Receptor tyrosine-protein kinase erbB-4
Details
- Name
- Receptor tyrosine-protein kinase erbB-4
- Synonyms
- 2.7.10.1
- HER4
- p180erbB4
- Proto-oncogene-like protein c-ErbB-4
- Tyrosine kinase-type cell surface receptor HER4
- Gene Name
- ERBB4
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0008621|Receptor tyrosine-protein kinase erbB-4 MKPATGLWVWVSLLVAAGTVQPSDSQSVCAGTENKLSSLSDLEQQYRALRKYYENCEVVM GNLEITSIEHNRDLSFLRSVREVTGYVLVALNQFRYLPLENLRIIRGTKLYEDRYALAIF LNYRKDGNFGLQELGLKNLTEILNGGVYVDQNKFLCYADTIHWQDIVRNPWPSNLTLVST NGSSGCGRCHKSCTGRCWGPTENHCQTLTRTVCAEQCDGRCYGPYVSDCCHRECAGGCSG PKDTDCFACMNFNDSGACVTQCPQTFVYNPTTFQLEHNFNAKYTYGAFCVKKCPHNFVVD SSSCVRACPSSKMEVEENGIKMCKPCTDICPKACDGIGTGSLMSAQTVDSSNIDKFINCT KINGNLIFLVTGIHGDPYNAIEAIDPEKLNVFRTVREITGFLNIQSWPPNMTDFSVFSNL VTIGGRVLYSGLSLLILKQQGITSLQFQSLKEISAGNIYITDNSNLCYYHTINWTTLFST INQRIVIRDNRKAENCTAEGMVCNHLCSSDGCWGPGPDQCLSCRRFSRGRICIESCNLYD GEFREFENGSICVECDPQCEKMEDGLLTCHGPGPDNCTKCSHFKDGPNCVEKCPDGLQGA NSFIFKYADPDRECHPCHPNCTQGCNGPTSHDCIYYPWTGHSTLPQHARTPLIAAGVIGG LFILVIVGLTFAVYVRRKSIKKKRALRRFLETELVEPLTPSGTAPNQAQLRILKETELKR VKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHL VRLLGVCLSPTIQLVTQLMPHGCLLEYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLV HRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNADGGKMPIKWMALECIHYRKFTHQ SDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYMVMVKCWMID ADSRPKFKELAAEFSRMARDPQRYLVIQGDDRMKLPSPNDSKFFQNLLDEEDLEDMMDAE EYLVPQAFNIPPPIYTSRARIDSNRSEIGHSPPPAYTPMSGNQFVYRDGGFAAEQGVSVP YRAPTSTIPEAPVAQGATAEIFDDSCCNGTLRKPVAPHVQEDSSTQRYSADPTVFAPERS PRGELDEEGYMTPMRDKPKQEYLNPVEENPFVSRRKNGDLQALDNPEYHNASNGPPKAED EYVNEPLYLNTFANTLGKAEYLKNNILSMPEKAKKAFDNPDYWNHSLPPRSTLQHPDYLQ EYSTKYFYKQNGRIRPIVAENPEYLSEFSLKPGTVLPPPPYRHRNTVV
- Number of residues
- 1308
- Molecular Weight
- 146806.865
- Theoretical pI
- Not Available
- GO Classification
- FunctionsATP binding / epidermal growth factor receptor binding / protein homodimerization activity / protein tyrosine kinase activity / receptor signaling protein tyrosine kinase activity / transcription regulatory region DNA binding / transmembrane receptor protein tyrosine kinase activityProcessesactivation of MAPKK activity / axon guidance / cardiac muscle tissue regeneration / cell fate commitment / cell migration / cell proliferation / central nervous system morphogenesis / embryonic pattern specification / epidermal growth factor receptor signaling pathway / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / heart development / innate immune response / insulin receptor signaling pathway / lactation / mammary gland alveolus development / mammary gland epithelial cell differentiation / MAPK cascade / mitochondrial fragmentation involved in apoptotic process / negative regulation of apoptotic process / negative regulation of cell proliferation / negative regulation of neuron migration / nervous system development / neural crest cell migration / neurotrophin TRK receptor signaling pathway / olfactory bulb interneuron differentiation / peptidyl-tyrosine phosphorylation / phosphatidylinositol-mediated signaling / positive regulation of cardiac muscle cell proliferation / positive regulation of cell proliferation / positive regulation of ERK1 and ERK2 cascade / positive regulation of phosphatidylinositol 3-kinase activity / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of protein localization to cell surface / positive regulation of protein phosphorylation / positive regulation of STAT protein import into nucleus / positive regulation of transcription, DNA-templated / positive regulation of tyrosine phosphorylation of Stat5 protein / protein autophosphorylation / Ras protein signal transduction / regulation of cell migration / signal transduction / small GTPase mediated signal transduction / transcription, DNA-templated / transmembrane receptor protein tyrosine kinase signaling pathway / vascular endothelial growth factor receptor signaling pathwayComponentsbasolateral plasma membrane / cytosol / extracellular region / integral component of membrane / mitochondrial matrix / mitochondrion / nucleoplasm / nucleus / plasma membrane / receptor complex
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- 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.
