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
Functions
ATP 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 activity
Processes
activation 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 pathway
Components
basolateral 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
ResourceLink
UniProtKB IDQ15303
UniProtKB Entry NameERBB4_HUMAN
HGNC IDHGNC:3432
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08916AfatinibapprovedyesinhibitorDetails
DB12267Brigatinibapproved, investigationalunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB15035Zanubrutinibapproved, investigationalunknowninhibitorDetails