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Protein Page:
HER2 (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
HER2 a proto-oncogenic receptor tyrosine kinase of the EGFR family. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. Not activated by EGF, TGF- alpha and amphiregulin. Amplified in breast cancer. Overexpression induces constitutive activity, and the gene is amplified or overexpressed in up to 30% of breast cancers, correlating with poor survival. The antibody Herceptin is approved for treatment of metastatic breast cancer with HER2 amplification/overexpression. Somatic mutations seen in 4% of lung cancers and also in breast, gastric, ovarian cancer and glioblastoma. One SNP shows predisposition to breast and gastric cancer. Inhibitors: Herceptin, lapatinib, PKI-166, EKB-569, CI-1033. Note: This description may include information from UniProtKB.
Protein type: Oncoprotein; Kinase, protein; Protein kinase, tyrosine (receptor); Protein kinase, TK; EC 2.7.10.1; Membrane protein, integral; TK group; EGFR family
Chromosomal Location of Human Ortholog: 17q12
Cellular Component: apical plasma membrane; basolateral plasma membrane; cytoplasm; cytoplasmic vesicle; endosome membrane; integral to membrane; myelin sheath; nucleus; perinuclear region of cytoplasm; plasma membrane; receptor complex
Molecular Function: ATP binding; ErbB-3 class receptor binding; growth factor binding; identical protein binding; phosphatidylinositol-4,5-bisphosphate 3-kinase activity; protein binding; protein C-terminus binding; protein dimerization activity; protein heterodimerization activity; protein phosphatase binding; protein-tyrosine kinase activity; Ras guanyl-nucleotide exchange factor activity; receptor signaling protein tyrosine kinase activity; transmembrane receptor activity; transmembrane receptor protein tyrosine kinase activity
Biological Process: cell proliferation; cell surface receptor linked signal transduction; enzyme linked receptor protein signaling pathway; heart development; MAPKKK cascade; motor axon guidance; myelination; negative regulation of immature T cell proliferation in the thymus; neuromuscular junction development; oligodendrocyte differentiation; peptidyl-tyrosine phosphorylation; peripheral nervous system development; phosphoinositide 3-kinase cascade; phosphoinositide phosphorylation; phosphoinositide-mediated signaling; positive regulation of cell adhesion; positive regulation of cell growth; positive regulation of epithelial cell proliferation; positive regulation of GTPase activity; positive regulation of MAP kinase activity; positive regulation of protein amino acid phosphorylation; positive regulation of transcription from RNA polymerase I promoter; positive regulation of transcription from RNA polymerase III promoter; positive regulation of translation; protein amino acid autophosphorylation; protein amino acid phosphorylation; regulation of angiogenesis; regulation of microtubule-based process; regulation of phosphoinositide 3-kinase cascade; signal transduction; transcription, DNA-dependent; transmembrane receptor protein tyrosine kinase signaling pathway; wound healing
Disease: Gastric Cancer; Glioma Susceptibility 1; Lung Cancer
Reference #:  P04626 (UniProtKB)
Gene Symbols: ERBB2
Molecular weight: 137,910 Da
Basal Isoelectric point: 5.58  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

HER2

Protein Structure Not Found.
