Product: HER4 Antibody
Catalog: AF6445
Description: Rabbit polyclonal antibody to HER4
Application: WB IHC IF/ICC
Reactivity: Human, Mouse, Rat
Prediction: Horse, Sheep, Rabbit, Dog, Chicken, Xenopus
Mol.Wt.: kDa; 147kD(Calculated).
Uniprot: Q15303
RRID: AB_2835269

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 100ul $280 In stock
 200ul $350 In stock

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Product Info

WB 1:500-1000, IHC 1:50-1:200, IF/ICC 1:100-1:500
*The optimal dilutions should be determined by the end user.

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Horse(100%), Sheep(100%), Rabbit(100%), Dog(100%), Chicken(100%), Xenopus(89%)
HER4 Antibody detects endogenous levels of total HER4.
Cite Format: Affinity Biosciences Cat# AF6445, RRID:AB_2835269.
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.


4ICD; ALS19; Avian erythroblastic leukemia viral oncogene homolog 4; Avian erythroblastic leukemia viral v erb b2 oncogene homolog 4; E4ICD; EC; Erbb4; ERBB4 intracellular domain; ERBB4_HUMAN; HER 4; HER4; human epidermal growth factor receptor 4; Mer4; MGC138404; Oncogene ERBB4; p180erbB4; Proto-oncogene-like protein c-ErbB-4; Receptor protein tyrosine kinase erbB 4 precursor; Receptor tyrosine protein kinase erbB 4; s80HER4; Tyrosine kinase type cell surface receptor HER4; Tyrosine kinase-type cell surface receptor HER4; v erb a avian erythroblastic leukemia viral oncogene homolog like 4; v erb a erythroblastic leukemia viral oncogene homolog 4; v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian); V-ERB-B2 avian erythroblastic leukemia viral oncogene homolog 4; Verba avian erythroblastic leukemia viral oncogene homolog like 4; Verba erythroblastic leukemia viral oncogene homolog 4; VERBB2;



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.

The HER4/ERBB4 gene is a member of the type I receptor tyrosine kinase subfamily that includes EGFR (MIM 131550), ERBB2 (MIM 164870), and ERBB3 (MIM 190151). It encodes a receptor for NDF/heregulin (MIM 142445).



Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - Q15303 As Substrate

Site PTM Type Enzyme
N138 N-Glycosylation
Y157 Phosphorylation
S173 Phosphorylation
N174 N-Glycosylation
S183 Phosphorylation
N253 N-Glycosylation
N358 N-Glycosylation
N410 N-Glycosylation
N473 N-Glycosylation
N495 N-Glycosylation
N576 N-Glycosylation
T699 Phosphorylation
K714 Ubiquitination
K722 Ubiquitination
S726 Phosphorylation
T731 Phosphorylation
Y733 Phosphorylation
K745 Ubiquitination
K852 Ubiquitination
K858 Ubiquitination
K873 Acetylation
Y875 Phosphorylation Q15303 (ERBB4)
K881 Acetylation
K935 Ubiquitination
Y984 Phosphorylation
Y1022 Phosphorylation
Y1035 Phosphorylation Q15303 (ERBB4)
Y1056 Phosphorylation Q15303 (ERBB4)
Y1066 Phosphorylation
Y1081 Phosphorylation
Y1128 Phosphorylation
S1140 Phosphorylation
Y1150 Phosphorylation Q15303 (ERBB4)
Y1162 Phosphorylation Q15303 (ERBB4)
Y1188 Phosphorylation Q15303 (ERBB4)
Y1202 Phosphorylation Q15303 (ERBB4)
Y1208 Phosphorylation
Y1221 Phosphorylation
Y1242 Phosphorylation Q15303 (ERBB4)
Y1258 Phosphorylation Q15303 (ERBB4)
Y1262 Phosphorylation
K1265 Ubiquitination
Y1266 Phosphorylation
Y1268 Phosphorylation
Y1284 Phosphorylation Q15303 (ERBB4)
Y1301 Phosphorylation

PTMs - Q15303 As Enzyme

Substrate Site Source
Q15303 (ERBB4) Y875 Uniprot
Q15303 (ERBB4) Y1035 Uniprot
Q15303 (ERBB4) Y1056 Uniprot
Q15303 (ERBB4) Y1150 Uniprot
Q15303 (ERBB4) Y1162 Uniprot
Q15303 (ERBB4) Y1188 Uniprot
Q15303 (ERBB4) Y1202 Uniprot
Q15303 (ERBB4) Y1242 Uniprot
Q15303 (ERBB4) Y1258 Uniprot
Q15303 (ERBB4) Y1284 Uniprot

Research Backgrounds


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.


Isoform JM-A CYT-1 and isoform JM-A CYT-2 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 (m80HER4), which are further processed by a presenilin-dependent gamma-secretase to release a cytoplasmic intracellular domain (E4ICD; E4ICD1/s80Cyt1 or E4ICD2/s80Cyt2, depending on the isoform). Membrane-anchored 80 kDa fragments of the processed isoform JM-A CYT-1 are more readily degraded by the proteasome than fragments of isoform JM-A CYT-2, suggesting a prevalence of E4ICD2 over E4ICD1. Isoform JM-B CYT-1 and isoform JM-B CYT-2 lack the ADAM17 cleavage site and are not processed by ADAM17, precluding further processing by gamma-secretase.

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.

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.

Subcellular Location:

Cell membrane>Single-pass type I membrane protein.
Note: In response to NRG1 treatment, the activated receptor is internalized.

Nucleus. Mitochondrion.
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 colocalizes with YAP1 in the nucleus.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
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 CYT-1 and isoform JM-B CYT-1 are expressed in cerebellum, but only the isoform JM-B is expressed in the heart.

Subunit Structure:

Monomer in the absence of bound ligand. Homodimer or heterodimer with another ERBB family member upon ligand binding, thus forming heterotetramers. Interacts with EGFR and ERBB2. Interacts with CBFA2T3 (By similarity). Interacts with DLG2 (via its PDZ domain), DLG3 (via its PDZ domain), DLG4 (via its PDZ domain) and SNTB2 (via its PDZ domain). Interacts with MUC1. Interacts (via its PPxy motifs) with WWOX. Interacts (via the PPxY motif 3 of isoform JM-A CYT-2) with YAP1 (via the WW domain 1 of isoform 1). Interacts (isoform JM-A CYT-1 and isoform JM-B CYT-1) with WWP1. Interacts (via its intracellular domain) with TRIM28. Interacts (via the intracellular domains of both CYT-1 and CYT-2 isoforms) with KAP1; the interaction does not phosphorylate KAP1 but represses ERBB4-mediated transcriptional activity. Interacts with PRPU, DDX23, MATR3, RBM15, ILF3, KAP1, U5S1, U2SURP, ITCH, HNRNPU, AP2A1, NULC, LEO1, WWP2, IGHG1, HXK1, GRB7 AND ARS2. Interacts (phosphorylated isoform JM-A CYT-1 and isoform JM-B CYT-1) with PIK3R1. Interacts with SHC1. Interacts with GRB2. Interacts (soluble intracellular domain) with STAT5A. Interacts (soluble intracellular domain) with BCL2. Interacts (phosphorylated) with STAT1.


Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.

Research Fields

· Environmental Information Processing > Signal transduction > MAPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > ErbB signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Calcium signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > PI3K-Akt signaling pathway.   (View pathway)

· Human Diseases > Cancers: Overview > Proteoglycans in cancer.

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