- Pfam Domain Function
- Transmembrane Regions
- 652-675
- Cellular Location
- Cell membrane
- Gene sequence
>lcl|BSEQ0021412|Receptor tyrosine-protein kinase erbB-4 (ERBB4) ATGAAGCCGGCGACAGGACTTTGGGTCTGGGTGAGCCTTCTCGTGGCGGCGGGGACCGTC CAGCCCAGCGATTCTCAGTCAGTGTGTGCAGGAACGGAGAATAAACTGAGCTCTCTCTCT GACCTGGAACAGCAGTACCGAGCCTTGCGCAAGTACTATGAAAACTGTGAGGTTGTCATG GGCAACCTGGAGATAACCAGCATTGAGCACAACCGGGACCTCTCCTTCCTGCGGTCTGTT CGAGAAGTCACAGGCTACGTGTTAGTGGCTCTTAATCAGTTTCGTTACCTGCCTCTGGAG AATTTACGCATTATTCGTGGGACAAAACTTTATGAGGATCGATATGCCTTGGCAATATTT TTAAACTACAGAAAAGATGGAAACTTTGGACTTCAAGAACTTGGATTAAAGAACTTGACA GAAATCCTAAATGGTGGAGTCTATGTAGACCAGAACAAATTCCTTTGTTATGCAGACACC ATTCATTGGCAAGATATTGTTCGGAACCCATGGCCTTCCAACTTGACTCTTGTGTCAACA AATGGTAGTTCAGGATGTGGACGTTGCCATAAGTCCTGTACTGGCCGTTGCTGGGGACCC ACAGAAAATCATTGCCAGACTTTGACAAGGACGGTGTGTGCAGAACAATGTGACGGCAGA TGCTACGGACCTTACGTCAGTGACTGCTGCCATCGAGAATGTGCTGGAGGCTGCTCAGGA CCTAAGGACACAGACTGCTTTGCCTGCATGAATTTCAATGACAGTGGAGCATGTGTTACT CAGTGTCCCCAAACCTTTGTCTACAATCCAACCACCTTTCAACTGGAGCACAATTTCAAT GCAAAGTACACATATGGAGCATTCTGTGTCAAGAAATGTCCACATAACTTTGTGGTAGAT TCCAGTTCTTGTGTGCGTGCCTGCCCTAGTTCCAAGATGGAAGTAGAAGAAAATGGGATT AAAATGTGTAAACCTTGCACTGACATTTGCCCAAAAGCTTGTGATGGCATTGGCACAGGA TCATTGATGTCAGCTCAGACTGTGGATTCCAGTAACATTGACAAATTCATAAACTGTACC AAGATCAATGGGAATTTGATCTTTCTAGTCACTGGTATTCATGGGGACCCTTACAATGCA ATTGAAGCCATAGACCCAGAGAAACTGAACGTCTTTCGGACAGTCAGAGAGATAACAGGT TTCCTGAACATACAGTCATGGCCACCAAACATGACTGACTTCAGTGTTTTTTCTAACCTG GTGACCATTGGTGGAAGAGTACTCTATAGTGGCCTGTCCTTGCTTATCCTCAAGCAACAG GGCATCACCTCTCTACAGTTCCAGTCCCTGAAGGAAATCAGCGCAGGAAACATCTATATT ACTGACAACAGCAACCTGTGTTATTATCATACCATTAACTGGACAACACTCTTCAGCACA ATCAACCAGAGAATAGTAATCCGGGACAACAGAAAAGCTGAAAATTGTACTGCTGAAGGA ATGGTGTGCAACCATCTGTGTTCCAGTGATGGCTGTTGGGGACCTGGGCCAGACCAATGT CTGTCGTGTCGCCGCTTCAGTAGAGGAAGGATCTGCATAGAGTCTTGTAACCTCTATGAT GGTGAATTTCGGGAGTTTGAGAATGGCTCCATCTGTGTGGAGTGTGACCCCCAGTGTGAG AAGATGGAAGATGGCCTCCTCACATGCCATGGACCGGGTCCTGACAACTGTACAAAGTGC TCTCATTTTAAAGATGGCCCAAACTGTGTGGAAAAATGTCCAGATGGCTTACAGGGGGCA AACAGTTTCATTTTCAAGTATGCTGATCCAGATCGGGAGTGCCACCCATGCCATCCAAAC TGCACCCAAGGGTGTAACGGTCCCACTAGTCATGACTGCATTTACTACCCATGGACGGGC CATTCCACTTTACCACAACATGCTAGAACTCCCCTGATTGCAGCTGGAGTAATTGGTGGG CTCTTCATTCTGGTCATTGTGGGTCTGACATTTGCTGTTTATGTTAGAAGGAAGAGCATC AAAAAGAAAAGAGCCTTGAGAAGATTCTTGGAAACAGAGTTGGTGGAACCATTAACTCCC AGTGGCACAGCACCCAATCAAGCTCAACTTCGTATTTTGAAAGAAACTGAGCTGAAGAGG GTAAAAGTCCTTGGCTCAGGTGCTTTTGGAACGGTTTATAAAGGTATTTGGGTACCTGAA GGAGAAACTGTGAAGATTCCTGTGGCTATTAAGATTCTTAATGAGACAACTGGTCCCAAG GCAAATGTGGAGTTCATGGATGAAGCTCTGATCATGGCAAGTATGGATCATCCACACCTA GTCCGGTTGCTGGGTGTGTGTCTGAGCCCAACCATCCAGCTGGTTACTCAACTTATGCCC CATGGCTGCCTGTTGGAGTATGTCCACGAGCACAAGGATAACATTGGATCACAACTGCTG