ERBB4;HER4

Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)]

Homo sapiens (Human)

146808

1308

Pending Verification

Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)]

Amyotrophic lateral sclerosis 19 (ALS19) [MIM:615515]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269|PubMed:24119685}. Note=The disease is caused by mutations affecting the gene represented in this entry.

MUTAGEN 646 646 Q->C: Constitutively activated kinase. {ECO:0000269|PubMed:17120616}.; MUTAGEN 675 675 V->A: Abolishes proteolytic processing and nuclear localization. {ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:17638867}.; MUTAGEN 681 684 KKKR->EIMG: Abolishes nuclear localization of the ERBB4 intracellular domain. {ECO:0000269|PubMed:15534001}.; MUTAGEN 710 710 L->N: Strongly reduced autophosphorylation. {ECO:0000269|PubMed:18287036}.; MUTAGEN 721 721 V->I: No effect on kinase activity. {ECO:0000269|PubMed:19098003}.; MUTAGEN 751 751 K->R: Abolishes kinase activity. Abolishes phosphorylation, proteolytic processing and nuclear localization. {ECO:0000269|PubMed:11390655, ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867}.; MUTAGEN 766 766 M->R: Strongly reduced autophosphorylation. {ECO:0000269|PubMed:18287036}.; MUTAGEN 773 773 A->S: No effect on kinase activity. {ECO:0000269|PubMed:19098003}.; MUTAGEN 782 782 R->Q: No effect on kinase activity. {ECO:0000269|PubMed:19098003}.; MUTAGEN 810 810 E->K: No effect on kinase activity. {ECO:0000269|PubMed:19098003}.; MUTAGEN 843 843 D->N: Loss of kinase activity. {ECO:0000269|PubMed:16978839}.; MUTAGEN 854 854 P->Q: No effect on kinase activity. {ECO:0000269|PubMed:19098003}.; MUTAGEN 861 861 D->Y: Loss of kinase activity. {ECO:0000269|PubMed:19098003}.; MUTAGEN 864 864 L->R: Strongly reduced autophosphorylation. {ECO:0000269|PubMed:18287036}.; MUTAGEN 872 872 E->K: No effect on kinase activity. {ECO:0000269|PubMed:19098003}.; MUTAGEN 926 926 T->M: No effect on kinase activity. {ECO:0000269|PubMed:19098003}.; MUTAGEN 947 947 I->R: Constitutively autophosphorylated. {ECO:0000269|PubMed:18287036}.; MUTAGEN 992 992 R->A: Abolishes APC/C-mediated degradation; when associated with A-995 and A-1000. {ECO:0000269|PubMed:17638867}.; MUTAGEN 995 995 L->A: Abolishes APC/C-mediated degradation; when associated with A-992 and A-1000. {ECO:0000269|PubMed:17638867}.; MUTAGEN 1000 1000 D->A: Abolishes APC/C-mediated degradation; when associated with A-992 and A-995. {ECO:0000269|PubMed:17638867}.; MUTAGEN 1035 1035 Y->A: No effect on interaction with WWOX. Abolishes interaction with WWOX; when associated with A-1301. {ECO:0000269|PubMed:16061658}.; MUTAGEN 1056 1056 Y->A: Abolishes interaction with NEDD4 and impairs ubiquitination. Promotes nuclear translocation of ERBB4 intracellular domain E4ICD1. {ECO:0000269|PubMed:19561640}.; MUTAGEN 1056 1056 Y->F: Abolishes interaction with WWP1; when associated with F-1301. {ECO:0000269|PubMed:19561640}.; MUTAGEN 1301 1301 Y->A: Abolishes interaction with NEDD4 and impairs ubiquitination. {ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:16061658, ECO:0000269|PubMed:19561640}.; MUTAGEN 1301 1301 Y->A: No effect on interaction with WWOX. Abolishes interaction with WWOX; when associated with A-1035. Loss of interaction with YAP1 and stimulation of transcription. {ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:16061658, ECO:0000269|PubMed:19561640}.; MUTAGEN 1301 1301 Y->F: Abolishes interaction with WWP1; when associated with F-1056. {ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:16061658, ECO:0000269|PubMed:19561640}.

