|ERBB2_HUMAN » Receptor tyrosine-protein kinase erbB-2 » p185erbB2;C-erbB-2;NEU proto-oncogene;Tyrosine kinase-type cell surface receptor HER2;MLN 19;|
|Hydrophobic Thickness||34.0 ± 1.8 Å|
|Tilt Angle||0 ± 1°|
|Links||UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB|
|TM Segments||650-675 (650-680)|
Adherens junction (KEGG)
Bladder cancer (KEGG)
Calcium signaling pathway (KEGG)
Developmental Biology (Reactome)
Endometrial cancer (KEGG)
ErbB signaling pathway (KEGG)
Focal adhesion (KEGG)
HIF-1 signaling pathway (KEGG)
Immune System (Reactome)
Non-small cell lung cancer (KEGG)
Pancreatic cancer (KEGG)
Pathways in cancer (KEGG)
Prostate cancer (KEGG)
Proteoglycans in cancer (KEGG)
Signal Transduction (Reactome)
|PDB||2a91 (22-530), 3pp0 (703-1009), 3rcd (A/B/C/D=713-1028), 3h3b (A/B=23-214), 1s78 (A/B=23-646), 2jwa (A/B=641-684), 4hrm (A/C=24-219), 3n85 (A=23-646), 3be1 (A=23-646), 3mzw (A=23-646), 2ks1 (A=641-684), 2l4k (B=1135-1144), 1mw4 (B=1135-1144), 1mfg (B=1247-1255), 1mfl (B=1247-1255), 4hrn (C/D=529-625), 1qr1 (C/F=654-662), 1n8z (C=23-629), 4hrl (C=24-219), 4gfu (F=1246-1252)|
|OPM||1iij (RAT), 1n8y (RAT), 2jwa, 2ks1|
CI174, Complex: CI174:ERBB2
DHB3, Complex: DHB3:ERBB2
EGFR, Complex: P3C2B:P3C2A:EGFR:ERBB2
MMP16, Complex: MMP16:ERBB2
PTPRK, Complex: PTPRK:ERBB2
PTPRO, Complex: ERBB2:PTPRO
|UniProt annotation for ERBB2_HUMAN » Receptor tyrosine-protein kinase erbB-2|
|FUNCTION: Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5"-TCAAATTC-3" sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Activated by dimerization. Not activated by EGF, TGF-alpha and amphiregulin. Interaction with PTK6 increases its intrinsic kinase activity. SUBUNIT: Homodimer. Heterodimer with EGFR, ERBB3 and ERBB4. Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1196. Interacts with PRKCABP and PLXNB1. Interacts (when phosphorylated on Tyr-1248) with MEMO1. Interacts with MUC1; the interaction is enhanced by heregulin (HRG). Interacts (when phosphorylated on Tyr-1139) with GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1248) with ERBB2IP. Interacts with KPNB1, RANBP2, EEA1, CRM1, CLTC, PTK6, RPA94 and ACTB. Interacts with SRC and MYOC (By similarity). TISSUE SPECIFICITY: Expressed in a variety of tumor tissues including primary breast tumors and tumors from small bowel, esophagus, kidney and mouth. DISEASE: Hereditary diffuse gastric cancer (HDGC) OMIM: A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Note=The gene represented in this entry is involved in disease pathogenesis. DISEASE: Glioma (GLM) OMIM: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. Note=The gene represented in this entry is involved in disease pathogenesis. DISEASE: Ovarian cancer (OC) OMIM: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. DISEASE: Lung cancer (LNCR) OMIM: A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Note=The gene represented in this entry is involved in disease pathogenesis. DISEASE: Gastric cancer (GASC) OMIM: A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. Note=The gene represented in this entry is involved in disease pathogenesis. DISEASE: Note=Chromosomal aberrations involving ERBB2 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to truncated CDK12 protein not in-frame with ERBB2.|
|UniProt features for ERBB2_HUMAN » Receptor tyrosine-protein kinase erbB-2|
SIGNAL 1 22 Potential. |
CHAIN 23 1255 Receptor tyrosine-protein kinase erbB-2.