CTTAACTGGTGTGTCCAGATAGCTAAGGGAATGATGTACCTGGAAGAAAGACGACTCGTT CATCGGGATTTGGCAGCCCGTAATGTCTTAGTGAAATCTCCAAACCATGTGAAAATCACA GATTTTGGGCTAGCCAGACTCTTGGAAGGAGATGAAAAAGAGTACAATGCTGATGGAGGA AAGATGCCAATTAAATGGATGGCTCTGGAGTGTATACATTACAGGAAATTCACCCATCAG AGTGACGTTTGGAGCTATGGAGTTACTATATGGGAACTGATGACCTTTGGAGGAAAACCC TATGATGGAATTCCAACGCGAGAAATCCCTGATTTATTAGAGAAAGGAGAACGTTTGCCT CAGCCTCCCATCTGCACTATTGACGTTTACATGGTCATGGTCAAATGTTGGATGATTGAT GCTGACAGTAGACCTAAATTTAAGGAACTGGCTGCTGAGTTTTCAAGGATGGCTCGAGAC CCTCAAAGATACCTAGTTATTCAGGGTGATGATCGTATGAAGCTTCCCAGTCCAAATGAC AGCAAGTTCTTTCAGAATCTCTTGGATGAAGAGGATTTGGAAGATATGATGGATGCTGAG GAGTACTTGGTCCCTCAGGCTTTCAACATCCCACCTCCCATCTATACTTCCAGAGCAAGA ATTGACTCGAATAGGAACCAGTTTGTATACCGAGATGGAGGTTTTGCTGCTGAACAAGGA GTGTCTGTGCCCTACAGAGCCCCAACTAGCACAATTCCAGAAGCTCCTGTGGCACAGGGT GCTACTGCTGAGATTTTTGATGACTCCTGCTGTAATGGCACCCTACGCAAGCCAGTGGCA CCCCATGTCCAAGAGGACAGTAGCACCCAGAGGTACAGTGCTGACCCCACCGTGTTTGCC CCAGAACGGAGCCCACGAGGAGAGCTGGATGAGGAAGGTTACATGACTCCTATGCGAGAC AAACCCAAACAAGAATACCTGAATCCAGTGGAGGAGAACCCTTTTGTTTCTCGGAGAAAA AATGGAGACCTTCAAGCATTGGATAATCCCGAATATCACAATGCATCCAATGGTCCACCC AAGGCCGAGGATGAGTATGTGAATGAGCCACTGTACCTCAACACCTTTGCCAACACCTTG GGAAAAGCTGAGTACCTGAAGAACAACATACTGTCAATGCCAGAGAAGGCCAAGAAAGCG TTTGACAACCCTGACTACTGGAACCACAGCCTGCCACCTCGGAGCACCCTTCAGCACCCA GACTACCTGCAGGAGTACAGCACAAAATATTTTTATAAACAGAATGGGCGGATCCGGCCT ATTGTGGCAGAGAATCCTGAATACCTCTCTGAGTTCTCCCTGAAGCCAGGCACTGTGCTG CCGCCTCCACCTTACAGACACCGGAATACTGTGGTGTAA
- Chromosome Location
- 2
- Locus
- Not Available
- External Identifiers
Resource Link UniProtKB ID Q15303 UniProtKB Entry Name ERBB4_HUMAN HGNC ID HGNC:3432 - General References
- Plowman GD, Culouscou JM, Whitney GS, Green JM, Carlton GW, Foy L, Neubauer MG, Shoyab M: Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1746-50. [Article]
- Elenius K, Corfas G, Paul S, Choi CJ, Rio C, Plowman GD, Klagsbrun M: A novel juxtamembrane domain isoform of HER4/ErbB4. Isoform-specific tissue distribution and differential processing in response to phorbol ester. J Biol Chem. 1997 Oct 17;272(42):26761-8. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Culouscou JM, Plowman GD, Carlton GW, Green JM, Shoyab M: Characterization of a breast cancer cell differentiation factor that specifically activates the HER4/p180erbB4 receptor. J Biol Chem. 1993 Sep 5;268(25):18407-10. [Article]
- Plowman GD, Green JM, Culouscou JM, Carlton GW, Rothwell VM, Buckley S: Heregulin induces tyrosine phosphorylation of HER4/p180erbB4. Nature. 1993 Dec 2;366(6454):473-5. [Article]
- Cohen BD, Green JM, Foy L, Fell HP: HER4-mediated biological and biochemical properties in NIH 3T3 cells. Evidence for HER1-HER4 heterodimers. J Biol Chem. 1996 Mar 1;271(9):4813-8. [Article]