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Substrate Sequence Logo
Sequence Logo

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Sites Implicated In
cell adhesion, altered: Y1023‑p, Y1139‑p
cell growth, altered: Y877‑p, Y1023‑p, Y1139‑p, Y1221‑p, Y1222‑p
cell motility, altered: Y1139‑p, Y1196‑p, Y1221‑p, Y1222‑p, Y1248‑p
cytoskeletal reorganization: Y1248‑p
signaling pathway regulation: Y1139‑p, Y1196‑p, Y1222‑p, Y1248‑p
transcription, induced: Y1139‑p, Y1196‑p, Y1222‑p, Y1248‑p
activity, induced: Y1248‑p
activity, inhibited: Y1023‑p
enzymatic activity, induced: Y1196‑p, Y1221‑p, Y1222‑p
enzymatic activity, inhibited: T686‑p
intracellular localization: T686‑p, Y1248‑p
molecular association, regulation: Y735‑p, Y923‑p, Y1005‑p, Y1023‑p, Y1112‑p, Y1139‑p, Y1196‑p, Y1222‑p, Y1248‑p
phosphorylation: T686‑p, Y1248‑p
protein degradation: Y1112‑p
receptor desensitization, altered: T1172‑p
receptor internalization, altered: T686‑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 K150‑ub RSLTEILkGGVLIQR
0 1 K175‑ub LWKDIFHkNNQLALt
0 1 T182‑p kNNQLALtLIDTNRS
6 1 T686‑p QQKIRKYtMRRLLQE
0 34 T701‑p TELVEPLtPsGAMPN
0 2 S703‑p LVEPLtPsGAMPNQA
0 2 K724‑ub ETELRKVkVLGSGAF
0 8 T733‑p LGSGAFGtVykGIWI
1 147 Y735‑p SGAFGtVykGIWIPD
0 2 K736‑ub GAFGtVykGIWIPDG
0 2 K747‑ub IPDGENVkIPVAIkV
0 1 K753‑ub VkIPVAIkVLRENTS
0 4 Y772‑p KEILDEAyVMAGVGS
0 9 T875‑p RLLDIDEtEyHADGG
19 112 Y877‑p LDIDEtEyHADGGKV
0 1 K887‑ub DGGKVPIkWMALESI
1 0 T900‑p SILRRRFtHQSDVWS
1 1 Y923‑p MTFGAKPyDGIPARE
0 7 S998‑p NEDLGPAsPLDstFy
0 8 S1002‑p GPAsPLDstFyRsLL
0 3 T1003‑p PAsPLDstFyRsLLE
1 75 Y1005‑p sPLDstFyRsLLEDD
0 1 S1007‑p LDstFyRsLLEDDDM
7 35 Y1023‑p DLVDAEEyLVPQQGF
0 3 S1049‑p MVHHRHRssstRsGG
0 5 S1050‑p VHHRHRssstRsGGG
0 6 S1051‑p HHRHRssstRsGGGD
0 2 T1052‑p HRHRssstRsGGGDL
0 18 S1054‑p HRssstRsGGGDLtL
0 1 T1060‑p RsGGGDLtLGLEPsE
0 2 S1066‑p LtLGLEPsEEEAPRS
0 4 S1078‑p PRSPLAPsEGAGsDV
0 8 S1083‑p APsEGAGsDVFDGDL
0 3 S1100‑p GAAKGLQsLPtHDPs
0 2 T1103‑p KGLQsLPtHDPsPLQ
0 8 S1107‑p sLPtHDPsPLQRySE
6 2 Y1112‑p DPsPLQRySEDPTVP
1 0 S1113 PsPLQRySEDPTVPL
0 1 S1122‑p DPTVPLPsEtDGyVA
0 1 T1124‑p TVPLPsEtDGyVAPL
0 12 Y1127‑p LPsEtDGyVAPLtCs
0 2 T1132‑p DGyVAPLtCsPQPEy
0 5 S1134‑p yVAPLtCsPQPEyVN
11 47 Y1139‑p tCsPQPEyVNQPDVR
0 49 S1151‑p DVRPQPPsPREGPLP
0 6 T1166‑p AARPAGAtLERPKtL
1 1 T1172‑p AtLERPKtLsPGKNG
1 6 S1174‑p LERPKtLsPGKNGVV
9 7 Y1196‑p GAVENPEyLtPQGGA