DOMAIN 720 987 Protein kinase.
REGION 676 689 Nuclear localization signal.
REGION 676 689 Required for interaction with KPNB1 and EEA1.
REGION 1195 1197 Interaction with PIK3C2B (Probable).
ACT_SITE 845 845 Proton acceptor (By similarity).
DISULFID 26 53
DISULFID 162 192
DISULFID 195 204
DISULFID 199 212
DISULFID 220 227
DISULFID 224 235
DISULFID 236 244
DISULFID 240 252
DISULFID 255 264
DISULFID 268 295
DISULFID 299 311
DISULFID 315 331
DISULFID 334 338
DISULFID 342 367
DISULFID 475 504
DISULFID 511 520
DISULFID 515 528
DISULFID 531 540
DISULFID 544 560
DISULFID 563 576
DISULFID 567 584
DISULFID 587 596
DISULFID 600 623
DISULFID 626 634 By similarity.
DISULFID 630 642 By similarity.
|Amino Acid Sequence for ERBB2_HUMAN » Receptor tyrosine-protein kinase erbB-2|
|MELAALCRWG LLLALLPPGA ASTQVCTGTD MKLRLPASPE THLDMLRHLY QGCQVVQGNL ELTYLPTNAS LSFLQDIQEV QGYVLIAHNQ VRQVPLQRLR IVRGTQLFED NYALAVLDNG DPLNNTTPVT GASPGGLREL QLRSLTEILK GGVLIQRNPQ LCYQDTILWK DIFHKNNQLA LTLIDTNRSR ACHPCSPMCK GSRCWGESSE DCQSLTRTVC AGGCARCKGP LPTDCCHEQC AAGCTGPKHS DCLACLHFNH SGICELHCPA LVTYNTDTFE SMPNPEGRYT FGASCVTACP YNYLSTDVGS CTLVCPLHNQ EVTAEDGTQR CEKCSKPCAR VCYGLGMEHL REVRAVTSAN IQEFAGCKKI FGSLAFLPES FDGDPASNTA PLQPEQLQVF ETLEEITGYL YISAWPDSLP DLSVFQNLQV IRGRILHNGA YSLTLQGLGI SWLGLRSLRE LGSGLALIHH NTHLCFVHTV PWDQLFRNPH QALLHTANRP EDECVGEGLA CHQLCARGHC WGPGPTQCVN CSQFLRGQEC VEECRVLQGL PREYVNARHC LPCHPECQPQ NGSVTCFGPE ADQCVACAHY KDPPFCVARC PSGVKPDLSY MPIWKFPDEE GACQPCPINC THSCVDLDDK GCPAEQRASP LTSIISAVVG ILLVVVLGVV FGILIKRRQQ KIRKYTMRRL LQETELVEPL TPSGAMPNQA QMRILKETEL RKVKVLGSGA FGTVYKGIWI PDGENVKIPV AIKVLRENTS PKANKEILDE AYVMAGVGSP YVSRLLGICL TSTVQLVTQL MPYGCLLDHV RENRGRLGSQ DLLNWCMQIA KGMSYLEDVR LVHRDLAARN VLVKSPNHVK ITDFGLARLL DIDETEYHAD GGKVPIKWMA LESILRRRFT HQSDVWSYGV TVWELMTFGA KPYDGIPARE IPDLLEKGER LPQPPICTID VYMIMVKCWM IDSECRPRFR ELVSEFSRMA RDPQRFVVIQ NEDLGPASPL DSTFYRSLLE DDDMGDLVDA EEYLVPQQGF FCPDPAPGAG GMVHHRHRSS STRSGGGDLT LGLEPSEEEA PRSPLAPSEG AGSDVFDGDL GMGAAKGLQS LPTHDPSPLQ RYSEDPTVPL PSETDGYVAP LTCSPQPEYV NQPDVRPQPP SPREGPLPAA RPAGATLERP KTLSPGKNGV VKDVFAFGGA VENPEYLTPQ GGAAPQPHPP PAFSPAFDNL YYWDQDPPER GAPPSTFKGT PTAENPEYLG LDVPV|