Erbb4
entrez
59323
canonical
uniprot
Q62956
canonical
ensembl
ENSRNOG00000014248
resolver
ensp
ENSRNOP00000092095
resolver
ensp
ENSRNOP00000092891
resolver
ensp
ENSRNOP00000097510
resolver
enst
ENSRNOT00000100527
resolver
enst
ENSRNOT00000103925
resolver
enst
ENSRNOT00000118754
resolver
genesymbol
Erbb4
resolver
genesymbol_syn
Tyro-2
resolver
uniprot
A0A8I6AGX1
resolver
uniprot
A0A8I6AIL0
resolver
uniprot
A0A8I6GMJ5
resolver
uniprot
Q6UA28
resolver
uniprot
Q6UA29
resolver
uniprot
Q9Z2N7
resolver
uniprot_entry
A0A8I6AGX1_RAT
resolver
uniprot_entry
A0A8I6AIL0_RAT
resolver
uniprot_entry
A0A8I6GMJ5_RAT
resolver
uniprot_entry
ERBB4_RAT
resolver
uniprot_sec
Q6UA28
resolver
uniprot_sec
Q6UA29
resolver
uniprot_sec
Q9Z2N7
resolver
activity_regulation
ACTIVITY REGULATION: Binding of a cognate ligand leads to dimerization and activation by autophosphorylation on tyrosine residues. In vitro kinase activity is increased by Mg(2+) (By similarity). {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MKLATGLWVWGSLLVAARTVQPSASQSVCAGTENKLSSLSDLEQQYRALRKYYENCEVVMGNLEITSIEHNRDLSFLRSIREVTGYVLVALNQFRYLPLENLRIIRGTKLYEDRYALAIFLNYRKDGNFGLQELGLKNLTEILNGGVYVDQNKFLCYADTIHWQDIVRNPWPSNMTLVSTIGSSGCGRCHKSCTGRCWGPTENHCQTLTRTVCAEQCDGRCYGPYVSDCCHRECAGGCSGPKDTDCFACMNFNDSGACVTQCPQTFVYNPTTFQLEHNFNAKYTYGAFCVKKCPHNFVVDSSSCVRACPSSKMEVEENGIKMCKPCTDICPKACDGIGTGSLMSAQTVDSSNIDKFINCTKINGNLIFLVTGIHGDPYNAIDAIDPEKLNVFRTVREITGFLNIQTWPPNMTDFSVFSNLVTIGGRVLYSGLSLLILKQQGITSLQFQSLKEISAGNIYITDNSNLCYYHTINWTTLFSTVNQRIVIRDNRRAENCTAEGMVCNHLCSNDGCWGPGPDQCLSCRRFSRGKICIESCNLYDGEFREFENGSICVECDSQCEKMEDGLLTCHGPGPDNCTKCSHFKDGPNCVEKCPDVLQGANSFIFKYADQDRECHPCHPNCTQGCNGPTSHDCIYYPWTGHSTLPQHARTPLIAAGVIGGLFILVIMALTFAVYVRRKSIKKKRALRRFLETELVEPLTPSGTAPNQAQLRILKETELKRVKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASVDHPHLVRLLGVCLSPTIQLVTQLMPHGCLLEYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYIVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDRMKLPSPNDSKFFQNLLDEEDLEDMMDAEEYLVPQAFNIPPPIYTSRTRIDSNRSEIGHSPPPAYTPMSGSQFVYQDGGFATQQGMPMPYTATTSTIPEAPVAQGATAEMFDDSCCNGTLRKPVVPHVQEDSSTQRYSADPTVFAPERNPRAELDEEGYMTPMHDKPKQEYLNPVEENPFVSRRKNGDLQALDNPEYHSASSGPPKAEDEYVNEPLYLNTFTNALGNAEYMKNSLLSVPEKAKKAFDNPDYWNHSLPPRSTLQHPDYLQEYSTKYFYKQNGRIRPIVAENPEYLSEFSLKPGTMLPPPPYRHRNTVV
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
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. {ECO:0000269|PubMed:10839362, ECO:0000269|PubMed:12716924, ECO:0000269|PubMed:14654373, ECO:0000269|PubMed:17250808, ECO:0000269|PubMed:17521571}.
uniprot
proteins
mass_dalton
146958
uniprot
proteins
post_translational_modification
PTM: Isoform JM-A CYT-2 and isoform JM-A CYT-1 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, which are further processed by a presenilin-dependent gamma-secretase to release the respective cytoplasmic intracellular domain E4ICD (either E4ICD1/s80Cyt1 or E4ICD2/s80Cyt2) (By similarity). {ECO:0000250}.; PTM: Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Ligands trigger phosphorylation at specific tyrosine residues, thereby creating binding sites for scaffold proteins and effectors. Constitutively phosphorylated at a basal level when overexpressed in heterologous systems; ligand binding leads to increased phosphorylation. Phosphorylation at Tyr-1035 is important for interaction with STAT1. Phosphorylation at Tyr-1056 is important for interaction with PIK3R1. Phosphorylation at Tyr-1242 is important for interaction with SHC1. Phosphorylation at Tyr-1188 may also contribute to the interaction with SHC1. 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 (By similarity). {ECO:0000250}.; PTM: Ubiquitinated. During mitosis, the ERBB4 intracellular domain is ubiquitinated by the APC/C complex and targeted to proteasomal degradation. 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 (By similarity). {ECO:0000250}.
uniprot
proteins
protein_family
EGF receptor subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10839362
uniprot
proteins
pubmed
12716924
uniprot
proteins
pubmed
14654373
uniprot
proteins
pubmed
15355992
uniprot
proteins
pubmed
17250808
uniprot
proteins
pubmed
17521571
uniprot
proteins
pubmed
2025425
uniprot
proteins
pubmed
9030624
uniprot
proteins
pubmed
9553078
uniprot
proteins
sequence_length
1308
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12716924, ECO:0000269|PubMed:17250808}; Single-pass type I membrane protein {ECO:0000269|PubMed:12716924, ECO:0000269|PubMed:17250808}. Note=In response to NRG1 treatment, the activated receptor is internalized.; SUBCELLULAR LOCATION: [ERBB4 intracellular domain]: Nucleus {ECO:0000250}. Mitochondrion {ECO:0000250}. 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 derived from processing of isoform JM-A CYT-2 colocalizes with YAP1 in the nucleus (By similarity). {ECO:0000250}.
uniprot
proteins
transmembrane_region
TRANSMEM 652..675; /evidence="ECO:0000255
uniprot
proteins