- Riese DJ 2nd, Bermingham Y, van Raaij TM, Buckley S, Plowman GD, Stern DF: Betacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin-beta. Oncogene. 1996 Jan 18;12(2):345-53. [Article]
- Elenius K, Paul S, Allison G, Sun J, Klagsbrun M: Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation. EMBO J. 1997 Mar 17;16(6):1268-78. [Article]
- Carraway KL 3rd, Weber JL, Unger MJ, Ledesma J, Yu N, Gassmann M, Lai C: Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases. Nature. 1997 May 29;387(6632):512-6. [Article]
- Komurasaki T, Toyoda H, Uchida D, Morimoto S: Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. Oncogene. 1997 Dec 4;15(23):2841-8. [Article]
- Zhang D, Sliwkowski MX, Mark M, Frantz G, Akita R, Sun Y, Hillan K, Crowley C, Brush J, Godowski PJ: Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9562-7. [Article]
- Fiddes RJ, Campbell DH, Janes PW, Sivertsen SP, Sasaki H, Wallasch C, Daly RJ: Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3. J Biol Chem. 1998 Mar 27;273(13):7717-24. [Article]
- Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE: ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases. J Biol Chem. 1999 Jun 11;274(24):17209-18. [Article]
- Elenius K, Choi CJ, Paul S, Santiestevan E, Nishi E, Klagsbrun M: Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase. Oncogene. 1999 Apr 22;18(16):2607-15. [Article]
- Harari D, Tzahar E, Romano J, Shelly M, Pierce JH, Andrews GC, Yarden Y: Neuregulin-4: a novel growth factor that acts through the ErbB-4 receptor tyrosine kinase. Oncogene. 1999 Apr 29;18(17):2681-9. [Article]
- Kainulainen V, Sundvall M, Maatta JA, Santiestevan E, Klagsbrun M, Elenius K: A natural ErbB4 isoform that does not activate phosphoinositide 3-kinase mediates proliferation but not survival or chemotaxis. J Biol Chem. 2000 Mar 24;275(12):8641-9. [Article]
- Rio C, Buxbaum JD, Peschon JJ, Corfas G: Tumor necrosis factor-alpha-converting enzyme is required for cleavage of erbB4/HER4. J Biol Chem. 2000 Apr 7;275(14):10379-87. [Article]
- Sweeney C, Lai C, Riese DJ 2nd, Diamonti AJ, Cantley LC, Carraway KL 3rd: Ligand discrimination in signaling through an ErbB4 receptor homodimer. J Biol Chem. 2000 Jun 30;275(26):19803-7. [Article]
- Garcia RA, Vasudevan K, Buonanno A: The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3596-601. [Article]
- Egeblad M, Mortensen OH, van Kempen LC, Jaattela M: BIBX1382BS, but not AG1478 or PD153035, inhibits the ErbB kinases at different concentrations in intact cells. Biochem Biophys Res Commun. 2001 Feb 16;281(1):25-31. [Article]