0 1 T1198‑p VENPEyLtPQGGAAP
0 3 S1214‑p PHPPPAFsPAFDNLy
22 15 Y1221‑p sPAFDNLyyWDQDPP
26 9 Y1222‑p PAFDNLyyWDQDPPE
0 1 S1235‑p PERGAPPstFKGtPt
0 1 T1236‑p ERGAPPstFKGtPtA
0 10 T1240‑p PPstFKGtPtAENPE
0 2 T1242‑p stFKGtPtAENPEyL
47 194 Y1248‑p PtAENPEyLGLDVPV
2241 : Phospho-HER2/ErbB2 (Tyr877) Antibody
6942 : Phospho-HER2/ErbB2 (Tyr1196) (D66B7) Rabbit mAb
2243 : Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb
2249 : Phospho-HER2/ErbB2 (Tyr1221/1222) Antibody
2243 : Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb
2249 : Phospho-HER2/ErbB2 (Tyr1221/1222) Antibody
2244 : Phospho-HER2/ErbB2 (Tyr1248)/EGFR (Tyr1173) Antibody
2247 : Phospho-HER2/ErbB2 (Tyr1248) Antibody
  HER2 iso2  
- gap
- gap
- gap
T76 QQKIRKYTMRRLLQE
T91 TELVEPLTPSGAMPN
S93 LVEPLTPSGAMPNQA
K114 ETELRKVKVLGSGAF
T123 LGSGAFGTVYKGIWI
Y125 SGAFGTVYKGIWIPD
K126 GAFGTVYKGIWIPDG
K137 IPDGENVKIPVAIKV
K143 VKIPVAIKVLRENTS
Y162 KEILDEAYVMAGVGS
T265 RLLDIDETEYHADGG
Y267 LDIDETEYHADGGKV
K277 DGGKVPIKWMALESI
T290 SILRRRFTHQSDVWS
Y313 MTFGAKPYDGIPARE
S388 NEDLGPASPLDSTFY
S392 GPASPLDSTFYRSLL
T393 PASPLDSTFYRSLLE
Y395 SPLDSTFYRSLLEDD
S397 LDSTFYRSLLEDDDM
Y413 DLVDAEEYLVPQQGF
S439 MVHHRHRSSSTRSGG
S440 VHHRHRSSSTRSGGG
S441 HHRHRSSSTRSGGGD
T442 HRHRSSSTRSGGGDL
S444 HRSSSTRSGGGDLTL
T450 RSGGGDLTLGLEPSE
S456 LTLGLEPSEEEAPRS
S468 PRSPLAPSEGAGSDV
S473 APSEGAGSDVFDGDL
S490 GAAKGLQSLPTHDPS
T493 KGLQSLPTHDPSPLQ
S497 SLPTHDPSPLQRYSE
Y502 DPSPLQRYSEDPTVP
S503 PSPLQRYSEDPTVPL
S512 DPTVPLPSETDGYVA
T514 TVPLPSETDGYVAPL
Y517 LPSETDGYVAPLTCS
T522 DGYVAPLTCSPQPEY
S524 YVAPLTCSPQPEYVN
Y529 TCSPQPEYVNQPDVR
S541 DVRPQPPSPREGPLP
T556 AARPAGATLERPKTL
T562 ATLERPKTLSPGKNG
S564 LERPKTLSPGKNGVV
Y586 GAVENPEYLTPQGGA
T588 VENPEYLTPQGGAAP
S604 PHPPPAFSPAFDNLY
Y611 SPAFDNLYYWDQDPP
Y612 PAFDNLYYWDQDPPE
S625 PERGAPPSTFKGTPT
T626 ERGAPPSTFKGTPTA
T630 PPSTFKGTPTAENPE
T632 STFKGTPTAENPEYL
Y638 PTAENPEYLGLDVPV
2241 : Phospho-HER2/ErbB2 (Tyr877) Antibody
6942 : Phospho-HER2/ErbB2 (Tyr1196) (D66B7) Rabbit mAb
2243 : Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb
2249 : Phospho-HER2/ErbB2 (Tyr1221/1222) Antibody
2243 : Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb
2249 : Phospho-HER2/ErbB2 (Tyr1221/1222) Antibody
2244 : Phospho-HER2/ErbB2 (Tyr1248)/EGFR (Tyr1173) Antibody
2247 : Phospho-HER2/ErbB2 (Tyr1248) Antibody
  HER2 iso5  
K120 RSLTEILKGGVLIQR
K145 LWKDIFHKNNQLALT
T152 KNNQLALTLIDTNRS
T656 QQKIRKYTMRRLLQE
