulating risk for the development of in situ and invasive cervical cancer., In tumours from postmenopausal women harbouring normal HER2 gene copy numbers, we found HER2 and HER4, but HER3 levels in particular, to be elevated compared to normal tissues, these data suggest that Nrg3/ErbB4 signaling may be an important factor in nicotine dependence., Expression of HER4 JM-a/CYT2 isoform relate to survival of bladder cancer patients only if the tumors do not express ESR1., our study reveals a positive impact of Her4 (JM-a) expression in triple-negative (OS) and Her2/ER-positive (EFS) breast cancer., reduced autophosphorylation of ErbB4 upon NRG-1 stimulation is involved in the pathogenesis of amyotrophic lateral sclerosis, Data suggest that WW2 domain of WWOX (WW domain containing oxidoreductase protein) augments binding of WW1 domain of WWOX to PPXY motifs within intracellular domain of ErbB4, implying that WW2 serves as chaperone within WW1-WW2 tandem module of WWOX., Studied molecular and network models of HER4/ErbB4 activation and signaling in order to elucidate molecular mechanisms of activation and rationalize the effects of the clinically identified HER4 somatic mutants., In summary, we demonstrate for the first time that a cell surface receptor functions as an obligate ER coactivator with functional specificity associated with breast tumor cell proliferation and cell cycle progression., these results support a cooperation of ErbB1, ErbB4, and members of the MMP family in predicting OSCC invasion and poor clinical outcomes., Results further emphasize the role of HER4 as an important oncogene in malignant melanoma., MiR-302b is a potential molecular marker of esophageal squamous cell carcinoma and functions as a tumor suppressor by post-transcriptionally regulating ErbB4., discovered that ERBB4 and S6K2 were the direct targets of miR-193a-3p and that PIK3R3 and mTOR were the direct targets of miR-193a-5p in non-small-cell lung cancer, This study provide evidence from this independent Australian postmortem cohort that ErbB4-JMa expression is elevated in schizophrenia., The diverse biologic activities of ERBB4 isoforms., Study addresses whether the ERBB3 mutations altering Val-104 were present in homologous amino acids of ERBB family genes EGFR, ERBB2 and ERBB4 in CRC., Elevated ERBB4 expression is associated with drug resistance in colorectal cancer., ErbB3, ErbB4, and MET showed marked expression in 76%, 98%, and 96% of ovarian carcinoma cases., Data shows that HER4 expression status allows stratification of Cholangiocarcinoma patients into different survival categories., In 238 primary invasive breast cancer patients, authors analyzed the expression levels of HER4 extracellular (JM-a and JM-b) and intracellular (CYT-1 and CYT-2) domains, germ-line ERBB4 variant -815A>T as a novel prognostic marker in high-risk early breast cancer, An exon array analysis of 155 breast tumors revealed that the relative mRNA abundance of the ErbB4 CYT2 variant was increased in ER+ HER2- breast cancer patients, 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., 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., 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, Taken together, our findings provide the first clues regarding the role of miR-193a-3p as a tumor suppressor in lung cancer through the inhibition of ERBB4 translation., Phosphorylated ErbB1-4 and heregulin contribute to poorer patient prognosis in CRC. This heregulin-ErbB family member autocrine loop may be a candidate for targeted treatment of CRC., analysis of activator-receiver preferences among ErbB proteins, 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, 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., There are isoform-specific roles of ERBB4 during puberty and early pregnancy. CYT-1 ERBB4a has oncogenic properties., Report high expression of HER2 in gastric adenocarcinomas., EGFR/ERBB4 expression in trophoblasts correlates with cell cycle progression and hyperplasia in complete hydatidiform moles, Authors investigated the effects of ERBB4 variants and family history of SCZ and/or BPD (FH) on cortical measures and cognitive performances., ERBB4 is over-expressed in human colon cancer and enhances cellular transformation., The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer., the presence of activating driver mutations of ERBB4 in non-small cell lung cancer, 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, Dysregulated ErbB4splicing in schizophreniamay contribute to lower activity of parvalbumin interneurons and an activity-dependent down-regulation of parvalbumin expression., A combination of miRNAs induced via endothelial coculture improved embryonic-stem-cell-derived cardiomyocytes maturity, in part through suppression of ErbB4 signaling., 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., 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., NRG1 promotes the proliferation and migration of coronary artery smooth muscle cells by enhancing the phosphorylation of ErbB2, ErbB3 and ErbB4., 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., while transcript and protein levels of EGFR and ErbB2 were up-regulated or unaffected, respectively, hepatitis c virus induced a substantial reduction of ErbB3 and ErbB4 expression., HER Family Protein Expression in a Greek Population with Gastric Cancer. A Retrospective Hellenic Cooperative Oncology Group Study,
OFFICIAL_GENE_SYMBOL ERBB4,
OMIM_DISEASE Amyotrophic lateral sclerosis 19,
SP_COMMENT catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate., domain:The WW-binding motifs mediate interaction with WWOX., function: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., PTM:Isoform JM-A is processed but not isoform JM-B. So, they respectively represent cleavable and non-cleavable forms of the receptor., PTM:Ligand-binding increases phosphorylation on tyrosine residues., similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily., similarity:Contains 1 protein kinase domain., subunit:Homodimer or heterodimer with each of the other ERBB receptors (Potential). Interacts with PDZ domains of DLG2, DLG3, DLG4 and the syntrophin SNTB2. Interacts with CBFA2T3, MUC1 and WWOX., 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 and isoform JM-B are expressed in cerebellum, but only the isoform JM-B is expressed in the heart.,