- Sartor CI, Zhou H, Kozlowska E, Guttridge K, Kawata E, Caskey L, Harrelson J, Hynes N, Ethier S, Calvo B, Earp HS 3rd: Her4 mediates ligand-dependent antiproliferative and differentiation responses in human breast cancer cells. Mol Cell Biol. 2001 Jul;21(13):4265-75. [Article]
- Komuro A, Nagai M, Navin NE, Sudol M: WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J Biol Chem. 2003 Aug 29;278(35):33334-41. Epub 2003 Jun 13. [Article]
- Li Y, Yu WH, Ren J, Chen W, Huang L, Kharbanda S, Loda M, Kufe D: Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein. Mol Cancer Res. 2003 Aug;1(10):765-75. [Article]
- Williams CC, Allison JG, Vidal GA, Burow ME, Beckman BS, Marrero L, Jones FE: The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone. J Cell Biol. 2004 Nov 8;167(3):469-78. [Article]
- Aqeilan RI, Donati V, Palamarchuk A, Trapasso F, Kaou M, Pekarsky Y, Sudol M, Croce CM: WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res. 2005 Aug 1;65(15):6764-72. [Article]
- Vidal GA, Naresh A, Marrero L, Jones FE: Presenilin-dependent gamma-secretase processing regulates multiple ERBB4/HER4 activities. J Biol Chem. 2005 May 20;280(20):19777-83. Epub 2005 Mar 3. [Article]
- Naresh A, Long W, Vidal GA, Wimley WC, Marrero L, Sartor CI, Tovey S, Cooke TG, Bartlett JM, Jones FE: The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells. Cancer Res. 2006 Jun 15;66(12):6412-20. [Article]
- Linggi B, Carpenter G: ErbB-4 s80 intracellular domain abrogates ETO2-dependent transcriptional repression. J Biol Chem. 2006 Sep 1;281(35):25373-80. Epub 2006 Jun 30. [Article]
- Maatta JA, Sundvall M, Junttila TT, Peri L, Laine VJ, Isola J, Egeblad M, Elenius K: Proteolytic cleavage and phosphorylation of a tumor-associated ErbB4 isoform promote ligand-independent survival and cancer cell growth. Mol Biol Cell. 2006 Jan;17(1):67-79. Epub 2005 Oct 26. [Article]
- Muraoka-Cook RS, Sandahl M, Husted C, Hunter D, Miraglia L, Feng SM, Elenius K, Earp HS 3rd: The intracellular domain of ErbB4 induces differentiation of mammary epithelial cells. Mol Biol Cell. 2006 Sep;17(9):4118-29. Epub 2006 Jul 12. [Article]
- Pitfield SE, Bryant I, Penington DJ, Park G, Riese DJ 2nd: Phosphorylation of ErbB4 on tyrosine 1056 is critical for ErbB4 coupling to inhibition of colony formation by human mammary cell lines. Oncol Res. 2006;16(4):179-93. [Article]
- Strunk KE, Husted C, Miraglia LC, Sandahl M, Rearick WA, Hunter DM, Earp HS 3rd, Muraoka-Cook RS: HER4 D-box sequences regulate mitotic progression and degradation of the nuclear HER4 cleavage product s80HER4. Cancer Res. 2007 Jul 15;67(14):6582-90. [Article]
- Li Z, Mei Y, Liu X, Zhou M: Neuregulin-1 only induces trans-phosphorylation between ErbB receptor heterodimer partners. Cell Signal. 2007 Mar;19(3):466-71. Epub 2006 Sep 15. [Article]