T671 TELVEPLTPSGAMPN
S673 LVEPLTPSGAMPNQA
K694 ETELRKVKVLGSGAF
T703 LGSGAFGTVYKGIWI
Y705 SGAFGTVYKGIWIPD
K706 GAFGTVYKGIWIPDG
K717 IPDGENVKIPVAIKV
K723 VKIPVAIKVLRENTS
Y742 KEILDEAYVMAGVGS
T845 RLLDIDETEYHADGG
Y847 LDIDETEYHADGGKV
K857 DGGKVPIKWMALESI
T870 SILRRRFTHQSDVWS
Y893 MTFGAKPYDGIPARE
S968 NEDLGPASPLDSTFY
S972 GPASPLDSTFYRSLL
T973 PASPLDSTFYRSLLE
Y975 SPLDSTFYRSLLEDD
S977 LDSTFYRSLLEDDDM
Y993 DLVDAEEYLVPQQGF
S1019 MVHHRHRSSSTRSGG
S1020 VHHRHRSSSTRSGGG
S1021 HHRHRSSSTRSGGGD
T1022 HRHRSSSTRSGGGDL
S1024 HRSSSTRSGGGDLTL
T1030 RSGGGDLTLGLEPSE
S1036 LTLGLEPSEEEAPRS
S1048 PRSPLAPSEGAGSDV
S1053 APSEGAGSDVFDGDL
S1070 GAAKGLQSLPTHDPS
T1073 KGLQSLPTHDPSPLQ
S1077 SLPTHDPSPLQRYSE
Y1082 DPSPLQRYSEDPTVP
S1083 PSPLQRYSEDPTVPL
S1092 DPTVPLPSETDGYVA
T1094 TVPLPSETDGYVAPL
Y1097 LPSETDGYVAPLTCS
T1102 DGYVAPLTCSPQPEY
S1104 YVAPLTCSPQPEYVN
Y1109 TCSPQPEYVNQPDVR
S1121 DVRPQPPSPREGPLP
T1136 AARPAGATLERPKTL
T1142 ATLERPKTLSPGKNG
S1144 LERPKTLSPGKNGVV
Y1166 GAVENPEYLTPQGGA
T1168 VENPEYLTPQGGAAP
S1184 PHPPPAFSPAFDNLY
Y1191 SPAFDNLYYWDQDPP
Y1192 PAFDNLYYWDQDPPE
S1205 PERGAPPSTFKGTPT
T1206 ERGAPPSTFKGTPTA
T1210 PPSTFKGTPTAENPE
T1212 STFKGTPTAENPEYL
Y1218 PTAENPEYLGLDVPV
2241 : Phospho-HER2/ErbB2 (Tyr877) Antibody
6942 : Phospho-HER2/ErbB2 (Tyr1196) (D66B7) Rabbit mAb
2243 : Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb
2249 : Phospho-HER2/ErbB2 (Tyr1221/1222) Antibody
2243 : Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb
2249 : Phospho-HER2/ErbB2 (Tyr1221/1222) Antibody
2244 : Phospho-HER2/ErbB2 (Tyr1248)/EGFR (Tyr1173) Antibody
2247 : Phospho-HER2/ErbB2 (Tyr1248) Antibody
  mouse

 
K151 RSLTEILKGGVLIRG
K176 LWKDVLRKNNQLAPV
V183 KNNQLAPVDMDTNRS
T687‑p RQKIRKYtMRRLLQE
T702‑p TELVEPLtPsGAVPN
S704‑p LVEPLtPsGAVPNQA
K725‑ub ETELRKLkVLGSGAF
T734 LGSGAFGTVyKGIWI
Y736‑p SGAFGTVyKGIWIPD
K737 GAFGTVyKGIWIPDG
K748‑ub IPDGENVkIPVAIKV
K754 VkIPVAIKVLRENTS
Y773 KEILDEAYVMAGVGS
T876 RLLDIDETEyHADGG
Y878‑p LDIDETEyHADGGKV
K888 DGGKVPIKWMALESI
T901 SILRRRFTHQSDVWS
Y924‑p MTFGAKPyDGIPARE
S999 NEDLGPSSPMDSTFY
S1003 GPSSPMDSTFYRSLL
T1004 PSSPMDSTFYRSLLE
Y1006 SPMDSTFYRSLLEDD
S1008 MDSTFYRSLLEDDDM
Y1024 ELVDAEEYLVPQQGF
S1050 TAHRRHRSSSARSGG
S1051 AHRRHRSSSARSGGG
S1052 HRRHRSSSARSGGGE
A1053 RRHRSSSARSGGGEL
S1055 HRSSSARSGGGELTL
T1061 RSGGGELTLGLEPSE
S1067 LTLGLEPSEEEPPRS
S1079 PRSPLAPSEGAGsDV
S1084‑p APSEGAGsDVFDGDL
S1101 GVTKGLQSLSPHDLS
P1104 KGLQSLSPHDLSPLQ
