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Protein Page:
HER4 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
HER4 a receptor tyrosine kinase of the EGFR family. Specifically binds and is activated by neuregulins, NRG- 2, NRG-3, heparin-binding EGF-like growth factor, betacellulin and NTAK. Heterodimerizes and signals with other EGF receptors. Interaction with these factors induces cell differentiation. Not activated by EGF, TGF-A, and amphiregulin. Interacts with PDZ domains of DLG2, DLG3, DLG4 and the syntrophin SNTB2. Interacts with WWOX. May act as a tumor suppressor: overexpressed in head and neck cancer , but downregulated in renal cancer, papillary carcinoma, high-grade gliomas and invasive breast cancer. 3 alternatively-spliced isoforms of the human protein have been reported. Note: This description may include information from UniProtKB.
Protein type: Protein kinase, TK; EC 2.7.10.1; Protein kinase, tyrosine (receptor); Membrane protein, integral; Kinase, protein; TK group; EGFR family
Chromosomal Location of Human Ortholog: 2q33.3-q34
Cellular Component: basolateral plasma membrane; cytosol; extracellular region; integral to membrane; mitochondrial matrix; mitochondrion; nucleoplasm; nucleus; plasma membrane; receptor complex
Molecular Function: ATP binding; epidermal growth factor receptor binding; phosphatidylinositol-4,5-bisphosphate 3-kinase activity; protein binding; protein homodimerization activity; protein-tyrosine kinase activity; Ras guanyl-nucleotide exchange factor activity; receptor signaling protein tyrosine kinase activity; transmembrane receptor protein tyrosine kinase activity
Biological Process: cell fate commitment; cell migration; cell proliferation; central nervous system morphogenesis; embryonic pattern specification; heart development; lactation; MAPKKK cascade; mitochondrial fragmentation during apoptosis; negative regulation of apoptosis; negative regulation of cell proliferation; nervous system development; neural crest cell migration; olfactory bulb interneuron differentiation; peptidyl-tyrosine phosphorylation; phosphoinositide phosphorylation; phosphoinositide-mediated signaling; positive regulation of cardiac muscle cell proliferation; positive regulation of cell proliferation; positive regulation of GTPase activity; positive regulation of phosphoinositide 3-kinase activity; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of protein amino acid phosphorylation; positive regulation of transcription, DNA-dependent; positive regulation of tyrosine phosphorylation of Stat5 protein; protein amino acid autophosphorylation; regulation of cell migration; regulation of phosphoinositide 3-kinase cascade; signal transduction; transcription, DNA-dependent; transmembrane receptor protein tyrosine kinase signaling pathway
Disease: Amyotrophic Lateral Sclerosis 19
Reference #:  Q15303 (UniProtKB)
Gene Symbols: ERBB4
Molecular weight: 146,808 Da
Basal Isoelectric point: 5.98  Predict pI for various phosphorylation states
CST Pathways:  ErbB/HER Signaling  |  Tyrosine Kinases & Substrates
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

HER4

Protein Structure Not Found.
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Sites Implicated In
cell growth, altered: Y1056‑p
activity, induced: Y1056‑p
molecular association, regulation: Y733‑p, Y875‑p, Y984‑p, Y1022‑p, Y1035‑p, Y1056‑p, Y1081‑p, Y1128‑p, Y1150‑p, Y1162‑p, Y1188‑p, Y1202‑p, Y1208‑p, Y1221‑p, Y1242‑p, Y1258‑p, Y1268‑p, Y1284‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 LTP 

LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 HTP 

HTP: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
0 1 T692 ALRRFLETELVEPLt
0 10 T699‑p TELVEPLtPSGTAPN
0 1 S701 LVEPLtPSGTAPNQA
0 2 T703 EPLtPSGTAPNQAQL
0 6 T731‑p LGSGAFGtVyKGIWV
1 146 Y733‑p SGAFGtVyKGIWVPE
0 3 K745‑ub VPEGETVkIPVAIKI
0 1 K873‑ac RLLEGDEkEyNADGG
0 7 Y875‑p LEGDEkEyNADGGkM
0 1 K881‑ac EyNADGGkMPIKWMA
1 0 Y984‑p MARDPQRyLVIQGDD
0 1 S997 DDRMKLPSPNDSKFF
1 0 Y1022‑p DMMDAEEyLVPQAFN
0 1 Y1035‑p FNIPPPIyTSRARID
3 2 Y1056‑p GHSPPPAyTPMSGNQ
0 1 Y1066‑p MSGNQFVyRDGGFAA
0 1 Y1081‑p EQGVSVPyRAPTSTI
0 2 Y1128‑p EDSSTQRySADPTVF
0 1 S1140‑p TVFAPERsPRGELDE
0 5 Y1150‑p GELDEEGyMTPMRDK
0 3 T1152 LDEEGyMTPMRDKPK
2 2 Y1162‑p RDKPKQEyLNPVEEN
2 1 Y1188‑p QALDNPEyHNASNGP
1 2 Y1202‑p PPKAEDEyVNEPLyL
1 2 Y1208‑p EyVNEPLyLNTFANT
1 1 Y1221‑p NTLGKAEyLKNNILS
2 3 Y1242‑p KAFDNPDyWNHSLPP
0 4 Y1258‑p STLQHPDyLQEySTk
0 2 Y1262‑p HPDyLQEySTkyFyK
0 1 K1265‑ub yLQEySTkyFyKQNG
0 1 Y1266‑p LQEySTkyFyKQNGR
1 1 Y1268‑p EySTkyFyKQNGRIR
5 7 Y1284‑p IVAENPEyLSEFSLK
0 1 Y1301‑p TVLPPPPyRHRNTVV
3790 : Phospho-HER4/ErbB4 (Tyr984) Antibody
4757 : Phospho-HER4/ErbB4 (Tyr1284) (21A9) Rabbit mAb
  HER4 iso2  
T682 ALRRFLETELVEPLT
T689 TELVEPLTPSGTAPN
S691 LVEPLTPSGTAPNQA
T693 EPLTPSGTAPNQAQL
T721 LGSGAFGTVYKGIWV
Y723 SGAFGTVYKGIWVPE
K735 VPEGETVKIPVAIKI
K863 RLLEGDEKEYNADGG
Y865 LEGDEKEYNADGGKM
K871 EYNADGGKMPIKWMA
Y974 MARDPQRYLVIQGDD
S987 DDRMKLPSPNDSKFF
Y1012 DMMDAEEYLVPQAFN
Y1025 FNIPPPIYTSRARID
Y1046 GHSPPPAYTPMSGNQ
Y1056 MSGNQFVYRDGGFAA
Y1071 EQGVSVPYRAPTSTI
Y1118 EDSSTQRYSADPTVF
S1130 TVFAPERSPRGELDE
Y1140 GELDEEGYMTPMRDK
T1142 LDEEGYMTPMRDKPK
Y1152 RDKPKQEYLNPVEEN
Y1178 QALDNPEYHNASNGP
Y1192 PPKAEDEYVNEPLYL
Y1198 EYVNEPLYLNTFANT
Y1211 NTLGKAEYLKNNILS
Y1232 KAFDNPDYWNHSLPP
Y1248 STLQHPDYLQEYSTK
Y1252 HPDYLQEYSTKYFYK
K1255 YLQEYSTKYFYKQNG
Y1256 LQEYSTKYFYKQNGR
Y1258 EYSTKYFYKQNGRIR
Y1274 IVAENPEYLSEFSLK
Y1291 TVLPPPPYRHRNTVV
3790 : Phospho-HER4/ErbB4 (Tyr984) Antibody
  HER4 iso3  
T692 ALRRFLETELVEPLT
T699 TELVEPLTPSGTAPN
S701 LVEPLTPSGTAPNQA
T703 EPLTPSGTAPNQAQL
T731 LGSGAFGTVYKGIWV
Y733 SGAFGTVYKGIWVPE
K745 VPEGETVKIPVAIKI
K873 RLLEGDEKEYNADGG
Y875 LEGDEKEYNADGGKM
K881 EYNADGGKMPIKWMA
Y984 MARDPQRYLVIQGDD
S997 DDRMKLPSPNDSKFF
Y1022 DMMDAEEYLVPQAFN
Y1035 FNIPPPIYTSRARID
- gap
Y1050 SNRNQFVYRDGGFAA
Y1065 EQGVSVPYRAPTSTI
Y1112 EDSSTQRYSADPTVF
S1124 TVFAPERSPRGELDE
Y1134 GELDEEGYMTPMRDK
T1136 LDEEGYMTPMRDKPK
Y1146 RDKPKQEYLNPVEEN
Y1172 QALDNPEYHNASNGP
Y1186 PPKAEDEYVNEPLYL
Y1192 EYVNEPLYLNTFANT
Y1205 NTLGKAEYLKNNILS
Y1226 KAFDNPDYWNHSLPP
Y1242 STLQHPDYLQEYSTK
Y1246 HPDYLQEYSTKYFYK
K1249 YLQEYSTKYFYKQNG
Y1250 LQEYSTKYFYKQNGR
Y1252 EYSTKYFYKQNGRIR
Y1268 IVAENPEYLSEFSLK
Y1285 TVLPPPPYRHRNTVV
3790 : Phospho-HER4/ErbB4 (Tyr984) Antibody
  HER4 iso4  
T682 ALRRFLETELVEPLT
T689 TELVEPLTPSGTAPN
S691 LVEPLTPSGTAPNQA
T693 EPLTPSGTAPNQAQL
T721 LGSGAFGTVYKGIWV
Y723 SGAFGTVYKGIWVPE
K735 VPEGETVKIPVAIKI
K863 RLLEGDEKEYNADGG
Y865 LEGDEKEYNADGGKM
K871 EYNADGGKMPIKWMA
Y974 MARDPQRYLVIQGDD
S987 DDRMKLPSPNDSKFF
Y1012 DMMDAEEYLVPQAFN
Y1025 FNIPPPIYTSRARID
- gap
Y1040 SNRNQFVYRDGGFAA
Y1055 EQGVSVPYRAPTSTI
Y1102 EDSSTQRYSADPTVF
S1114 TVFAPERSPRGELDE
Y1124 GELDEEGYMTPMRDK
T1126 LDEEGYMTPMRDKPK
Y1136 RDKPKQEYLNPVEEN
Y1162 QALDNPEYHNASNGP
Y1176 PPKAEDEYVNEPLYL
Y1182 EYVNEPLYLNTFANT
Y1195 NTLGKAEYLKNNILS
Y1216 KAFDNPDYWNHSLPP
Y1232 STLQHPDYLQEYSTK
Y1236 HPDYLQEYSTKYFYK
K1239 YLQEYSTKYFYKQNG
Y1240 LQEYSTKYFYKQNGR
Y1242 EYSTKYFYKQNGRIR
Y1258 IVAENPEYLSEFSLK
Y1275 TVLPPPPYRHRNTVV
3790 : Phospho-HER4/ErbB4 (Tyr984) Antibody
  mouse