- Sundvall M, Peri L, Maatta JA, Tvorogov D, Paatero I, Savisalo M, Silvennoinen O, Yarden Y, Elenius K: Differential nuclear localization and kinase activity of alternative ErbB4 intracellular domains. Oncogene. 2007 Oct 18;26(48):6905-14. Epub 2007 May 7. [Article]
- Kaushansky A, Gordus A, Budnik BA, Lane WS, Rush J, MacBeath G: System-wide investigation of ErbB4 reveals 19 sites of Tyr phosphorylation that are unusually selective in their recruitment properties. Chem Biol. 2008 Aug 25;15(8):808-17. doi: 10.1016/j.chembiol.2008.07.006. [Article]
- Zeng F, Xu J, Harris RC: Nedd4 mediates ErbB4 JM-a/CYT-1 ICD ubiquitination and degradation in MDCK II cells. FASEB J. 2009 Jun;23(6):1935-45. doi: 10.1096/fj.08-121947. Epub 2009 Feb 4. [Article]
- Tvorogov D, Sundvall M, Kurppa K, Hollmen M, Repo S, Johnson MS, Elenius K: Somatic mutations of ErbB4: selective loss-of-function phenotype affecting signal transduction pathways in cancer. J Biol Chem. 2009 Feb 27;284(9):5582-91. doi: 10.1074/jbc.M805438200. Epub 2008 Dec 19. [Article]
- Li Y, Zhou Z, Alimandi M, Chen C: WW domain containing E3 ubiquitin protein ligase 1 targets the full-length ErbB4 for ubiquitin-mediated degradation in breast cancer. Oncogene. 2009 Aug 20;28(33):2948-58. doi: 10.1038/onc.2009.162. Epub 2009 Jun 29. [Article]
- Gilmore-Hebert M, Ramabhadran R, Stern DF: Interactions of ErbB4 and Kap1 connect the growth factor and DNA damage response pathways. Mol Cancer Res. 2010 Oct;8(10):1388-98. doi: 10.1158/1541-7786.MCR-10-0042. Epub 2010 Sep 21. [Article]
- Carrasco-Garcia E, Saceda M, Grasso S, Rocamora-Reverte L, Conde M, Gomez-Martinez A, Garcia-Morales P, Ferragut JA, Martinez-Lacaci I: Small tyrosine kinase inhibitors interrupt EGFR signaling by interacting with erbB3 and erbB4 in glioblastoma cell lines. Exp Cell Res. 2011 Jun 10;317(10):1476-89. doi: 10.1016/j.yexcr.2011.03.015. Epub 2011 Apr 1. [Article]
- Jones FE, Golding JP, Gassmann M: ErbB4 signaling during breast and neural development: novel genetic models reveal unique ErbB4 activities. Cell Cycle. 2003 Nov-Dec;2(6):555-9. [Article]
- Zaczek A, Brandt B, Bielawski KP: The diverse signaling network of EGFR, HER2, HER3 and HER4 tyrosine kinase receptors and the consequences for therapeutic approaches. Histol Histopathol. 2005 Jul;20(3):1005-15. [Article]
- Muraoka-Cook RS, Feng SM, Strunk KE, Earp HS 3rd: ErbB4/HER4: role in mammary gland development, differentiation and growth inhibition. J Mammary Gland Biol Neoplasia. 2008 Jun;13(2):235-46. doi: 10.1007/s10911-008-9080-x. Epub 2008 Apr 25. [Article]
- Jones FE: HER4 intracellular domain (4ICD) activity in the developing mammary gland and breast cancer. J Mammary Gland Biol Neoplasia. 2008 Jun;13(2):247-58. doi: 10.1007/s10911-008-9076-6. Epub 2008 May 13. [Article]