S1108 SLSPHDLSPLQRysE
Y1113‑p DLSPLQRysEDPTLP
S1114‑p LSPLQRysEDPTLPL
P1123 DPTLPLPPETDGYVA
T1125 TLPLPPETDGYVAPL
Y1128 LPPETDGYVAPLACS
A1133 DGYVAPLACSPQPEY
S1135 YVAPLACSPQPEYVN
Y1140 ACSPQPEYVNQPEVR
L1152 EVRPQSPLTPEGPPP
T1167 PIRPAGATLERPKtL
T1173‑p ATLERPKtLsPGKNG
S1175‑p LERPKtLsPGKNGVV
Y1197‑p GAVENPEyLAPRAGT
A1199 VENPEyLAPRAGTAS
S1215 PHPSPAFSPAFDNLy
Y1222‑p SPAFDNLyyWDQNSS
Y1223‑p PAFDNLyyWDQNSSE
S1236 SEQGPPPSTFEGTPT
T1237 EQGPPPSTFEGTPTA
T1241 PPSTFEGTPTAENPE
T1243 STFEGTPTAENPEyL
Y1249‑p PTAENPEyLGLDVPV
2241 : Phospho-HER2/ErbB2 (Tyr877) Antibody
6942 : Phospho-HER2/ErbB2 (Tyr1196) (D66B7) Rabbit mAb
2243 : Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb
2249 : Phospho-HER2/ErbB2 (Tyr1221/1222) Antibody
2243 : Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb
2249 : Phospho-HER2/ErbB2 (Tyr1221/1222) Antibody
2244 : Phospho-HER2/ErbB2 (Tyr1248)/EGFR (Tyr1173) Antibody
2247 : Phospho-HER2/ErbB2 (Tyr1248) Antibody
  rat

 
K151 RSLTEILKGGVLIRG
K176 LWKDVFRKNNQLAPV
V183 KNNQLAPVDIDTNRS
T688‑p RQKIRKYtMRRLLQE
T703 TELVEPLTPSGAMPN
S705 LVEPLTPSGAMPNQA
K726 ETELRKVKVLGSGAF
T735 LGSGAFGTVYKGIWI
Y737 SGAFGTVYKGIWIPD
K738 GAFGTVYKGIWIPDG
K749 IPDGENVKIPVAIKV
K755 VKIPVAIKVLRENTS
Y774 KEILDEAYVMAGVGS
T877 RLLDIDETEyHADGG
Y879‑p LDIDETEyHADGGKV
K889 DGGKVPIKWMALESI
T902 SILRRRFTHQSDVWS
Y925 MTFGAKPYDGIPARE
S1000 NEDLGPSSPMDSTFY
S1004 GPSSPMDSTFYRSLL
T1005 PSSPMDSTFYRSLLE
Y1007 SPMDSTFYRSLLEDD
S1009 MDSTFYRSLLEDDDM
Y1025‑p DLVDAEEyLVPQQGF
S1051 TAHRRHRSSSTRsGG
S1052 AHRRHRSSSTRsGGG
S1053 HRRHRSSSTRsGGGE
T1054 RRHRSSSTRsGGGEL
S1056‑p HRSSSTRsGGGELTL
T1062 RsGGGELTLGLEPSE
S1068 LTLGLEPSEEGPPRS
S1080‑p PRSPLAPsEGAGsDV
S1085‑p APsEGAGsDVFDGDL
S1102 GVTKGLQSLSPHDLS
P1105 KGLQSLSPHDLSPLQ
S1109 SLSPHDLSPLQRySE
Y1114‑p DLSPLQRySEDPTLP
S1115 LSPLQRySEDPTLPL
P1124 DPTLPLPPETDGYVA
T1126 TLPLPPETDGYVAPL
Y1129 LPPETDGYVAPLACS
A1134 DGYVAPLACSPQPEy
S1136 YVAPLACSPQPEyVN
Y1141‑p ACSPQPEyVNQSEVQ
L1153 EVQPQPPLTPEGPLP
T1168 PVRPAGATLERPKTL
T1174 ATLERPKTLsPGKNG
S1176‑p LERPKTLsPGKNGVV
Y1198‑p GAVENPEyLVPREGT
V1200 VENPEyLVPREGTAS
S1216 PHPSPAFSPAFDNLy
Y1223‑p SPAFDNLyyWDQNSS
Y1224‑p PAFDNLyyWDQNSSE
S1237 SEQGPPPSNFEGTPT
N1238 EQGPPPSNFEGTPTA
T1242 PPSNFEGTPTAENPE
T1244 SNFEGTPTAENPEyL
Y1250‑p PTAENPEyLGLDVPV
2241 : Phospho-HER2/ErbB2 (Tyr877) Antibody
2247 : Phospho-HER2/ErbB2 (Tyr1248) Antibody
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