MKPATGLWVWVSLLVAAGTVQPSDSQSVCAGTENKLSSLSDLEQQYRALRKYYENCEVVMGNLEITSIEHNRDLSFLRSVREVTGYVLVALNQFRYLPLENLRIIRGTKLYEDRYALAIFLNYRKDGNFGLQELGLKNLTEILNGGVYVDQNKFLCYADTIHWQDIVRNPWPSNLTLVSTNGSSGCGRCHKSCTGRCWGPTENHCQTLTRTVCAEQCDGRCYGPYVSDCCHRECAGGCSGPKDTDCFACMNFNDSGACVTQCPQTFVYNPTTFQLEHNFNAKYTYGAFCVKKCPHNFVVDSSSCVRACPSSKMEVEENGIKMCKPCTDICPKACDGIGTGSLMSAQTVDSSNIDKFINCTKINGNLIFLVTGIHGDPYNAIEAIDPEKLNVFRTVREITGFLNIQSWPPNMTDFSVFSNLVTIGGRVLYSGLSLLILKQQGITSLQFQSLKEISAGNIYITDNSNLCYYHTINWTTLFSTINQRIVIRDNRKAENCTAEGMVCNHLCSSDGCWGPGPDQCLSCRRFSRGRICIESCNLYDGEFREFENGSICVECDPQCEKMEDGLLTCHGPGPDNCTKCSHFKDGPNCVEKCPDGLQGANSFIFKYADPDRECHPCHPNCTQGCNGPTSHDCIYYPWTGHSTLPQHARTPLIAAGVIGGLFILVIVGLTFAVYVRRKSIKKKRALRRFLETELVEPLTPSGTAPNQAQLRILKETELKRVKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLSPTIQLVTQLMPHGCLLEYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDVYMVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDRMKLPSPNDSKFFQNLLDEEDLEDMMDAEEYLVPQAFNIPPPIYTSRARIDSNRSEIGHSPPPAYTPMSGNQFVYRDGGFAAEQGVSVPYRAPTSTIPEAPVAQGATAEIFDDSCCNGTLRKPVAPHVQEDSSTQRYSADPTVFAPERSPRGELDEEGYMTPMRDKPKQEYLNPVEENPFVSRRKNGDLQALDNPEYHNASNGPPKAEDEYVNEPLYLNTFANTLGKAEYLKNNILSMPEKAKKAFDNPDYWNHSLPPRSTLQHPDYLQEYSTKYFYKQNGRIRPIVAENPEYLSEFSLKPGTVLPPPPYRHRNTVV

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:10348342, ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10722704, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:11178955, ECO:0000269|PubMed:11390655, ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001, ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:16251361, ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:8617750, ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115, ECO:0000269|PubMed:9334263}.

Active site (1); Alternative sequence (2); Beta strand (58); Binding site (1); Chain (2); Compositional bias (2); Disulfide bond (23); Domain (1); Glycosylation (11); Helix (32); Modified residue (10); Motif (5); Mutagenesis (26); Natural variant (4); Nucleotide binding (3); Signal peptide (1); Topological domain (2); Transmembrane (1); Turn (7); 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 expressed in cerebellum, but only the isoform JM-B is expressed in the heart. {ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:9334263}.

Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)]

Recombinant

HEK293

Lyophilized

7.4-7.5

Sterile-filtered colorless solution

1mg/ml

Standard

PBS

SDS-PAGE

> 98%

RP-HPLC

-20°C

This bioreagent is stable at 4°C (short-term) and -70°C(long-term). After reconstitution, sample may be stored at 4°C for 2-7 days and below -18°C for future use.

Reconstitute in sterile distilled H2O to no less than 100ug/ml; dilute reconstituted stock further in other aqueous solutions if needed. Please review COA for lot-specific instructions. Final measurements should be determined by the end-user for optimal performance.