- Sundvall M, Iljin K, Kilpinen S, Sara H, Kallioniemi OP, Elenius K: Role of ErbB4 in breast cancer. J Mammary Gland Biol Neoplasia. 2008 Jun;13(2):259-68. doi: 10.1007/s10911-008-9079-3. Epub 2008 May 3. [Article]
- Xu Y, Li X, Liu X, Zhou M: Neuregulin-1/ErbB signaling and chronic heart failure. Adv Pharmacol. 2010;59:31-51. doi: 10.1016/S1054-3589(10)59002-1. [Article]
- Veikkolainen V, Vaparanta K, Halkilahti K, Iljin K, Sundvall M, Elenius K: Function of ERBB4 is determined by alternative splicing. Cell Cycle. 2011 Aug 15;10(16):2647-57. Epub 2011 Aug 15. [Article]
- Bouyain S, Longo PA, Li S, Ferguson KM, Leahy DJ: The extracellular region of ErbB4 adopts a tethered conformation in the absence of ligand. Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15024-9. Epub 2005 Oct 3. [Article]
- Wood ER, Shewchuk LM, Ellis B, Brignola P, Brashear RL, Caferro TR, Dickerson SH, Dickson HD, Donaldson KH, Gaul M, Griffin RJ, Hassell AM, Keith B, Mullin R, Petrov KG, Reno MJ, Rusnak DW, Tadepalli SM, Ulrich JC, Wagner CD, Vanderwall DE, Waterson AG, Williams JD, White WL, Uehling DE: 6-Ethynylthieno[3,2-d]- and 6-ethynylthieno[2,3-d]pyrimidin-4-anilines as tunable covalent modifiers of ErbB kinases. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2773-8. doi: 10.1073/pnas.0708281105. Epub 2008 Feb 19. [Article]
- Qiu C, Tarrant MK, Choi SH, Sathyamurthy A, Bose R, Banjade S, Pal A, Bornmann WG, Lemmon MA, Cole PA, Leahy DJ: Mechanism of activation and inhibition of the HER4/ErbB4 kinase. Structure. 2008 Mar;16(3):460-7. doi: 10.1016/j.str.2007.12.016. [Article]
- Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]
- Takahashi Y, Fukuda Y, Yoshimura J, Toyoda A, Kurppa K, Moritoyo H, Belzil VV, Dion PA, Higasa K, Doi K, Ishiura H, Mitsui J, Date H, Ahsan B, Matsukawa T, Ichikawa Y, Moritoyo T, Ikoma M, Hashimoto T, Kimura F, Murayama S, Onodera O, Nishizawa M, Yoshida M, Atsuta N, Sobue G, Fifita JA, Williams KL, Blair IP, Nicholson GA, Gonzalez-Perez P, Brown RH Jr, Nomoto M, Elenius K, Rouleau GA, Fujiyama A, Morishita S, Goto J, Tsuji S: ERBB4 mutations that disrupt the neuregulin-ErbB4 pathway cause amyotrophic lateral sclerosis type 19. Am J Hum Genet. 2013 Nov 7;93(5):900-5. doi: 10.1016/j.ajhg.2013.09.008. Epub 2013 Oct 10. [Article]
Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB08916 Afatinib approved yes inhibitor Details DB12267 Brigatinib approved, investigational unknown inhibitor Details DB12010 Fostamatinib approved, investigational unknown inhibitor Details DB15035 Zanubrutinib approved, investigational unknown inhibitor Details