 
T692‑p ALRRFLEtELVEPLt
T699‑p tELVEPLtPsGtAPN
S701‑p LVEPLtPsGtAPNQA
T703‑p EPLtPsGtAPNQAQL
T731 LGSGAFGTVyKGIWV
Y733‑p SGAFGTVyKGIWVPE
K745‑ub VPEGETVkIPVAIKI
K873 RLLEGDEKEYNADGG
Y875 LEGDEKEYNADGGKM
K881 EYNADGGKMPIKWMA
Y984 MARDPQRYLVIQGDD
S997‑p DDRMKLPsPNDSKFF
Y1022 DMMDAEEYLVPQAFN
Y1035 FNIPPPIYTSRTRID
Y1056 GHSPPPAYTPMSGNQ
Y1066 MSGNQFVYQDGGFAT
Y1081 QQGMPMPYRATTSTI
Y1128 EDSSTQRYSADPTVF
N1140 TVFAPERNPRGELDE
Y1150‑p GELDEEGyMtPMHDK
T1152‑p LDEEGyMtPMHDKPK
Y1162‑p HDKPKQEyLNPVEEN
Y1188 QALDNPEYHSASSGP
Y1202 PPKAEDEYVNEPLYL
Y1208 EYVNEPLYLNTFANA
Y1221 NALGSAEYMKNSVLS
Y1242 KAFDNPDYWNHSLPP
Y1258 STLQHPDYLQEYSTK
Y1262 HPDYLQEYSTKYFYK
K1265 YLQEYSTKYFYKQNG
Y1266 LQEYSTKYFYKQNGR
Y1268 EYSTKYFYKQNGRIR
Y1284‑p IVAENPEyLSEFSLK
Y1301 TMLPPPPYRHRNTVV
3790 : Phospho-HER4/ErbB4 (Tyr984) Antibody
4757 : Phospho-HER4/ErbB4 (Tyr1284) (21A9) Rabbit mAb
  rat

 
T692 ALRRFLETELVEPLT
T699 TELVEPLTPSGTAPN
S701 LVEPLTPSGTAPNQA
T703 EPLTPSGTAPNQAQL
T731 LGSGAFGTVYKGIWV
Y733 SGAFGTVYKGIWVPE
K745 VPEGETVKIPVAIKI
K873 RLLEGDEKEYNADGG
Y875 LEGDEKEYNADGGKM
K881 EYNADGGKMPIKWMA
Y984 MARDPQRYLVIQGDD
S997 DDRMKLPSPNDSKFF
Y1022 DMMDAEEYLVPQAFN
Y1035 FNIPPPIYTSRTRID
Y1056 GHSPPPAYTPMSGSQ
Y1066 MSGSQFVYQDGGFAT
Y1081 QQGMPMPYTATTSTI
Y1128 EDSSTQRYSADPTVF
N1140 TVFAPERNPRAELDE
Y1150 AELDEEGYMTPMHDK
T1152 LDEEGYMTPMHDKPK
Y1162 HDKPKQEYLNPVEEN
Y1188 QALDNPEYHSASSGP
Y1202 PPKAEDEYVNEPLYL
Y1208 EYVNEPLYLNTFTNA
Y1221 NALGNAEYMKNSLLS
Y1242 KAFDNPDYWNHSLPP
Y1258 STLQHPDYLQEYSTK
Y1262 HPDYLQEYSTKYFYK
K1265 YLQEYSTKYFYKQNG
Y1266 LQEYSTKYFYKQNGR
Y1268 EYSTKYFYKQNGRIR
Y1284‑p IVAENPEyLSEFSLK
Y1301 TMLPPPPYRHRNTVV
3790 : Phospho-HER4/ErbB4 (Tyr984) Antibody
4757 : Phospho-HER4/ErbB4 (Tyr1284) (21A9) Rabbit mAb
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